biochem s2 Flashcards

Question

are metabolic pathways reversible or irreversible

Answer 1

irreversible

Answer 2

(Hexokinase is an enzyme thats phosphorylates glucose , fructose and mannose)

Answer 3

The end product (feedback inhibition ) goes back and can bind to the allosteric site on the enzyme and cause inhibition of the enzyme (this occurs hexokinase)

Answer 4

Control of flux is based on the amount of key enzymes and the presence of tissue specific isoenzymes and their regulation once made

Answer 5

1-Gene regulation This is a slower form of control as it required additional copies of the enzyme to be produced.It can enhance the amount of final product 2-End product feedback inhibition This is quick, if the end product is not rapidly used then the complete pathway is slowed as the first enzyme is inhibited

Answer 6

Glucose structure=hexose sugar with an aldehyde group at position 1.All of the hydroxyl groups are then on the right apart from position 3 which is flipped to the left hand side

Answer 7

-glucose cant cross the membrane by itself -It uses transport proteins to move from high to a low conc -Doesn't require energy -Phosphorylation prevents the glucose from returning

Answer 8

-A non protein component of an enzyme is called the cofactor -If the cofactor is organic its called a coenzyme -Coenzymes are derived from vitamins -Their role is to deliver chemical groups or atoms (hydrogen ions /phosphate)to and from the active site -The coenzyme nicotinamide adenine dinucleotide is involved in the transfer of protons -The coenzyme adenosine triphosphate (ATP)is involved in the transfer of phosphate groups

Answer 9

-loss of electrons -gain of oxygen -loss of hydrogen -results in many c-o bonds -results in compounds with lower potential energy

Answer 10

-Gain of electrons -loss of oxygen -gain of hydrogen -results in many c-h bonds -results in compounds woth higher potential energy

Answer 11

-Dehydrogenase means it is an oxidation step in which an aldehyde is converted to a carboxylic acid

Answer 12

endergonic

Answer 13

enderogonic

Answer 14

Glycolysis is where the 6 carbon molecule is broken down into pyruvate to extract energy The complete oxidation of glucose has a =-2834 kJ/mol of free energy that can be used to meet the cells energy requirements

Answer 15

The whole 2834 is not released as heat due to : 1-biological systems cant utilise heat as a source of energy 2-No single reaction of metabolism requires this amount of energy to be released in one step 3-Always needing to overcome the activation energy.Enzymes are capable of effecting only small changes when they catalyse reactions , releasing energy in steps This is why during the catabolism of glucose the molecule is broken down in small steps and energy is released in small amounts in the form of chemical energy with ATP being the energy carrier

Answer 16

2 pyruvate 2 ATP 2 NADH and 2H+

Answer 17

-has a 3 carbon backbone that fatty acids attach to -metabolized readily into an intermediate in glycolysis , dihydroxyacetone phosphate , which may be converted into pyruvic acid -Dihydroxyacetone may be used in gluconeogenesis to make glucose-6-phosphate for glucose to the blood

Answer 18

-kinases phosphorylates enzymes

Answer 19

-phosphatases dephosphorylates substrates

Answer 20

-2 ATPs used to prime glycolysis -4 ATPs produced from the glycolytic pathway as a result of substrate level phosphorylation (step 7+10) -2 NADHs generated -8 ATPs net gained from the conversion of glucose to pyruvate and the re-oxidation of the 2 NADHs produced

Answer 21

-series of 10 reactions that extract energy from glucose by splitting it into two three-carbon molecules called pyruvate -Glycolysis includes two distinct phases-energy investment and the energy generation phase -The total amount of energy produced is 8 ATPs -2 ATP(investment)+2 NADH (6 ATPs payoff ) + 4 ATP(payoff)

Answer 22

ATP is an energy transducer -Transfers energy between reactions -Not a store of energy -Produced on demand by the phosphorylation of ADP and pi

Answer 23

chemical process accompanied by or requiring the absorption of energy, the products being of greater free energy than the reactants.

Answer 24

Coenzyme has to be bound before the substrate -Coenzyme is bound tightly so that the group to be transferred is properly oriented to allow catalysis to occur -Once bound to a chemical group the structure of the coenzyme is changed , coenzymes can be considered as the second substrate of the enzymes , hence they are called co-substrates -Coenzymes need to regenerate in order to participate in the reaction again -A non protein component of an enzyme is called the cofactor -If the cofactor is organic its called a coenzyme -Coenzymes are derived from vitamins -Their role is to deliver chemical groups or atoms (hydrogen ions /phosphate)to and from the active site -The coenzyme nicotinamide adenine dinucleotide is involved in the transfer of protons -The coenzyme adenosine triphosphate (ATP)is involved in the transfer of phosphate groups

Answer 25

-Glycolysis requires the continual supply of NAD+ -Under aerobic conditions this requirement can be met by the oxidation of NADH by the ETC -Also under aerobic conditions , pyruvate can enter the mitochondria and be consumed in the tricarboxylic acid cycle (TCA) to generate even more NADH -pyruvate must leave the cytoplasm -entry of pyruvate into the mitochondria results in its complete oxidation by the reactions of the tricarboxylic acid (TCA) cycle -The outer membranes of mitochondria contains porins- proteins that allow small molecules like pyruvate to enter the intramembranous space -A pyruvate transporter (MPC) transports pyruvate across the impermeable inner mitochondrial membrane -The conversion of pyruvate to acetyl occurs in the matrix

Answer 26

-MPC faciliates the transport of the pyruvate

Answer 27

Coenzyme A-another coenzyme -CoA is an acetyl carrying group group to active sites When there is excess glucose , coenzyme A is used in the cytosol for synthesis of fatty acids

Answer 28

-Anaerobic conditions: oxygen limiting conditions -Under anaerobic conditions the cell must still generate NAD+ from NADH -One example is the conversion of pyruvate to lactate -All pyruvate has to converted to lactate under anaerobic conditions for ATP synthesis to continue

Answer 29

-Under anaerobic conditions, only 2 ATP are produced for every glucose molecule that is converted to lactate or alcohol -NADH is recycled and not used to make more ATP

Answer 30

Glycolysis:cytoplasm TCA cycle:cytoplasm ETC:Cell membrane Fermentation :cytoplasm

Answer 31

Glycolysis:cytoplasm TCA cycle:mitochondria ETC:mitochondrial membrane Fermentation:cytoplasm

Answer 32

The production of lactic acid or ethanol under anerobic conditions

Answer 33

step 1 - a carboxyl group is snipped of pyruvate and released as a molecule of CO2, leaving behind a 2 carbon molecule (acetate) step 2 - the 2 carbon moelcule is oxidised and the electrons lost are picked up by NAD+ to form NADH step 3- The oxidised 2 carbon molecule (acetyl group) is attached to coenzyme A , to form acetyl CoA

Answer 34

To carry the acetyl group to the citric acid cycle

Answer 35

-molecules of pyruvate converted into two molecules of acetyl CoA -2 carbons are released as c02 , out of the six originally present in glucose -2 NADH are generated from NAD+

Answer 36

connects glycolysis with the TCA cycle

Answer 37

in the mitochondrial matrix

Answer 38

Similarities between mitochondria and bacteria (as mitochondria believed to derive from symbiotic bacteria): -Size and shape -Both replicate by fission -Both contain circular DNA plasmids -The ribosomes that mitochondria have to make proteins are more similar to bacterial ribosomes than to eukaryotic cell ribosomes

Answer 39

-The porins in the mitochondria allow small molecules like pyruvate to enter the intermembrane space -A pyruvate transporter (MPC) transports pyruvate across the impermeable inner mitochondrial membrane -The conversion of pyruvate to acetyl occurs in the mitochondrial matrix , with the loss of 1 carbon in the form of CO2

Answer 40

in the matrix

Answer 41

Thiamine pyrophosphate

Answer 42

The reaction with TPP chemically changes the acetyl group.It is this compound that is oxidised back to acetyl while transferring to the lipoamide

Answer 43

-TPP(thiamine pyrophosphate) -Reduced lipoamide -Flavin adenine dinucleotide (FAD)

Answer 44

matrix-mitochondria

Answer 45

E1:Pyruvate dehydrogenase which uses thiamine pyrophosphate (TPP) as its prosthetic group E2:Dihydrolipoyl transacetylase which uses lipoamide and coenzyme A as its prosthetic groups E3:Dihydrolipoyl dehydrogenase which uses flavin adenine dinucleotide (FAD) and nicotinamide adenine dinucleotide (NAD+)as its cofactors Note:Prosthetic groups are molecules that are tightly bound to an enzyme or protein

Answer 46

For pyruvate dehydrogenase these include: TPP-thiamine pyrophosphate - required for pyruvate decarboxylation Lipoate-required for th transfer of the acetyl group to coenzyme A FAD-flavin adenine dinucleotide - required for the regeneration of the oxidised form of lipoate

Answer 47

-Tightly bound , non-polypeptide unit required for enzymatic activity

Answer 48

-To speed up reactions because the products of one reaction can be passed directly to the next enzyme without the newly formed substrate having to diffuse to the next enzyme

Answer 49

-3 NADH,1 FADH2 and 1 GTP(=ATP) -Relases 2 CO2

Answer 50

-4 oxidation/reduction steps

Answer 51

6 carbons -made of alpha 1,4 and alpha1,6 glycosidic bonds

Answer 52

-Branched polymer of glucose -Main chain alpha(1-4) linkage (carbon 1 joined to carbon 4) -Side chain alpha (1-6) linkage (carbon 1 joined to carbon 6)

Answer 53

Helical 12-14 glucose residues Branch occurs every 8-12 glucose 3D branching structure Up to 120,000 glucose per glycogen molecule 10-40 nm diameter

Answer 54

Glycogen granules (20-40 molecules) Up to 10% of liver mass (more as liver has to supply the whole body) 1-2% of muscle

Answer 55

catabolism=break down glycogen into glucose = glycogenolysis

Answer 56

catabolism=break down glycogen into glucose = glycogenolysis

Answer 57

Phosphoglucomutase turns 1 glucose into 6 glucose

Answer 58

Glycogen phosphorylase adds a phosphate

Answer 59

Using phosphate to break bonds = phosphorolysis

Answer 60

-Glycogen reacts with phosphate in step 1 , using the enzyme glycogen phosphorylase

Answer 61

-We use phosphorolysis to avoid wasting ATP

Answer 62

-Has a prosthetic group , pyridoxal phosphate , which is required to work

Answer 63

3 isozymes of phosphorylase(3 different versions of the enzyme)for the : -Muscle (mGP) -Brain (bGP) -Liver (lGP)

Answer 64

pyridoxal phosphate

Answer 65

PLP (pyridoxal phosphate) holds phosphate in place using hydrogen bonds

Answer 66

PLP (pyridoxal phosphate) holds phosphate in place using hydrogen bonds The enzyme binds glycogen (a polymer of glucose) and inorganic phosphate (Pi). It specifically acts on the α(1→4) glycosidic bonds at the non-reducing ends of glycogen. -We make a positively charged glucose unit -positively charged intermediate attracted to negatively charged phosphate -Processive means it doesn't let go of the substrate -Works its way along the chain = processive -Stays attached to the glycogen so doesn't need to rebind -Progression branched structure=rapid mobilization of Glycogen -Each brand tip is a source of glucose release

Answer 67

that it works its way along the chain

Answer 68

phosphoroylase cant: Break 1-6 bonds (ie it stops when it reaches a branch) Break 1-4 bonds within 4 units of branch point

Answer 69

-multiple G-1-P and limit dextrins

Answer 70

-Transferase -Debranching enzyme has transferase which moves the glucose from one part of glycogen to another part of the molecule

Answer 71

-Alpha-1,6 Glucosidase brakes the 1,6 bond which forms the side chain

Answer 72

-rearranges the molecule

Answer 73

Muscle glycogen-> glycolysis->ATP -Glycogen in muscles is broken down into glucose , which then undergoes a process called glycolysis.This is where glucose is converted into pyruvate and ATP is produced.

Answer 74

Liver glycogen->Glucogenesis>Blood glucose increases -The liver produces glucose through glucogenesis and this glucose is then released into the bloodstream , helping to raise blood glucose levels

Answer 75

-Anabolism= creating glycogen molecule=Glycogenesis

Answer 76

-Anabolism= creating glycogen molecule=Glycogenesis

Answer 77

-The phosphoglucomutase step is reversible so this stays the same , just the other way around (hence its reversible) -UDP is attached = activated form of glucose , activate molecules that we want to start sticking together -Glycogen synthase used find the tip of an existing glycogen chain and then creates a 1-4 glycosidic bond, UDP and hydrogen ion then released :

Answer 78

-UDP is attached = activated form of glucose , activate molecules that we want to start sticking together -It is now UDP-glucose

Answer 79

-Glycogen synthase used find the tip of an existing glycogen chain and then creates a 1-4 glycosidic bond, UDP and hydrogen ion then released

Answer 80

1)Glycogenin: -Builds initial 8 unit primer chain -Primer extended by Glycogen synthase

Answer 81

2)Branching enzyme: -Binds to chain 11+ units long -Cuts of heptamer of glucose units -Reattaches heptamer via a (1-6) bond -Reattachment site >4 units from existing branch

Answer 82

-Makes the chain longer

Answer 83

-Breaking down

Answer 84

-Prokaryotic cells are a lot smaller than eukaryotic cells , so prokaryotic rely on diffusion -So eukaryotic can't rely only on diffusion , hence they have this compartmentalisation

Answer 85

-Size and shape , both rod shaped -Both replicate by fission -Both contain circular DNA plasmids -The ribosomes that mitochondria have to make proteins are more similar to bacterial ribosomes than to eukaryotic cell ribosomes

Answer 86

In the presence of oxygen , the NADH can be oxidised back to NAD+ by the ETC In the presence of oxygen , pyruvate is now free to enter the TCA cycle which will be broken down to CO2 and H20 while releasing energy -The porins in the mitochondria allow small molecules like pyruvate to enter the intermembrane space -A pyruvate transporter (MPC) transports pyruvate across the impermeable inner mitochondrial membrane -The conversion of pyruvate to acetyl occurs in the mitochondrial matrix , with the loss of 1 carbon in the form of CO2

Answer 87

In anaerobic conditions , absence of oxygen , pyruvate has to be converted to either lactate or ethanol .So that the NADH cycle can be maintained in order to keep making ATP via glycolysis

Answer 88

in the matrix

Answer 89

-The oxidation of pyruvate occurs in the mitochondria of the cell .

Answer 90

Dihydrolipoyl transacetylase which uses lipoamide and coenzyme A as its prosthetic groups

Answer 91

Dihydrolipoyl dehydrogenase which uses flavin adenine dinucleotide (FAD) and nicotinamide adenine dinucleotide (NAD+)as its cofactors

Answer 92

Prosthetic groups are molecules that are tightly bound to an enzyme or protein

Answer 93

TPP-thiamine pyrophosphate - required for pyruvate decarboxylation Lipoate-required for the transfer of the acetyl group to coenzyme A FAD-flavin adenine dinucleotide - required for the regeneration of the oxidised form of lipoate

Answer 94

1-acetyl-CoA (2) and oxaloacetate (4c) combine into citrate 2-citrate (6) isomerised into isocitrate 3-Isocitrate converted into alpha-ketoglutarate ( by removing the carboxylic acid from isocitrate) , releasing C02 and generating NADH 4-Alpha-ketogultarate converted into Succinyl-CoA (4c) , releasing C02 and generating NADH 5-Succinyl-CoA makes GTP , then converted into succinate 6-Succinate makes some FADH2, loses 2 protons, and converted into Fumarate 7-Water comes in allowing another hydroxyl to be added which enables the NAD+ to be reduced into NADH and H ,Fumarate converted into Malate 8-Malate makes NADH and is then converted into oxaloacetate , to make the 6c compound again by combining oxaloacetate with acetyl-CoA to make citrate(6)

Answer 95

Citrate synthase-uses water to converted acetyl-CoA and oxaloacetate into citrate , and releases the CoA Reaction type:condensation.the first reaction is a synthase reaction , called this because a new molecule is made but ATP is not used (the latter is called a synthetase) The high free energy difference gained by the hydrolysis of this thioester to drive the reaction -Large negative value

Answer 96

-Tertiary alcohol moved from the second position to the first position, creates a secondary alcohol doing so -Isomerisation reaction catalysed by enzyme -Aconitase -Uses cofactor Fe-S complex

Answer 97

Enzyme-Isocitrate dehydrogenase reduces NAD+ into NADH , which in doing so makes the oxalosuccinate which is an intermediate reaction.The isocitrate c=dehydrogenase will then remove the carboxylic acid group to release C02 ,generating the alpha -ketoglutarate Reaction type:oxidative decarboxylation(this is the first of our 4 reduction reactions) .This is the first carbon loss as CO2, from C6 to C5 Cofactor:NAD+ is reduced to NADH + H+ Note:two step reaction , intermediate is oxalosuccinate

Answer 98

-Alpha-Ketoglutarate converted into Succinyl-CoA, using the enzyme alpha-ketoglutarate dehydrogenase -Carboxylic acid group released as C02 -NAD+ turned into NADH + H+ (this is our second reduction step)

Answer 99

Enzyme-Succinyl CoA synthetase breaks the thioester bond which allows us to generate the phosphoanhydride bond in for GTP , Coenzyme A is released -A thioester bond is a high energy bond, we can use it to generate GTP from GDP Reaction type:the energy released from the hydrolysis of the thioester bond provides the energy for the formation of the phosphoanhydride bond of GTP A substrate level phosphorylation Cofactor: GDP+Pi=GTP.The GTP can be used to form ATP (nucleoside diphosphate kinase, which is able to converted GTP into ATP) ATP and GTP are energetically equivalent ( they're the same )

Answer 100

The enzyme involves an enzyme-succinyl phosphate intermediate

Answer 101

Enzyme -Succinate dehydrogenase which reduces the NAD into NADH2, generating fumarate Reaction type:Oxidative dehydrogenation of succinate to fumarate (this is the third of our reduction reaction out of the 4 reduction reactions that occur in the TCA cycle) Cofactor:FAD is reduced to FADH2 Important note :The succinate dehydrogenase is the only enzyme contained within the inner mitochondrial membrane out of the Krebs enzymes used

Answer 102

Enzyme: Fumarase acts on fumarate to make Malate , needs water to do this , producing a hydroxyl group Reaction type:Catalyses a stereospecific trans addition of a hydrogen atom and a hydroxyl group

Answer 103

Enzyme : Malate dehydrogenase catalyses the conversion of Malate intoOxaloacetate Reaction type:Oxidative dehydrogenation of malate to oxaloacetate Cofactor:NAD+ is reduced to NADH + H+

Answer 104

-2 ATPs used to prime glycolysis -4 ATPs produced from the glycolytic pathway as a result of substrate level phosphorylation -2 NADHs generated -8 ATPs net gained from the conversion of glucose to pyruvate and the re-oxidation of the 2 NADHs produced

Answer 105

-1 NADH for the production of acetyl-CoA -3 NADHs from one turn of the TCA cycle -1 FADH2 from TCA -1 GTP directly from TCA cycle =30 ATP in total

Answer 106

-Glycolysis generates 8 ATP -TCA cycle generates 30 ATP for 2 pyruvates entering the TCA cycle Total=38 net ATPs

Answer 107

-Glucose comes in , Glycolysis occurs -Glycolysis generating the pyruvate , pyruvate has two choices -In aerobic systems its fermented which enables us to regenerate the NAD+ we need in glycolysis , completing the cycle , lactate produced -Pyruvate in our aerobic conditions enters the mitochondria , through a porin and a Mitochondrial Carrier , in the mitochondrial matrix its converted into acetyl-CoA through the link reaction and enters the TCA cycle , which generates all the reduced factors

Answer 108

-hexokinase -phosphoglucose isomerase -phosphofructokinase -aldolase -triose phosphate isomerase -GAP dehydrogenase -phosphoglycerate kinase -phosphoglycerate mutase -enolase -pyruvate kinase

Answer 109

The glycerol-phosphate shuttle and the malate-aspartate shuttle are two key mechanisms that cells use to transfer electrons from NADH produced in the cytoplasm (during processes like glycolysis) into the mitochondria, where oxidative phosphorylation occurs. This is necessary because NADH cannot directly cross the mitochondrial membrane, so these shuttles provide a means of transporting the electrons in a way that facilitates ATP production in the mitochondria.

Answer 110

-Two specific mitochondrial transporters-malate and aspartate -Results in the electrons and protons from the cytoplasm NADH being transferred to the NAD+ in the mitochondrial matrix -Any NADH made using the malate-aspartate shuttle will result in the production of 3ATP per NADH -Occurs in tissues where the energy requirements is low (such as the liver) -A different mechanism is used in metabolically active tissue such as neurons and muscle

Answer 111

Used in metabolically active tissue such as neurons and muscles -What this does is that it uses dihydroxyacetone phosphate to oxidise the NADH, producing glycerol 3-phosphate which is then used by the enzyme-mitochondrial glycerol 3-phosphate dehydrogenase and it reduces the FAD into FADH2,FADH2 is then able to donate those electrons and protons to the ubiquinone to produce the ubiquinol(in yellow) There are two glycerol-3-P dehydrogenase enzymes (cytosolic and the other mitochondrial bound with the active site on the intramembranous side) -The glycerol-3-phosphate is produced in the cytoplasm and can easily move into the intermembranous space of the mitochondria -The DHAP can pass back into the cytoplasm and be used in glycolysis -The one less ATP ensures that this reaction is not able to reverse as it decouples the matrix NADH from the cytoplasmic NADH -The oxidation / reduction cycle produced FADH2 hence using this glycerol-phosphate shuttle produces a total of 2 ATP per NADH

Answer 112

Energy balance sheet =glycerol -phosphate shuttle Glycolysis generates 6 ATP and TCA cycle generates 30 ATP for 2 pyruvates entering the TCA cycle using only the glycerol phosphate shuttle Energy balance sheet=malate-aspartate shuttle Glycolysis generates 8 ATP and the TCA cycle generates 30 ATP for 2 pyruvates entering the TCA cycle using only the malate-aspartate shuttle Total net ATP ranges from 36 (using the glycerol-phosphate shuttle) to 38 (using the malate-aspartate shuttle)

Answer 113

-within the mitochondria

Answer 114

-pyruvate comes into the intermembraneous space through a porin and then into the matrix via the mitochondrial pyruvate carrier

Answer 115

-pyruvate comes into the intermembraneous space through a porin and then into the matrix via the mitochondrial pyruvate carrier

Answer 116

specific transporters

Answer 117

-Porins allow the NADH access to the intermitochondrial space for small molecules

Answer 118

-FADH2 is made on the inner membrane and its made by the succinate dehydrogenase enzyme which is the enzyme that turns the succinate into fumarate -The succinate dehydrogenase sits in the inner membrane and is also a component of the electron transport chain

Answer 119

Succinate dehydrogenase= 4 subunit protein, protein complex , large region stretches out into the matrix

Answer 120

-NADH and FADH2 pass their electrons to transmembrane protein complexes within their inner membrane -At each step the electrons are passed to the next carrier in the chain - that carrier has a slightly higher affinity for electrons than the previous carrier -Ultimately , the electrons are passed to molecular oxygen to produce water

Answer 121

5 complex 1 , complex 2 ,complex3,complex4,complex 5

Answer 122

1,3,4 are proton pumps , they transport H from the matrix into intramembranous space

Answer 123

-consist of 2 gates , gate 1 opens on matrix side , proton comes in and binds to negatively charged AA as they're positively charged and it will associate tightly with them -Close the gate -Open the intramembranous space gate (the bottom one) -need to dissociate proton,as the electrons travel through the protein complex they provide energy and this energy is used to dissociate the protons from the protein complex to position them into the intramembranous space

Answer 124

-Also known as NADH ubiquinone reductase / NADH-Q reductase -Oxidises NADH and transfers 2 electrons through protein structure(the mobile carrier ubiquinone) , it provides the energy thats needed to pump 4 protons from matrix side into intramembranous space, these electrons and protons combine with ubiquinol to produce reduced ubiquinone -Reduced ubiquinone called ubiquinol (QH2) is free to move throughout the inner membrane -Ubiquinol transfers these electrons to complex 3 -The transfer one of the electrons through complex 1 will result in two protons from the matrix into the intermembraneous space

Answer 125

-Called Q-cytochrome-c oxidoreductase -Transfers two electrons between two mobile electron carrier -It receives them from the QH2 (ubiquinol) and transfers them to the soluble cytochrome-c located in the intramembranous space -1 electron is transferred to 1 cytochrome-c (an electron acceptor)with the transfer of approximately 2H+.The second electron is first stored internally and then transferred to a second cytochrome c which results in two additional H+ being transferred from matrix to intramembranous space -There are a total of 4H+ transferred ,2 from QH2 and 2 from the matrix -cytochrome carries electron so we need two of these (have two cytochrome-c)

Answer 126

-Also called cytochrome oxidase -This transfers the 2 electrons from the 2 cytochrome-c proteins to the mitochondrial matrix -This is accompanied by the transfer of 2H+ to the intramembranous space and reducing oxygen on the matrix side to produce water -Hence the oxidation of one NADH results in the transfer of approximately 10 H+ (4 from complex 1 , 4 from complex 3 and 2 from complex 4) to the intermembraneous space

Answer 127

-It is complex 2 that in the conversion of succinate to fumarate , FAD is reduced to FADH2

Answer 128

-ATP synthase -Protons from from intermembraneous space through the protein , and the rotor rotates quickly , generating ATP quickly -If the ATP synthase has stopped using the protons then at some point the proton gradient will be so high that the proton transfer stops

Answer 129

-Beta subunits can be in three forms : open state , lose state and tight state

Answer 130

-ADP and Pi binds to open state of Beta subunit , gamma subunit rotates and as this rotates it turns into the loose confirmation , the gamma subunit rotates again and forms the closed complex , which forces the ADP and Pi together to produce ATP -the return of the H+s causes rotation of the spindle of the ATP synthase (rotor) -The rotor is asymmetric and causes conformational changes in the head group subunits that make up the stator -These conformational changes in the stator ( the stationary part fo the enzyme complex) are involved in the driving the synthesis of ATP from ADP and Pi -It is not the synthesis of ATP but the unbinding that requires energy

Answer 131

-We have this transporter , ATP-ADP translocase in the inner mitochondrial membrane which recognises ADP and ATP and swaps the places of them -It is the voltage gradient that drives ATP/ADP movements as -4 charge on ATP prefers to move out while -3ADP moves into the matrix

Answer 132

-ADP level rises -ADP enters the matrix and ATP leaves -ADP can now be phosphorylated by the ATP synthase using the proton motive force -The proton motive force is reduced -The electron transport chain starts up again to rent the proton motive force -Hence ATP is only produced on demand

Answer 133

hydrophobic

Answer 134

triglycerides

Answer 135

fat=solid at RT oil=liquid at RT

Answer 136

3 fatty acids are ester-linked to glycerol backbone

Answer 137

-long chain (between 12 and 24 carbons ) hydrocarbons -Methyl group at one end , COOH (carboxyl ) group at one end -0 or more double bonds (none at all or several ) -no double bonds = saturated=higher melting point -unsaturated = several double bonds= lower melting point

Answer 138

Polyunsaturated = more than 1 double bond monounsaturated= one double bond -The double bonds change the properties -More double bonds you turn fats into oils (lower melting temp)

Answer 139

cis= same side , has a kink in it , cant pack as closely together , lowers the MP Poly-cis = bend becomes more curled Trans = opposite side (across) , linear

Answer 140

-common name EG-Oleic acid -Systematic name - cis octadecenoic acid -omega or n system - C18:1 (n-9) -omega is the position of the first double bond

Answer 141

Elongases -increase chain length by 2 carbons Desaturases-add double bonds We cant make fatty acids less than omega 9

Answer 142

-Humans don't have the right desaturase to add double bonds lower than omega 9 -Omega 3 / omega 6 fatty acids therefore have to come from the diet and are termed essential -Omega 3 + omega 6 can be elongated and further desaturated

Answer 143

-no need for energy storage purposes -membrane phospholipids Fatty acid length increases bilayer thickness Degree of saturation increases membrane fluidity Tissue-specific membrane composition Some fatty acids are precursors to signalling molecules

Answer 144

triglycerides digested by pancreatic lipases

Answer 145

-majority of lipid in food is triglycerides -digested by pancreatic lipases -water come in and split the ester bond , water added -Triglycerides are too big to be absorbed as they are , so this is why this occurs -can now cross membrane into intestinal cells

Answer 146

-digested triglycerides are re-esterified in gut mucosa -Fatty acids have to be activated first using Coenzyme A -Triglycerides are packaged into lipoproteins for transport in the blood to the tissues as they are too hydrophobic otherwise

Answer 147

-Triglycerides are packaged into lipoproteins for transport in the blood to the tissues as they are too hydrophobic otherwise

Answer 148

Lipoprotein -mixture of lipid and protein -phospholipid and chlol (OH group )outer layer -tylerglericde and chol ester core -transport from gut to tissues uses chylomicrons

Answer 149

Lipoprotein -mixture of lipid and protein -phospholipid and chlol (OH group )outer layer -tylerglericde and chol ester core -transport from gut to tissues uses chylomicrons

Answer 150

-Endothelial cells have Lipoprotein lipase attached on the lumenal side -endothelial cells coated with an enzyme -lipoprotein lipase cleaves off fatty acids when enter cells -When chylomicron has offloaded most of the TG it is called a remnant and is removed from circulation by the liver -all three fatty acids cut off -chylomicron offloads the triglycerides

Answer 151

White adipose tissue (WAT) White adipose tissue = storage -Tg synthesis here is different from intestinal synthesis -all 3 FA need to be activated again -Glycerol-3-phosphate comes from DHAP (glycolysis) Use NAD+ to add on a hydrogen

Answer 152

-triglycerides come in , in the food -In the gut they are broken down into 2 fatty acids and 1 monoacylglycerol -in the gut lining they are turned back into a triglyceride -then loaded onto lipoproteins to travel around the body -Then broken down again into 3 fatty acids and glycerol -then turned again back into triglycerides

Answer 153

-They contain lots of energy , more than glucose (glucose = 17 , fatty acids= 38 ) -Makes a better source than glucose as when glucose stored as glycogen , there is a high mass of water -They form a dense energy store -Fatty acids form a pure droplet of triglycerides so not wasting space with water

Answer 154

-Specialised for storing triglycerides -Each fatty acid droplet has a shell of protein around it -Protein shuts off the droplet

Answer 155

-The three enzymes used in lipolysis are : Adipose triglyceride lipase (ATGL), hormone-sensitive lipase (HSL) and Monoacylglycerol ( MGL) -Coat is open after phosphorylation -Set of 3 enzymes -Each enzyme is recognised and cleaves a different fatty acid

Answer 156

-The three enzymes used in lipolysis are : Adipose triglyceride lipase (ATGL), hormone-sensitive lipase (HSL) and Monoacylglycerol ( MGL) -ATGL is the enzyme that is responsible for the initial step in lipolysis , it cleaves the fatty acid from the triglyceride , converting it into a diacylglycerol (DAG) and free fatty acid (FFA) -After ATGL acts on the triglyceride , HSL further breaks down the diacylglycerol (DAG) , it cleaves the second fatty acid , resulting in a monoacylglycerol (MAG) and another free fatty acid -The first step of lipolysis involves MGL (monoacylglycerol ) which cleaves the remaining FA from the MAG producing glycerol and a free fatty acid -Coat is open after phosphorylation -Set of 3 enzymes -Each enzyme is recognised and cleaves a different fatty acid

Answer 157

The breakdown is only in adipose tissue so needs to be transported in the blood to somewhere else -HSA carries the fatty acids in the blood -Delivered to areas of the body with low conc

Answer 158

-HSA carriers the FA into the blood -delivered to areas of the body with low conc -target within the cell is the outer membrane of the mitochondria -FA are released from HSA and travel to the outer membrane of a mitochondrion where theyre activated

Answer 159

-When they reach the surface they attach to coenzyme A , to make Acyl CoA -This consumes ATP which is catalysed by an enzyme called Acyl CoA synthetase -Synthetase means it consumes ATP -No energy cost for the next step -2 step process -Carboxylic group reacts with ATP , we attach AMP to the end , releasing pyrophosphate (pp)

Answer 160

-CoA must be swapped for carnitine to cross the inner mitochondrial membrane

Answer 161

-Acyl-carnitine is transported across the bilayer by a Translocase antiporter

Answer 162

-Acyl-CoA can cross the outer mitochondrial membrane -CoA must be swapped for carnitine to cross the inner mitochondrial membrane -Acyl-carnitine is transported across the bilayer by a Translocase antiporter -Acyl chain is reattached to CoA once in the matrix -Need to get across 2 membranes in the mitochondria the inner and outer membrane -Fatty acids comes in and binds to protein acyl-CoA synthetase then goes through the membrane -Goes from being attached to CoA to being attached to carnitine -Carnitine swaps with the carintine attached to the fatty acid -Allows two separate pools of fatty acids , one in the cytoplasm and one in the mitochondria

Answer 163

acyl CoA - can chop off 2 carbons at a time from the acyl CoA ( 2 carbons removed from Acyl CoA then becomes the acetyl CoA) to feed it into the TCA cycle -Acetyl CoA is a mini fatty acid that can be made from a full sized fatty acid

Answer 164

-Breaking the bond will release Acetyl CoA -Going from an attacked fatty acid to acetyl CoA= Beta oxidation -Only 2C are ever removed at one time -Bond in pink is the one that is broken which releases an acetyl CoA Products = Acetyl CoA which goes into the TCA cycle and Acyl CoA which goes into round 2 of beta oxidation Four step process to release each 2C from FA (page 74 )

Answer 165

Step 1 - removed hydrogen from beta and alpha to make C-C double bond , FAD picks up the hydrogens , breaks a double bond , get 2 ATPs out -Oxidation of alpha and beta carbons

Answer 166

-Can use water to add oxygen to the H to create an OH group and then 2 more H to create a single bond between the carbon -Creates a carbonyl group on the beta carbon -(step 3)Two hydrogens removed , by the dehydrogenase, one goes to NADH , the other goes to the ETC -No energy has been consumed yet

Answer 167

-each cycle produces -1 acetyl CoA -1 FADH2 -1 NADH

Answer 168

-The number of cycles needed = number of carbons / 2 - 1

Answer 169

Excess amino acids arent stored Excess of aa arent excreted , not lost in urine , because there is energy in them and theyre useful molecules

Answer 170

Aa have nitrogen atoms within them , there is an aa pool in the body , this is the free aa in the blood so cells can take the ones they need 250 new body protein made a day , aa leave the aa pool and make body protein Constantly recycling proteins in the body Same amount each day broken down or turned into something

Answer 171

1-Protein synthesis 2-Direct use / minor modification 3-Breakdown and redeployment

Answer 172

AA used to make neurotransmitters Direct use: Neurotransmitters Glutamate , Aspartate and Glycine Glutamate used to make GABA Tyrosine - Dopamine , Noradrenaline , Adrenaline Tryptophan used to make Serotonin Arginine used to make NO Hormone Tyrosine-Thyroxine Tryptophan - Melatonin

Answer 173

-amino group chopped off , problem is its ammonia which is toxic to cells , so is a partial solution -a carbon skeleton is left(lost amino group) - can be turned into c02 and water , by breaking down carbon skeleton , to produce ATP -carbon skeleton can be the starting point to make other useful molecules in the body

Answer 174

-need to detoxify the amino -amino group is therefore stuck on alpha ketoglutarate and made into glutamate -no energy cost -Deamination is the removal of the amino group , into ammonia -ammonia converted to urea , easier to get rid of now -this is a funnelling effect -the carbon skeleton can go round again for another amino group to attach to , cycle will continue -page 91

Answer 175

Transamination- an amino acid from one amino acid is transferred to a keto acid ( alpha-ketoglutarate) to form a new amino acid

Answer 176

-family of enzymes called aminotransferase -swap oxygen for NH2 -alanine gets converted into pyruvate -turn aa into something that can or is already into the TCA cycle -This is the livers job to do this process -use water to break double bond , release ketoacid -alphaketoglutuarte comes in -reverse this process -water released -rearrangement of double bond -amino group now on a different carbon skeleton -no energy cost to do this page 92

Answer 177

Deamination-process of removing the amino group from an amino acid

Answer 178

-glutamate reacts with water hydrolysis reaction , releases ammonia -glutamate dehydrogenase catalysis this producing NADH,generating ATP -enzyme highly regulated , inhibited by GTP,activated by ADP

Answer 179

-c02 , ammonium , ATP and water react -Produce carbamoyl phosphate-Cycle of AA different to ones found in protein apart from arginine Citrulline reacts with aspartate to produce arginino succinate -this is split into arginine and fumarate -arginine is hydrolysed to release urea and regenerate into ornithine

Answer 180

-catabolise aa to ammonia but cant make urea

Answer 181

Carbon skeletons all end up as one of : Pyruvate Acetyl CoA Acetoacetyl CoA Alpha Ketoglutarate Succinyl CoA Fumarate Oxaloacetate

Answer 182

Overview of fatty acid anabolism -starting point is Acetyl CoA (2c) -endpoint if Palmitic acid (16c) -process is almost a reverse of beta oxidation (beta carbon being reduced) (due to the use of NADPH rather than NADH and the use of Malonyl CoA as a basic unit - not Acetyl CoA)

Answer 183

Synthesis of fatty acids through fatty acid biosynthesis Step 1 Carboxylation of Acetyl-CoA to Malonyl-CoA: -start with acetyl CoA , ATP and HCO3 react with each other first, Acetyl coA carboxylase is adding a carboxy to something -The enzyme is highly regulated, stimulated by the presence of citrate in the cell ,insulin stimulates this pathway , the palmitic acid is a negative inhibitor (negative feedback loop), Glucagon and adrenaline inhibit Acetyl CoA carboxylase

Answer 184

Step 2:Fatty acid synthesis elongation -Chain grows by 2c at a time -Acetyl-CoA and malonyl-CoA are transferred to fatty acid synthase (FAS) -one of the carbons is released as carbon dioxide, release of CO2 drives the reaction -make a 4 carbon molecule

Answer 185

-both in the cytoplasm

Answer 186

-Both FAS and Acetyl CoA carboxylase are in the cytoplasm -All acetyl CoA are in the mitochondria -We need to have some shuttles -Starting point is a build up of Acetyl CoA , reacts with citrate , we then have a transporter for citrate which moves citrate into the cytoplasm -citrate is converted back to Acetyl CoA and back to oxaloacetate

Answer 187

-The first step of fatty acid synthesis involves the binding of acetyl-CoA to the acyl carrier protein (ACP) domain of fatty acid synthase -Acetyl-CoA then reacts with the sulfhydrl group of ACP , creating the acetyl-ACP complex -FAS is a huge enzyme , with 6 different active sites -The bold part is not a polypeptide , but the rest is -page 83

Answer 188

-step 1 is the first two domains, forms the bond and joins them together, making C-C bond is step 1 a)Acetyl group transferred to KS via ACP and MAT KS= beta ketoacyl-ACP synthase MAT=Malonyl/Acetyl CoA-ACP Transacylase b) Malonyl transferred onto ACP by MAT c)KS joins the Acetyl and Malonyl (loss of co2) Step 2 , 3 and 4 we need to get to a CH2 group Step 2 - carbonyl to CHOH, reduction gets rid of carbonyl Step3-single carbon bond to double carbon bond , dehydration gets rid of oxygen Step 4-Adds hydrogen to CH to make CH2, reduction makes it into CH2, the goal is to use NADPH to remove the oxygen and add 2 hydrogens

Answer 189

-the 4c chain is transferred back to KS to start off step 1 -teh cycle is repeated 6x until enough 2c have been added to make palmitic acid (16c) which is then released (thioesterase) -Cycle continues until enough carbonyl are added -Ends up on flexible arm but needs to be cut off to make it a free FA which can then be attached to glycerol to form a triglyceride

Answer 190

-In anabolic state , new FA will be converted to TG and stored -If synthesised in the liver , lipoproteins used to export TG to adipose and other tissues

Answer 191

phospholipids,cholesterol,triglyceride,cholesteryl ester

Answer 192

VLDL- very low density lipoprotein IDL-intermediate denisty lipoprotein LDL-low density lipoprotein HDL-high density lipoprotein -5 types of chylomicrons -Theres a density gradient -As they get smaller they get more dense

Answer 193

Excess amino acids arent stored Excess of aa arent excreted , not lost in urine , because there is energy in them and theyre useful molecules

Answer 194

Aa have nitrogen atoms within them , there is an aa pool in the body , this is the free aa in the blood so cells can take the ones they need 250 new body protein made a day , aa leave the aa pool and make body protein Constantly recycling proteins in the body Same amount each day broken down or turned into something

Answer 195

1-Protein synthesis 2-Direct use / minor modification 3-Breakdown and redeployment

Answer 196

AA used to make neurotransmitters Direct use: Neurotransmitters Glutamate , Aspartate and Glycine Glutamate used to make GABA Tyrosine - Dopamine , Noradrenaline , Adrenaline Tryptophan used to make Serotonin Arginine used to make NO Hormone Tyrosine-Thyroxine Tryptophan - Melatonin

Answer 197

-amino group chopped off , problem is its ammonia which is toxic to cells , so is a partial solution -a carbon skeleton is left(lost amino group) - can be turned into c02 and water , by breaking down carbon skeleton , to produce ATP -carbon skeleton can be the starting point to make other useful molecules in the body

Answer 198

-need to detoxify the amino -amino group is therefore stuck on alpha ketoglutarate and made into glutamate -no energy cost -Deamination is the removal of the amino group , into ammonia -ammonia converted to urea , easier to get rid of now -this is a funnelling effect -the carbon skeleton can go round again for another amino group to attach to , cycle will continue Transamination- an amino acid from one amino acid is transferred to a keto acid ( alpha-ketoglutarate) to form a new amino acid

Answer 199

an amino group from one amino acid is transferred to a keto acid ( alpha-ketoglutarate) to form a new amino acid

Answer 200

-family of enzymes called aminotransferase , they transfer amino groups from one thing to another -swap oxygen for NH2 , becoming glutamate -Swapping carbonyl for an amino , becoming an alpha keto acid -bidirectional

Answer 201

Aminotransferases use a Vit B6-derived prosthetic group called pyridoxal phosphate (PLP) to do the amino group transfer Picture on P92: -use water to break double bond , release ketoacid -alphaketoglutuarte comes in -reverse this process -water released -rearrangement of double bond -amino group now on a different carbon skeleton -no energy cost to do this

Answer 202

Deamination-process of removing the amino group from an amino acid

Answer 203

-glutamate reacts with water hydrolysis reaction , releases ammonia -glutamate dehydrogenase catalysis this producing NADH,generating ATP -enzyme highly regulated , inhibited by GTP,activated by ADP

Answer 204

-all AA -Cycle of AA different to ones found in protein apart from arginine Citrulline reacts with aspartate to produce arginino succinate -this is split into arginine and fumarate -arginine is hydrolysed to release urea and regenerate into ornithine

Answer 205

Extrahepatic tissues refers to all the tissues and organs in the body outside the liver

Answer 206

ammonia (NH3)

Answer 207

Pyruvate Acetyl CoA Acetoacetyl CoA Alpha Ketoglutarate Succinyl CoA Fumarate Oxaloacetate

Answer 208

-page 96 -M converted to SAM -SAM changed into S -Then changed into homocysteine -VitB6 , reaction with serine produces cystathionine -Overall product is succinyl CoA

Answer 209

by combining carbon skeletons from three AA

Answer 210

Gluconeogenesis= new glucose creation , make glucose

Answer 211

-Three in pink cant be reversed -Need alternative routes , pyruvate to oxaloacetate to EP , 2 ATP consumed -get rid of phosphate on fructose 1-6 bisphosphate , hydrolyse the bond back into fructose 6 phosphate -chop of phosphate from glucose 6 phosphate into glucose -all other arrow can run in either direction -lower part has to run twice -6 ATP used Pyruvate cant go back to PEP Need an alternative pathway -pyruvate carboxylase - movies round carboxyl groups -add co2 onto pyruvate to make oxaloacetate -This is in the mitochondria -Either the malate or aspartate shuttle transfers OAA to cytoplasm PEPCK- moves carboxyl group -CO2 added on -simple hydrolysis -fructose 1-6 bisphosphate hydrolysed into fructose 6 phosphate -glucose 6 phosphate hydrolysed into glucose -Glucose 6 phosphate cant cross the plasma membrane , so only when converted to glucose it can cross the membrane

Answer 212

lactate via the cori cycle and glucogenic amino acids

Answer 213

Need an alternative pathway -pyruvate carboxylase - movies round carboxyl groups -add co2 onto pyruvate to make oxaloacetate -This is in the mitochondria -Either the malate or aspartate shuttle transfers OAA to cytoplasm

Answer 214

-conversion of lactate -uses LDH - lactate dehydrogenase -Lactate travels through the body to the liver, the liver turns the lactate into pyruvate and then joins 2 pyruvates together to make glucose

Answer 215

Glucogenic AA- means AA that can be used in gluconeogenesis

Answer 216

-muscle proteins are broken down into AA -muscles undergo transamination , a process where amino groups are transferred from AA to form glutumate and pyruvate , allowing for the release of alanine -in the liver , alanine is converted back into pyruvate via the action of the enzyme alanine aminotransferase (ALT) -the amino group of alanine is transferred to alpha-ketoglutarate which forms glutamate -pyruvate formed in the liver is then used in gluconeogensis to synthesize glucose -10 ATPs everytime we do this -Only the liver does this

Answer 217

-glycerol phosphoroylated by glycerol kinase to form glycerol-3-phosphate , consumes 1 ATP -glycerol-3-phosphate oxidised by glycerol-3-phosphate dehydrogenase to form dihdryoacetone phosphate, produces 1 NADH -1 ATP consumed , 1 NADH created

Answer 218

-the enzymatic route that a metabolite molecule takes

Answer 219

1-measure Vmax for enzymes in pathway , lowets = RLS 2-compare Keq and mass action (MAR) -If reaction is close to equilibrium in the cell MAR=Keq -If reaction is rate-limiting in the cell MAR

Answer 220

1-measure Vmax for enzymes in pathway , lowets = RLS 2-compare Keq and mass action (MAR) 3-Test if at crossover point (-To see whether its an enzyme that changes activity when u change the conditions -stimulation may be enzyme -before enzyme D substrate levels drop and after product levels increases -D slows down the whole pathway)

Answer 221

To ensure a given metabolic pathway is active when its product is needed Ensure competing pathways arent simultaneously active ie dont want to make and break down glycogen at same time Ensure co-ordinated activity in multiple related pathways , ensuring the right things are on and off at the right time

Answer 222

-we dont want futile cycling , it wastes ATP -Waste energy comes off as heat Brown adipocytes deliberately use futile cycling

Answer 223

Intrinsic control by metabolites : allosterism / inhibitors Fast extrinsic control via hormones (not influenced by whats going on inside the cell ): covalent modification -EG-phosphorylation Slow extrinsic control via hormones : gene expression

Answer 224

-A=product inhibition: -hexokinase joins a phosphate to glucose = glucose 6 phosphate -These then go back into the active site and prevent any further production -a product can inhibit its own production -B=Allosterism -example for fructose e,6-bisphosphate -phosphofructokinase adds a phosphate to a different place -This then stimulates the PDK-1 enzyme to break down the build up of F-6-P faster -ADP and ATP are also going to have a feedback effect –citrate building up is a signal you have plenty pf ATP , inhibiting glycolysis , stimulating gluconeogenesis -If you have lots of ATP you dont need to to glycolysis , ATP inhibits the PFK-1 enzyme -AMP levels should never build up in the cell , if it does its a signal the cell is starving -The liver should not release glucose therefore , it should be doing glycolysis and stimulates the PFK-1 enzyme -PFK-2 is inhibited by citrate and PEP but not ATP , activated by Pi -page 113 -ATP will inhibit the pyruvate kinase step -ADP inhibits both of the steps on the left (negative sign) -Acetyl CoA build up stimulates gluceogenic pathway -Alanine inhibits pyruvate kinase -Alamine suggest we are breaking down the muscle due to short glucose -Glycolysis is heavily regulated

Answer 225

-PFK1 -Pyruvate kinase -Pyruvate dehydrogenase -Citrate synthase -Isocitrate dehydrogenase -Alpha ketogluturate dehydrogenase -All of these enzymes are inhibited by ATP -Lots of ATP means we dont need to do the metabolic pathway -ADP/AMP activate and stimulate the enzymes in the pathway

Answer 226

hormones can alter : the actvitity of enzymes (rapid , via phosphorylation , short lived effect) and number of enzymes (slow , via gene expression changes, longer-lived effect) -Hormones can change the number of enzyme molecules present as well as the activity of the enzymes

Answer 227

phosphorylation=conformational change = activation / inactivation = phosphorylation ovverides allosterism -3 amino acid side chains that contain a phosphate -Kinase adds a phosphate , phosphatase removes a phosphate , this causes a conformational change -This is a permanent change that overrides the allosteric step

Answer 228

-metabolites -phosphorylation

Answer 229

inactive form phosphorylase B and an active form phosphorylase A

Answer 230

-In the muscles its stimulated by AMP , inhibited by ATP and G-6-P -In the liver its inhibited by glucose -In both cases (both B and A ) serine 14 can be phosphorylated it can then become active

Answer 231

-muscle = 9 liver = 7 -six different kinases = inhibtion -Glycogen synthase has lots of phosphorylation sites , activating and stimulating the breakdown of glycogen and inhibits the synthesis of glycogen -6 different kinases that all add a phosphate to glycogen synthase , all inhibit it

Answer 232

-Both adrenaline and glucagon will bind to a receptor and activate a G protein -The G protein will cause the production of cyclic AMP -cyclic AMP then activates a protein kinase -This activated protein kinase then phosphorylates other enzymes -Phosphorylase kinase is activated , this attaches a phosphate onto phosphorylase making it active , this is the one that breaks down the glycogen -add a phosphate to glycogen synthase its inactive -add a phosphate to phosphorylase alpha = activated -page 117

Answer 233

-Insulin promotes dephosphorylation

Answer 234

-Insulin promotes dephosphorylation -the hormone lipase(hormone sensitive lipase ) isnt very active when its dephosphorylated -perpilipin is in the way of the triglycerides

Answer 235

-On the other side (right side ) we see everything is the opposite , when high levels of adrenaline everything becomes phosphorylated so now the perilipin move out of the way and allow access to the triglycerides and the hormone sensitive lipase is now fully active and starts breaking them down , FA released from this store

Answer 236

In its dephosphorylated state, fructose-6-phosphate (F-6-P) is converted into fructose-2,6-bisphosphate (F-2,6-P2) by the enzyme PFK-2. This activates PFK-1, stimulating glycolysis.

Answer 237

When adrenaline is dominant, it causes PFK-2 to become phosphorylated. This phosphorylation inactivates PFK-2's kinase activity, leading to a decrease in fructose-2,6-bisphosphate (F-2,6-P2) levels. As a result, the FBPase2 activity (which is the phosphatase function of PFK-2) becomes more prominent, favoring gluconeogenesis and inhibiting glycolysis.

Answer 238

Insulin promotes the dephosphorylation of PFK-2. When PFK-2 is dephosphorylated, its kinase activity is enhanced, leading to an increase in fructose-2,6-bisphosphate (F-2,6-P2) levels. This increase in F-2,6-P2 activates PFK-1, which stimulates glycolysis

Answer 239

Inhibitors: ATP, NADH, and Acetyl CoA inhibit the link reaction. Stimulator: ADP stimulates the link reaction.

Answer 240

In the dephosphorylated state, PDH is active, meaning it can convert pyruvate to acetyl-CoA. In the phosphorylated state, PDH is inactive, and it cannot perform this conversion

Answer 241

PDH phosphatase removes the phosphate groups from the PDH complex, reactivating the enzyme. -PDH kinase adds a phosphate , inactivating the complex so that pyruvate can no longer convert into Scetyl CoA -ATP,NADH,Acetyl CoA will inhibit it (conversion of pyruvate to Acetyl CoA) -ADP will stimulate it -In the dephosphorylate state its active , in the phosphorylated state its not active -PDH kinase (pyruvate dehydrogenase kinase ) switches it off -PDH phosphatase switches it back on again -The phosphorylation can also be controlled allosterically , ATP , NADH , Acetyl CoA stimulate the PDH Kinase -CoA , ADP and NAD+ inhibit the PDH Kinase -Pryuvate will also inhibits the PDH Kinase -Calcium ions inhibit the PDH Kinase but stimulate the PDH phosphatase -Dont need to learn every arrow in this diagram

Answer 242

Links allosterism to phosphorylation Energy sensor AMP binds cooperatively and allosterically -> 1000-fold increase in activity of AMPK Phosphorylates multiple targets (enzymes and transcription factors) Activated by Metformin (diabetes drug)

Answer 243

-trancsription factors bind genes and eother increase / decrease expression -TF either activate / deactivate a gene -Conc of enzymes in cell goes up or down , Vmax goes up or down , rate goes up or down -Two explanations : some TFs are metabolite receptors , gene binding follows the binding on the metabolite -Phosphorylation of Tfs , causes gene binding

Answer 244

-CREB=cyclic AMP responsive element binding protein

Answer 245

CREB (cyclic AMP responsive element binding protein) is a transcription factor that regulates gene expression. It is activated by phosphorylation and can bind to the CREB binding element (a specific DNA sequence) to initiate transcription.

Answer 246

When CREB is dephosphorylated, it is inactive and cannot bind to the CREB binding element, thus not promoting transcription.

Answer 247

CREB is activated when protein kinase A (PKA) phosphorylates it. Once phosphorylated, CREB can bind to the CREB binding element, a specific stretch of DNA, to initiate transcription. -CREB is inactive when its dephosphorylated , PKA then phosphorolyates it and can now bind to a region called the CREB binding element ,a binding element is a stretch of DNA that a transcription factor can bind too -We have the same hormone but two different effects : phosphorylation and transcriptional regulation

Answer 248

-Lipoprotein lipase cleaves off fatty acids , which enter cells -Someone who exercises lots has lots of lipoprotein lipase , so the chylomicron can offload more FA -By doing exercise we have lots of lipoprotein lipase on the cell , so more fatty acids are removed from chylomicron onto the lipoprotein lipase

Answer 249

Allosterism /inhibitors : very quick , graded but limited effect Phosphorylation : quite quick , on/off effect Gene expression : Slow but sustained effect Vmax can increase /decrease, mutations in the gene knock Vmax into 0

Answer 250

Intrinsic control by metabolites : allosterism / inhibitors Fast extrinsic control via hormones : covalent modification Slow extrinsic control via hormones : gene expression Mixtures of 1-3

Answer 251

Dietary additions : Caffeine , its a purine , similar to adenine and guanine , it can sometimes take place of these molecules but doesnt do the function of the molecules , ie its an inhibitor , inhibitor of cAMP phosphodiesterase -caffiene inhibits cAMP phosphodiesterase = more protein Kinase A -cAMP phosphodiesterase switches of everything that Cyclic AMP stimulates -cAMP phosphodiesterase breaks down the cyclic AMP , meaning it no longer activates protein Kinase A and you therefore dont get the rest of the cascade -Caffeine inhibits the cAMP phosphodiesterase= more protein Kinase A -Overall effect = more protein Kinase A in the cell -caffeine also influences gene expression -Boosting glycogenolysis and lipolysis , releasing energy molecules into the body for use

Answer 252

Fed state High fructose Alcoholism Fasting state Starvation Exercise Thermogenesis Insulin resistance / diabetes

Answer 253

-fatty acids and glycerol

Answer 254

Heart:preferred fuel are ketone bodies (heart runs on ketone bodies)

Answer 255

Intestines: preferred fuel source is glutamine

Answer 256

Immune cells : preferred fuel source is glutamine Spermatozoa : only fuel source is fructose

Answer 257

-Blood glucose levels go up or rise in leucine = release insulin

Answer 258

-Blood glucose levels drop or the levels of glucogenic AA increases = release of glucagon

Answer 259

-50% of this glucose used in glycolysis , 10% used to convert into glycogen 30% used in triglycerides -AA used to make proteins and some diverted into carbon skeletons -FA used in triglycerides

Answer 260

-FA absorbed by gut and go into Adipose tissue into TG -FA taken up by muscle and turned into TG Glucose taken up by liver turned into glycogen -Glucose taken up by muscle , converted into glycogen in muscle -The liver turns excess glucose into TG , same happens in adipose tissue -AA turned into protein in muscles -Liver turns AA into some sort of carbon skeleton if in excess

Answer 261

-Glycogen synthase switches on , phosphorylase switched off -Pyruvate kinase turned on (more active) -In the anabolic state theres a boost of glycogen synthase (due to increase in glycogenesis ), because we are trying to make glycogen and at the same time we switch of phosphorylase (decrease in glycogenolysis) -We boost glycolysis , so pyruvate kinase boosted -We cancel gluconeogenesis because at this stage we have lots of glucose , dont need to make it

Answer 262

-Boost in Acetyl CoA carboxylase , this is used to make malonile CoA - the starting point for making FA

Answer 263

-boost in activity of pyruvate dehydrogenase ,makes more acetyl CoA to make more FA

Answer 264

-big inhibition of Hormone sensitive lipase , big drop in breakdown of triglycerides -Tiny amount of insulin to stop the breakdown of fats

Answer 265

-Glucokinase levels are boosted - speeds up glycolysis -Drop in the levels of gluconeogenesis enzymes -in terms of glucose , theres a boost of glycolysis in adipose tissue

Answer 266

-Malic enzyme + ATP citrate lyase used for boosting FA synthesis Adipose tissue : (bottom half of diagram) in terms of glucose -Have a boost of glycolysis , to make Acetyl CoA to make FA but also to make glycerol

Answer 267

-Have a boost of glycolysis , to make Acetyl CoA to make FA but also to make glycerol

Answer 268

-In terms of triglycerides theres a boost of lipoprotein lipase (boost in FA entry) -boost in the enzyme glycerol3-P acyltransferase (as we need a source of glycerol)-boost in lipogensis

Answer 269

glucose transporter

Answer 270

-Most tissues in the body will have GLUT 1 + 3 = have a low Km , high affinity transporters for glucose and Hexokinase 1-3 , low Km , high affinity

Answer 271

-Liver has GLUT 2 which is a lower affinity transporter-high Km -Liver has HK IV (its hexokinase 4 also known as glucokinase) - High Km - low affinity , not inhibited by G-6-P

Answer 272

-Muscle and adipose tissue (these are the two insulin responsive tissues )contain GLUT-4 , not present on membrane , medium Km , GLUT4 is inside the cell (induced by insulin ) -Muscle and adipose tissue contains HK (hexokinase ) 2 - low Km

Answer 273

-Insulin turns glucose into fat = more fat made -Insulin blocks fat breakdown thats already in adipose tissue = no fat used -One way process of these cause the fat stores to swell

Answer 274

Derangement of metabolism : fructose High fructose corn syrup (HFCS) Sweetener in food Less glucose than sugar Less insulin release Less fat storage But: fructose is metabolised faster than glucose in the liver

Answer 275

-In the liver it has its own fructokinase -Product split into DHA and glyceraldehyde -Have triose kinase that sticks the phosphate onto the products -We are short circuiting glycolysis here , skipped the two steps that are slowed down -This runs faster than when we start with glucose -Avoiding the regulating steps and is quicker process -Fructose ends up as FA

Answer 276

-Ethanol turned into Acetyl CoA -Alcohol dehydrogenase is the first step and this generates NADH , this produces Acetaldehyde - This then gets turned into Acetate by aldehyde dehydrogenase - Acetyl-CoA synthetase turns it into Acetyl CoA

Answer 277

-No regulation of ethanol metabolism -Ethanol oxidised in preference to other nutrients (for example the TCA cycle is run entirely from ethanol) -Results in high levels of NADH + H , high levels of NAD+ -If we dont have enough NAD+ the TCA cycle is inhibited and we then wont be able to turn lactate back into pyruvate

Answer 278

-maintaining blood glucose -adrenaline and glucagon cause increase in glycogenolysis , GNG (gluconeogensis), lipolysis , glycerol for GNG -Cortisol causes protein degradation and increase in GNG

Answer 279

-Not eating for a couple of days = cortisol is released , protomotes protein degradation , to greatly increase gluconeogenesis

Answer 280

-(1)blood glucose levels start to drop, detected by pancreas + release of glucagon to the liver , liver breaks down glycogen -pancreas release glucagon , stimulates the liver to produce glycogen -adrenaline release , by adrenal medulla, mimicking what the glucagon is doing -adipose tissue release FA to rest of body , liver can make glucose from the glycerol -cortisol now released from the adrenal cortex , muscle is forced to break itself down to release AA - alanine , alanine is a source of glucose

Answer 281

-switch of glycogen synthase , switch on phosphorylase , boost PFK2 -switch off glucogenesis , switch on glycogenolysis and glycolysis

Answer 282

-boost in lipoprotein lipase , increase in FA intake

Answer 283

Triglycerides in adipose tissue -Increase in HS lipase , increase in lipolysis

Answer 284

-stopping synthesis of glycogen , decrease in glycogen synthase , switch off glycogenesis -increase phosphorylase Decrease PFK2 , want to stop it doing glycolysis -increase in F-1,6-bisphosphatase , switch on gluconeogenesis

Answer 285

-decrease in Acetyl CoA , decrease in FA synthesis

Answer 286

-stop glycolysis from happening ( decrease in glucokinase) - pyruvate kinase also stopped Increase in PEP carboxykinase -increase in F1,6 bisphosphatase -increase in G-6-phosphatase , all about boosting gluconeogenesis

Answer 287

-switch of Acetyl CoA -boost in Carnitine , helps FA get into mitochondria

Answer 288

-cortisol only effects enzyme levels , slower longer term effect -boosting PEP carboxylase , AA catabolizing enzymes , enzymes to do with gluconeogenesis -Boost urea enzymes -boost in glycogen synthase (boost on glycogenesis ) - this is the first contradiction , promotes creation of glycogen , so liver can fill up with glycogen to support the need for it

Answer 289

-boost in HS lipase (increase in glycerol , FA)

Answer 290

Muscle -protein degradation -Transmaniation causes an increase in alanine , increase in GNG

Answer 291

-we now need to preserve functional protein -we have to drop the glucose requirements , body has to adapt to this -brain converts to Ketone body use (70% of energy used from KB, 30% used from glucose ) -reduced need for GNG - gluconeogenesis -Reduced need for protein catabolism

Answer 292

-ketone bodies

Answer 293

-atp , creatine phopshate , glucose

Answer 294

-with longer durations , we produce lactate now -lactate builds up , becomes a signal against exercise -muscles have to switch between two states depending on the two types of exercise

Answer 295

ADP+ creatine P = ATP + creatine ( creatine kinase) ADP+ADP = ATP + AMP (adenylate kinase) -this is the idea of the quick top up of ATP , using adenylate kinase and creatine kinase

Answer 296

-low lactate production -increased FA use -increased TG in muscles -more mitochondria

Answer 297

1)shivering 2)uncoupled respiration -thermogenin (UCP1) -Fatty acyl amino acids

Answer 298

Small hibernating animals have brown adipose tissue -modified adipocytes which generate heat by wasting energy in store fats

Answer 299

-numerous small TG droplets -more mitochondria -sympathetic innervation (noradrenaline)

Answer 300

-activates the uncoupling of protein 1 (UCP1) -leading to the uncoupling of the ETC and ATP synthesis energy is wasted as heat rather than captured at ATP

Answer 301

-UCP1 allows electrons to come in through a different route , FA bind to UCP1 and allow proteins in , energy is now lost as heat -thermogenin/UCP1 activated by FFA -ETC speeds up -UCP1 exerts into the membrane and allows the protons to come in through a different route -FA get released and bind to the UCP1 and this opens the channel and lets protons in -Energy not captured as ATP =now lost as heat , ETC speeds up , rate limiting step of ATP synthase has now gone

Answer 302

-numerous small TG droplets -more mitochondria -sympathetic innervation (noradrenaline)

Answer 303

-release into the blood of N-acyl amino acid synthase -joining of fatty acid + amino acid to make an N-acyl amino acid

Answer 304

-it interferes with the ATP/ADP carrier (translocase) -There is now an ATP/ADP carrier (translocase ) proton leak - Acyl amino acid binds to this and alters its shape and allows protons through , creates a gap -dont get ATP made due to short circuit , energy lost captured , lost as heat and ETC speeds up

Answer 305

-move protons across mitochondrial membrane without them going through the ATP synthase -This is very easily lethal , as it hits every mitochondria so every mitohoncdria releases heat not makes ATP

Answer 306

-In a healthy situation : the muscle liver and adipose tissue are the ones that respond to insulin , muscle will take up glucose , liver will turn it into glycogen and adipose tissue will turn glucose into FA Insulin resistant situation : -muscle stops taking up glucose -liver still takes up glucose , but no limit on it releasing glucose , liver will release glucose even if levels are too high -only tissue left is adipose tissue which soaks up all of the excess glucose , causes swelling

Answer 307

Types of mutation : point mutations (substitution - change sequence of gene)+ insertion/deletion mutations (can make DNA larger or shorter)

Answer 308

Causes of mutations -Replication errors-spontaneous: Normal replication introduces the wrong base once every 10 to the power of 10 base pairs , theres a good chance it will get repaired -some repetitive regions cause slippage of the polymerase and insertion of more repeats ,gene gets bigger and it cant be repaired

Answer 309

Spontaneous - tautomeric shifts -naturally occurring –spontaneously rearrange itself -shifted form binds G instead of A (wrong base is put in on strand) -not a permanent thing -each base can change to imino / enol form -Any mistake will be consolidated on next round of replication (A-C can be detected and repaired ) -MUtation will become a problem if theres another round of replication -number of hydrogen bonds changed -145

Answer 310

spontaneous:Replication errors Tautomerization Deamination depurination induced: Intercalating agents Base analogues Deaminating agents Alkylating agents Oxidising agents Radiation, U/V

Answer 311

Deamination -loss of amino group -changes the base -number of hydrogen bonds changed -100 of our C is changed to U per cell per day C changed to uracil A changed to inosine G changed to Xanthine -All of these should not be in DNA so are recognised and will be repaired -5-Methyl-C turned to T which cant be repaired , as its a normal base to be present in DNA

Answer 312

Depurination -losing the entire part of the nucleotide -cleavage of base-sugar bond -end up with an abasic site -Loss of G from strand , ends up with a random mutation introduced (The A is introduced randomly as theres no base to gte the correct match so cant match with the G) -10,000 purine in the cell a day are going to experience this -Mutation consolidated on next replication

Answer 313

Intercalating agents-Mutagens -Insert themselves between bases -Causes either insertion or deletion -The insertion will cause a complementary base (G-C) –Intercalated agent will insert itself and integer with replication process -intercalated disc = diamond emoji in photo

Answer 314

-Base analogues -chemicals that look like normal nucleotides -do the same thing but arent the same thing -incorporated into dna Problem: when it is in DNA its more prone to tautomeric shifts

Answer 315

Alkylating agents -add alkyl groups to nucleobases -chemicals that cause this for example are nitrosamines and Methyl bromide -Add a methyl group to G and it now pairs to T , which it shouldnt -Can now form only 2 hydrogen bonds , cant pair to C anymore , side affect is that it speeds up depurination , makes it more likely G will fall off all together

Answer 316

-remove Amino acids -all of the bases lose their amino groups -far quicker than spontaneous deamination -Example , nitrous acid made from nitrosamines , nitrite and nitrate

Answer 317

Example-superoxide ion , H202 -cause of most mutations -many possible nucleotide alterations -base pairs to A instead of G

Answer 318

-break bonds and create free radicals -bases on DNA chemically altered , linked or detached -leading source of mutagens -number of mutations directly proportional to radiation dose

Answer 319

Protein deficiency / excess : because the mutation occurs in a regulatory region of gene ,end up with low/high enzyme activity Protein dysfunction : because mutation occurs in intron/exon boundary , or mutation in coding region of gene (changes which amino acid it is ) , results in no / low or unregulated enzyme activity

Answer 320

-Anabolic= cant make something , end up with a deficiency -catabolic = lose ability to get rid of something , metabolite F builds up , excess of metabolite F -Storage = cant breakdown stores ,cellular deposits of macromolecule X (build up ) but also have a deficiency of monomers but monomers arent made

Answer 321

Inborn errors of metabolism (IEMS) -First inborn error of metabolism : alkaptonuria -Loss of an enzyme leads to a build-up of a metabolite which is excreted in the urine -urine turns black on exposure to air

Answer 322

PKU= excess / build up of phenyl-ketones in urine -Enzyme affected Phenylalanine Hydroxylase -normally phe converted to Tyr -Phe builds up if not converted to Tyr -Phe goes into blood , blood levels go up -Liver will attempt to convert phe to phenyl pyruvate and then from that the other molecules (blue ) which can be lost in urine -recessive disorder -comes in various types , most due to point mutations -40% in intron/exon splice sites -20% of mutations found in coding regions -Other PKU( types 4 and 5 ) are not due to PAH , theyre due to dihydropteridine reductase IEMS:phenylketonuria (PKU) -Disease progress -PKU manifests after birth -During pregnancy mother breaks down Phe -Neonate develops hyperphenylalaninemia after a few days of eating protein Consequences : mental retardation , organ damage , unusual posture -Sufferer just be put on a low phenylalanine diet

Answer 323

-14 different types : autosomal recessive -various enzymes known to be affected: phosphorylase , debranching enzyme , branching enzyme -inability to convert glycogen to glucose (cant use glycogen stores) Consequences : enlarged liver (glycogen builds up in liver ) and hypoglycemia

Answer 324

Absence of glucose-6-phosphate = no glucose released into the blood Appears in early childhood Sweating , poor growth , muscle weakness Treatment: regular glucose drinks Naso-gastric drip overnight

Answer 325

Absence of phosphorylase in muscle = no glycogen usage by muscles Basically normal , except when exercising Pain in muscles due to damage in muscles ; urine looks like wine due to breakdown of muscle

Answer 326

NADH-Q reductase (Complex I): Electrons are first donated by NADH to NADH-Q reductase (Complex I). This complex transfers the electrons to ubiquinone (CoQ) and pumps protons across the inner mitochondrial membrane. Ubiquinone (CoQ): Ubiquinone (CoQ) is a mobile electron carrier that picks up electrons from Complex I (or Complex II) and carries them to the next complex, Q-cytochrome c oxidoreductase (Complex III). Q-cytochrome c oxidoreductase (Complex III): Q-cytochrome c oxidoreductase (Complex III) receives electrons from ubiquinone and passes them to cytochrome c while also pumping protons across the membrane. Cytochrome C: Cytochrome C is a small, soluble protein that shuttles electrons from Complex III to cytochrome c oxidase (Complex IV). Cytochrome C oxidase (Complex IV): Cytochrome c oxidase (Complex IV) receives electrons from cytochrome c and transfers them to molecular oxygen (O₂), reducing it to water (H₂O). This step also pumps protons across the membrane.

Answer 327

Hexokinase/Glucokinase (Step 1): Reaction: Glucose → Glucose-6-phosphate (G6P) This step is irreversible because it involves the phosphorylation of glucose, which traps it inside the cell and commits it to glycolysis. It consumes one ATP molecule. Phosphofructokinase-1 (PFK-1) (Step 3): Reaction: Fructose-6-phosphate → Fructose-1,6-bisphosphate This is a key regulatory step in glycolysis. The enzyme phosphofructokinase-1 (PFK-1) is highly regulated and commits the intermediate to continue through glycolysis. This step also consumes one ATP molecule. Pyruvate Kinase (Step 10): Reaction: Phosphoenolpyruvate (PEP) → Pyruvate This is the final step in glycolysis, where ATP is generated. The conversion of PEP to pyruvate is irreversible and is catalyzed by pyruvate kinase. This step produces one ATP and one pyruvate molecule.

Answer 328

HDL (High-Density Lipoprotein) – Smallest and densest LDL (Low-Density Lipoprotein) IDL (Intermediate-Density Lipoprotein) VLDL (Very Low-Density Lipoprotein) Chylomicron – Largest and least dense

Answer 329

Glucose – Smallest Glycerol Fatty Acid (FA) Triglyceride Glycogen – Largest

Answer 330

palmitic acid,glycerol,ethanol,acetoaetate

Answer 331

Adipose Triglyceride Lipase (ATGL) TAG (Triacylglycerol) Initiates lipolysis by converting TAG → DAG Hormone Sensitive Lipase (HSL) DAG (Diacylglycerol) Converts DAG → MAG Monoglyceride Lipase (MGL) MAG (Monoacylglycerol) Final step: MAG → glycerol + free fatty acid

Answer 332

-protein deficiency /excess ; when theres mutation in regulatory regions of gene , low high / enzyme activity -protein dysfunction;when theres a mutation in intron/exon boundary , mutations in coding region of gene ,when you have no low or unregulated enzyme activity

Answer 333

1-tissue sample 2-chromosomal DNA extracted 3-DNA analysed for known /unknown mutations

Answer 334

Amniocentesis is a prenatal test where a sample of amniotic fluid, the fluid surrounding the baby in the womb, is taken for testing

Answer 335

-Chorionic villus sampling(8-12th week) ;chorion is embryonal , risk of contamination by maternal tissue/damage

Answer 336

Screening:detect known mutations Use oligonucleotide probes/PCR primers Analysis;define unknown mutation-using PCR / sequencing

Answer 337

Screening:detect known mutations Use oligonucleotide probes/PCR primers Analysis;define unknown mutation-using PCR / sequencing

Answer 338

-detect known mutation -custom oligonucleotide designed -binds to known mutant sequence , but not the normal gene sequence -can be used on DNA blots or as a primer for a PCR eg-ARMS(amplification refractory mutation system)

Answer 339

Detects size changes due to insertions/deletions -detects homo/heterozygous can only PCR up to 3000b.p -cant detect substitution mutations -large amounts of DNA , bands can be cut out and used for sequencing

Answer 340

homozygous

Answer 341

Step 1 = prepare the corrective DNA/RNA put gene into plasmid vector step 2= gene transfer , either in vivo or ex vivo

Answer 342

in vivo : -require injection -easy to re-treat -needs specific targeting -may have immune complications ex vivo -requires surgery -little wastage -no need for targeting -no immune system

Answer 343

-transported in blood -Small -Specific target -Avoid endosome degradation -Translocate DNA into nucleus

Answer 344

-Transfect cell= DNA in cell -Then translocates into nucleus -Then transcribed into mRNA -then translacated back out and then translated into protein -can now make metabolite B

Answer 345

first three are only EX vivo) -injection -DNA bullet -take metal beads and coat with DNA ,take flask of cells and fire beads at cells ,some will end up in nucleus -Artificial chromosomes multiple genes ,no insertional mutations,no toxicity/immune rejection,long duration -Liposomes (in vivo/ex vivo) need to get liposome inside the cell ,may fuse with plasma membrane and release its content

Answer 346

-non -specific uptake - mostly endothelial -attacked by serum proteins ; disruption , labelled for phagocytosis by WBC -In cell , destroyed by lysosomes

Answer 347

prons -gets into nucleus -gets into cells -gets expressed cons -toxicity -immune response -limited duration -small inserts -insertional mutagensis (retroviruses)

Answer 348

-adenovirus ; limited cell types , short duration -adeno-associated virus ; wide variety of cells -retrovirus ;integrate genes into genome , inly infect dividing cells -lentivirus ; wide variety of cells , can infect non-dividing cells

Answer 349

-Chemically interfering with cellular/biological systems to enhance , modify or block activity

Answer 350

-Compounds which interact with biological functions , changing them , they have direct effects on the treatment and prevention of disease and the amelioration (improvement) of suffering

Answer 351

Pharmacodynamics ; specific to drug - the action of the drug Pharmacokinetics non specific -drug handling (how the drug is being treated by our body)

Answer 352

1-in vitro studies 2-animal testing 3-clinical testing 4-marketing

Answer 353

-reversible blockade of physiological responses -regulation of normal physiological responses -supplementation of normal physiological processes -elimination of non self(antibacterials)

Answer 354

Most experiments are performed on isolated tissues The most common preparation is the guinea pig ileum

Answer 355

-can be reversible (non-covalent) or irreversible (covalent) -An ideal drug will be selective for a particular response

Answer 356

-Agonist; drug that produces a response -Antagonist;a drug that blocks a response , has no action of its own -Pharmacological-prevent the action of an agonist at its own receptor -Physiological -agents which have mutually antagonistic responses but act through different receptors

Answer 357

-agonist; drug that produces a response by binding and introducing a change to an active configuration which produces a response -Antagonist; a drug that blocks a response by binding to the same sites but doesnt induce an active conformation by binding it prevents access to the agonist

Answer 358

-covalently bind to the agonist binding site -effect cant be overcome by the addition of more agonist -reduce the maximum response

Answer 359

-a receptor agonist has affinity for the receptor and intrinsic activity

Answer 360

-a receptor antagonist has affinity for the receptor but no intrinsic activity

Answer 361

-Acetylcholine (100) , proprionyllcholine(400) butyrylcholine(150) valverylcholkine(30) all are full agonists Muscarine is not an agonist at these receptors , instead,they are activated by nicotine These are blocked by atropine

Answer 362

;acetylcholine(100),proprionyllcholine(5) butyrylcholine(partial agonist) valverylcholkine (antagonist) The different order suggest that acetylcholine is acting via a different receptor - not activated by muscarine but by nicotine added notes; These two types are known as muscarinic and nicotinic receptors , acetylcholine is the natural agonist at both types The existence of multiple receptor subtypes for an agonist gives the possibility that it may be possible to selectively target one or other is an extremely important pharmacological concept

Answer 363

-type of acetylcholine receptor -theyre g-protein coupled receptors -found in intestinal smooth muscle ,heart,blood vessels , salivary glands,CNS -activated by muscarine , blocked by atropine

Answer 364

-ligand-gated ion channel -found in skeletal muscle , ganglia , CNS.Pentameric structure , ligand gated sodium channels with many different subunit combinations -neuronal nicotonic receptors have different combinations of alpha and beta -there are at least 8 alpha and four beta subtypes -which have subtly different channel opening times

Answer 365

decamethonium antagonist at NMJ , hexamethonium antagonist at ganglia

Answer 366

-a tyrosine kinase receptor -binding of insulin results in a conformational change of insulin receptor which activates the tyrosine kinase catalytic domain -has two subunits -found on the surfaces of most cells in the human body

Answer 367

-Nuclear receptor -Intracellular receptors are transcription factors that intercat with DNA in the nucleus and regulate gene expression -Found throughout the body including cells of the brain,liver,muscle ,immune system,adipose tissue

Answer 368

-H1 blocked by mepyramine , produces vasodilation and increased vascular permeability H2-stimulate gastric acid secretion blocked by cimetidine H3-presynaptic receptors

Answer 369

;ligand-gated ion channels ,G protein coupled receptors,kinase-linked and related receptors and Nuclear receptors

Answer 370

-influences its selectivity , stability and its other properties

biochem s2 Flashcards

(426 cards)