Metabolism Flashcards
L13 L14 L15 L16 L17 L18 L19 (103 cards)
1
Q
What are aldoses and ketoses?
A
Aldoses: Monosaccharides which are aldehydes
Ketoses: Monosaccharides which are ketoses
2
Q
How do pyranoses form?
A
When monosaccharides are in solution, carbon sugars form ring structures spontaneously. Outside of solution, they’re straight chains.
3
Q
What is the orientation of the Alpha and Beta glucose -OH groups?
A
Alpha- DDUD
Beta- UDUD
‘Alpha isnt capital so is a DDUD. Beta is capital so makes me go UDUD’
4
Q
What are epimers?
A
An epimer is a stereoisomer where the penultimate carbon of the straight sugar chain has a different position of the -OH group.
There are D-isomers and L-isomers
5
Q
What are anomers?
A
An anomer is a stereoisomer where the first carbon of a cyclical monosaccharide has different positions for the -OH group.
There are alpha and beta isomers.
6
Q
What is a pyranose?
A
Collective term for polysaccharides with a ring formation with and oxygen in the ring and 5 carbons.
7
Q
Definition of metabolism.
A
‘The totality of chemical reactions and physical change that occur in living organisms, comprising of anabolism and catabolism.’
8
Q
What is catabolism?
What is anabolism?
A
Catabolism: Metabolic breakdown of complex substances into smaller products. Generates ATP and NADH
Anabolism: Energy requiring part of metabolism where simpler substances are transformed into more complex ions. Uses ATP and other triphosphate nucleotides.
9
Q
What is stepwise breakdown and why is it used?
A
Instead of the entire sugar combusting at once, smaller combustions take place.
It ensures that not all energy from sugar is used and lost immediately. Energy at each step is stored in activated carrier molecules.
https://slideplayer.com/slide/8259822/25/images/14/Harnessing+Energy+-+Stepwise+Breakdown+of+Carbohydrates.jpg
10
Q
Why is ATP hydrolysis favourable?
A
There is electrostatic repulsion betweem the phosphate groups which is revealed when Pi is removed from ATP. Additionally there is +ve entropy.
11
Q
How much energy is released when ATP is hydrolysed to ADP?
How much energy is released when ATP is hydrolysed to AMP?
A
-31 to -50 kJ/mol
Doubled when ATP is hydrolysed to AMP
12
Q
What do NAD and FAD stand for?
A
Nicotinamide adenine dinucleotide
Flavin adenine dinucleotide
13
Q
What is a futile cycle?
A
When there are reversible reactions which cause product to be reverted back to reactant.
14
Q
Pyruvate structure
A
https://pubchem.ncbi.nlm.nih.gov/image/imgsrv.fcgi?cid=107735&t=l
15
Q
Lactate structure
A
https://pubchem.ncbi.nlm.nih.gov/image/imgsrv.fcgi?cid=91435&t=l
16
Q
What are thioester bonds?
A
Thioester bond: R-CO-S-R’
17
Q
Why is glycogen a better fuel source than glucose?
A
Glycogen is low in osmolarity but glucose is osmotically active because there are more molecules.
18
Q
What enzyme is used for glycogen synthesis and breakdown?
A
Synthesis: Glycogen synthase
Breakdown: Glycogen phosphorylase
19
Q
How is glycogen synthesised?
4 Steps
A
Glucose + ATP –(Glucokinase/hexokinase)–> Glucose 6-phosphate + ADP
Glucose 6-phosphate <=(Phosphoglucomutase)=> Glucose 1-phosphate
Glucose 1-phosphate + UTP –(UDP glucose pyrophosphorylase)–> UDP glucose + PPi
UDP glucose + glycogen [n glucose] –(Glycogen synthase)–> glycogen [n+1 glucose] + UDP
20
Q
How is glycogen broken down?
Chemical reactions
A
Glycogen [n glucose] + phosphate group –(glycogen phosphorylase)–> Glucose 1-phosphate + glycogen [n-1 glucose]
Glucose 1-phosphate –(Phosphoglucomutase)–> Glucose 6-phosphate
Glucose 6-phosphate + H2O–(Glucose 6-phosphatase)–> Glucose + phosphate group
21
Q
What is the net yield of ATP from glycolysis?
A
2 ATP
22
Q
How is glycogen metabolism regulated?
A
Hormones binds cell surface receptor and activates internal signalling pathway.
Internal signalling activates a protein kinase.
Glycogen synthase is inhibited by phosphate group.
Glycogen phosphorylase is activated by phosphate group.
23
Q
What is feedback inhibition?
A
When the product of a reaction inhibits the enzyme responsible for the reaction.
24
Q
What does phosphofructokinase do? How is it inhibited?
A
Catalyses Fructose 6-phosphate to Fructose 1,6-biphosphate
ATP inhibits the enzyme
25
Where in the cell does the 'link reaction' occur?
The matrix of the mitochondria
26
TCA cycle
https://www.researchgate.net/profile/Justine_Couper/publication/28800358/figure/fig3/AS:798422542086144@1567370176387/5-The-Krebs-Cycle-Tricarboxylic-Acid-Cycle-TCA-Cycle-Metabolic-pathways-for.png
27
Which reactions of the TCA cycle are irreversible?
What are the enzymes?
Why?
```
Step 1 (citrate synthase)
Step 3 (isocitrate dehydrogenase)
Step 4 (α-ketoglutarate)
```
Don't know about step 1, but step 3 and 4 produce CO2 which means theres +ve entropy
28
How is the TCA cycle is regulated?
Feedback inhibition of key enzymes (citrate synthase)(isocitrate dehydrogenase) (alpha-ketoglutarate)
29
What is anaplerosis?
Anaplerosis is the replenishing TCA cycle intermediates that have been extracted for biosynthesis.
30
How are 'new' molecules for the TCA cycle made?
Pyruvate --(pyruvate carboxylase)--> oxaloacetate
| Pyruvate <==(Malic acid)==> Malate (malic acid only used for backwards reaction)
31
NAD+ and NADH structure
https://i.pinimg.com/originals/e2/a3/6c/e2a36c116cd8c2450d11e28229b4061a.jpg
32
NADP+ structure
https://www.researchgate.net/profile/Rui_Huang11/publication/307613193/figure/download/fig3/AS:402989975130118@1473091705321/Chemical-structures-of-NADP-and-NAD-Structures-of-NADP-and-NAD-were-shown-and-the.png
33
FAD structure
https://www.researchgate.net/profile/Sergio_De_Nicola/publication/51873284/figure/fig1/AS:213801812140036@1427985732028/Structural-formula-of-flavin-adenine-dinucleotide-FAD.png
34
Where does oxidative phosphorylation take place?
The inner mitochondrial membrane
35
What are the components of the ETC?
Flavin cofactors and Coenzyme Q (Hydrogen acceptors)
Iron Sulfur proteins and cytochrome proteins (Electron acceptors)
36
Structure of CoQ?
https://www.researchgate.net/profile/Srinivasan_Shanmugam/publication/247916115/figure/fig1/AS:298359173730304@1448145778093/Chemical-structure-of-coenzyme-Q10.png
37
What is the function of Iron-Sulfur proteins?
Proteins within protein complexes in the ETC that contain Fe-S clusters. They're capable of redox reactions so they transport electrons along the ETC.
38
What is the function of cytochrome proteins?
Cytochromes are proteins containing haem groups as a cofactors, that perform electron transfer reactions and catalysis by reduction or oxidation of their haem iron.
39
What is the arrangement of the proteins in the ETC?
Flavin -> CoQ -> cyt b -> cyt c -> cyt a
40
What is ubiquinone?
Otherwise known as Coenzmye Q.
| It is the intermediate molecules between protein complex I and III
41
What is gluconeogenesis?
Making glucose in catabolic reaction from non-carbohydrate precursors. Most amino acids are capable of gluconeogenesis.
42
How do you make glucose from fats/lipids?
You can't
43
Oxalic acid structure
https://www.chemsynthesis.com/molimg/1/big/14/14653.gif
44
Succinic acid structure
https://www.sigmaaldrich.com/content/dam/sigma-aldrich/structure2/010/mfcd00002789.eps/_jcr_content/renditions/mfcd00002789-medium.png
45
Malonic acid structure
https://www.sigmaaldrich.com/content/dam/sigma-aldrich/structure4/180/mfcd00002707.eps/_jcr_content/renditions/mfcd00002707-medium.png
46
Glutaric acid structure?
https://image.chemsrc.com/caspic/100/110-94-1.png
47
What is pyrophosphate?
(PPi)
| A product of ATP -> AMP which will be hydrolysed into 2Pi
48
An enzyme that adds a phosphate is typically known as?
Kinase or phosphorylase
49
An enzyme that removes a phosphate is typically known as?
Phosphatase
50
What is the function of NADP?
Needed for synthetic reactions (fatty acids, steroids) and drug metabolism.
51
How is glycogen in the liver used?
| How is glycogen in the muscle used?
Liver: is sensitive to changes in blood glucose concentration. Its acts under the effects of glucagon or insulin in order to maintain blood glucose concentration
Muscle: uses the glycogen stored for respiration
52
What are the similarities and differences between hexokinase and glucokinase?
Similarities: They both catalyse Glucose -> Glucose 6-phosphate
Differences:
- Hexokinase is found in all cells of the body except for liver and pancreatic β cells whereas Glucokinase is found only in liver cells and pancreatic β cells.
- Hexokinase has a high affinity for glucose and a low Vmax whereas Glucokinase has a low affinity for glucose and a high Vmax.
- Hexokinase is inhibited by glucose 6-phosphate (feedback inhibition) and glucokinase is inhibited by insulin
- Because of their Vmax , affinity for glucose and inhibitors, glucokinase is used usually after a large meal to rapidly convert glucose and hexokinase is used to 'gradually' convert glucose until enough has been converted in glycogen
53
Where is insulin released from?
| Where is glucagon released from?
Glucagon: Pancreatic α cells
Insulin: Pancreatic β cells
54
What are the reactions of glycolysis?
| Each step, enzyme and chemical reaction.
1) Glucose -> Glucose 6-phoshphate (catalysed by hexokinase/glucokinase)
2) Glucose 6-phosphate <=> Fructose 6-phosphate (catalysed by phosphohexose isomerase)
3) Fructose 6-phosphate -> Fructose 1,6-bisphosphate (catalysed by phosphofructokinase)
4) Fructose 1,6-bisphosphate <=> 2x Glyceraldehyde-3-phosphate (catalysed by aldolase)
5) Glyceraldehyde-3-phosphate <=> 1,3- bisphophoglycerate ( catalysed by Glyceraldehyde-3-phosphate dehydrogenase)
6) 1,3- bisphophoglycerate <=> 3-phosphoglycerate (catalysed by 3-Phosphoglycerate kinase)
7) 3-Phosphoglycerate <=> 2-Phosphoglycerate (Phosphoglycerate mutase)
8) 2-Phosphoglycerate <=> Phosphophenolpyruvate (catalysed by enolase)
9) Phosphophenolpyruvate -> Pyruvate (catalysed by pyruvate kinase)
ATP, Pi, NAD+ and H2O not shown
55
Which reactions of glycolysis are irreversible?
The first, third and ninth(last) reactions
1) Glucose + ATP -> Glucose 6-phoshphate + ADP (catalysed by hexokinase/glucokinase)
3) Fructose 6-phosphate + ATP -> Fructose 1,6-bisphosphate + ADP (catalysed by phosphofructokinase)
9) Phosphophenolpyruvate + ADP -> Pyruvate ATP (catalysed by pyruvate kinase)
56
What is significant about fructose 1,6-bisphosphate to glyceraldehyde-3-phosphate in glycolysis?
The full reaction:
Fructose 1,6-bisphosphate <=> Glyceraldehyde-3-phosphate + Dihydroxyacetone phosphate (catalysed by aldolase)
Dihydroxyacetone is not used in glycolysis so is converted to glyceraldhyde-3-phosphate by the actions of triose phosphate isomerase
57
Where do erythrocytes get energy from?
Anaerobic respiration, because they don't have mitochondria.
58
What are glucogenic amino acids?
What are ketogenic amino acids?
Which amino acids are glucogenic, ketogenic or both?
Glucogenic amino acids have the potential to be converted into glucose
Ketogenic amino acids have the potential to be converted into ketone bodies
https://upload.wikimedia.org/wikipedia/commons/thumb/1/16/Amino_acid_catabolism_revised.png/450px-Amino_acid_catabolism_revised.png
59
In oxidative phosphorylation, what is within protein complex I, III and IV?
Protein complex I (NADH dehydrogenase complex): FMN (Flavin mononucleotide) and Fe-S clusters
Protein complex III (cytochrome c reductase complex):
Fe-S cluster, one c1 cytochrome and two b cytochromes.
Protein complex IV (cytochrome c oxidase complex):
two Copper ions, cytochrome a and cytochrome a3
60
In oxidative phosphorylation, what is the function of protein complex II?
Otherwise known as Succinate-Q oxidoreductase or Succinate dehydrogenase.
It is an enzyme part of both the TCA cycle and ETC.
It catalyses Succinate to Fumarate in the TCA cycle; the FAD that is reduced to FADH2 in the TCA is embedded in protein complex II.
61
In oxidative phosphorylation, what is the function of protein complex V?
It is ATP synthase, so synthesises ATP from ADP and Pi utilising energy from H+ diffusing from intramembranal space to the matrix of the mitochondria.
62
In oxidative phosphorylation, what is the function of protein complex I?
This protein complex contains FMN which oxidises NADH and H+ to NAD+.
2 electrons are added to FMN (and it goes to its reduced form of FMNH2), and then travel through a series of Fe-S clusters. The electrons are transferred finally to a ubiquinone molecule in the membrane.
As the electrons travel along the complex, 4 protons are pumped into the intermembrane space from the matrix.
63
Give two mechanisms by which these fatty acids can be utilised as an energy source by the body.
By generation of ketone bodies.
| By β-oxidation
64
Which tissue/organ cannot metabolise ketone bodies?
The liver
The liver makes ketone bodies to provide for other organs/tissues. If the liver was able to metabolise ketone bodies, it would be a futile cycle.
The way that liver is adapted to this is by not having any enzymes to metabolise ketone bodies
65
Why can humans convert glucose into fat but not fat into glucose.
Glucose can go through glycolysis and the link reaction to make Acetyl CoA and if energy is plentiful, acetyl CoA can go on to form fatty acids.
The link reaction is not reversible however.
Therefore, even though fatty acids can be broken down into Acetyl CoA, the link reaction is what stops the Acetyl CoA being able to go back to glucose.
66
In which organ does the synthesis of urea take place?
The liver
67
What amino acids can be used to form oxoacetalate?
Aspartate
| Aspargine
68
What amino acids can be used to form α-ketoglutarate?
Glutamate
Additionally, Argine, Proline, Histdine and glutamine can form glutamate so technically these 4 amino acids can also form α-ketoglutarate.
69
What amino acids aren't capable of gluconeogenesis? Why aren't theses amino acids capable of gluconeogenesis?
Lysine and Leucine are the only amino acids which arent capable of gluconeogenesis.
They can only form ketone bodies (Acetyl CoA), so aren't able to form glucose.
70
What are ketone bodies?
They are water-soluble molecules containing ketones. They are produced by in the liver and ketone bodies are produced by fatty acids (or certain amino acids) in periods of fasting.
71
What can the brain metabolise?
The brain metabolises glucose under normal circumstances, but in starvation, the brain produces enzymes able to metabolise ketone bodies.
72
How are fatty acids broken down?
| What enzymes are used?
Triacylglycerol --(triacylglycerol lipase)--> Diacylglycerol + fatty acid
Diacylglycerols --(DAG lipase)--> Monoacylglycerol + fatty acid
Monoacylglycerol --(MAG lipase)--> Glycerol + fatty acid
73
What happens to the glycerol after the fatty acid has been broken down?
Under normal circumstances, the glycerol enter muscle tissues where they enter the glycolysis pathway to be converted to pyruvate, where they then go through the TCA cycle.
In starvation, the glycerol enter the liver where they are converted to glucose by gluconeogenesis.
74
What does albumin do for fatty acids?
They transport fatty acids that were broken down from triacylglycerols through the plasma.
75
How do fatty acids enter the mitochondria?
Fatty acids must first bind to Coenzyme A
Fatty acid + CoA + ATP --(Fatty acyl-CoA synthetase)--> Fatty acyl-CoA + AMP + PPi
Fatty acyl-CoA enters the intermembrane space because the outer mitochondrial membrane is leaky.
Fatty acyl-CoA + Carnitine --(Carnitine palmyitoyl transferase I)--> CoA + fatty acyl-Carnitine
The fatty acyl-carnitine is transported into the matrix via translocase in the inner mitochondria membrane.
Fatty acyl-Carnitine Fatty acyl-CoA + CoA --(Carnitine palmyitoyl transferase II)--> Carnitine + Fatty acyl-CoA
76
How is Acetyl CoA formed from fatty acids?
Once inside the mitochondria matrix:
1) Fatty acyl-CoA + FAD --(acyl-CoA dehydrogenase)--> Enoyl-CoA + FADH2
2) Enoyl-CoA + H2O --(Enoyl-CoA hydratase)--> Hydroxyacyl-CoA
3) Hydroxyacyl-CoA + NAD+ --(Hydroxyacyl-CoA dehydrogenase)--> β-Ketoacyl-CoA + NADH + H+
4) β-Ketoacyl-CoA + CoA --(β-Ketoacyl-CoA thiolase)--> Acetyl CoA + Fatty acyl-CoA (which is 2C shorter than the original fatty acid)
77
What happens to odd numbered fatty acids? (as in a fatty acid which has an odd number of carbons)
Once the fatty acid has been broken down to its last three carbons, Propionyl-CoA will have formed (CH3-CH2-CO-S-CoA)
1) Propionyl-CoA + CO2 --(Propionyl-CoA carboxylase utilising ATP hydrolysis)--> Methylmalonyl-CoA (COOH-CH2-CH2-CO-CoA)
2) Methylmalonyl-CoA --(Methylmalonyl-CoA mutase)--> Succinyl-CoA
Succinyl-CoA can just be put straight into the TCA cycle
78
What is protein turnover?
The renewal/replacement of proteins in the body.
Structural proteins have half lives of years so they last for quite a while, but hormone and enzymes have half lives of minutes so need to regularly be replaced
79
What is the amino acid pool?
Its a mixture of amino acids available in the cell derived from dietary sources or degradation of proteins.
80
What are essential proteins?
Proteins which we cant make in our body, they have to be taken into the body via our diet. 10 of the amino acids are essential amino acids
81
What is nitrogen balance?
Nitrogen balance is the nitrogen intake compared to the nitrogen excretion.
Neutral nitrogen balance is [intake = excretion] and is considered healthy
Positive nitrogen balance is [intake > excretion] and is normal in pregnancy, after injury and during child growth
Negative nitrogen balance is [intake < excretion] and is present in starvation, during serious illness and durin injury. Uncorrected negative nitrogen balance will ultimately leas to death.
82
What happens is excess protein is taken in by the diet?
| What happens to the nitrogen balance?
The nitrogen balance remains the same because andy excess protein is catabolised and the nitrogen and excreted as urea.
83
What is deamination?
Removal of an amino groups
84
What is transamination?
When an amino acid exchanges amino groups with keto acid.
| Amino acid + keto acid 1 <==(amino transferase)==> keto acid 2 + amino acid 2
85
What is the function of the liver in N metabolism?
- removal of amino acids, glucose & fats from the portal blood supply
- absorbed amino acids used for synthesis of cellular proteins
- synthesis of plasma proteins
- synthesis of haem, purines & pyrimidines for DNA & RNA
- degradation of excess amino acids by transdeamination
- conversion of NH3 to urea for excretion
86
When is lactate produced and by what cells?
Anaerobic respiration for erythrocytes and muscle cells
87
Glutamate -> Glutamine?
| Glutamine -> Glutamate?
Glutamate + ATP + NH3 --(glutamine synthase)--> Glutamine + ADP + Pi
Glutamine + H2O --(glutaminase)--> Glutamate + NH3
88
Glutamate structure
https://pubchem.ncbi.nlm.nih.gov/image/imgsrv.fcgi?cid=4525487&t=l
89
Glutamine structure
https://cdn1.byjus.com/wp-content/uploads/2018/12/glutamine.png
90
What is the importance of glutamine?
Ammonia is toxic to the brain and glutamine is a safe carrier of ammonia in the blood. Glutamine can carry 2 ammonia equivalents to the liver for urea formation.
Additionally, glutamine can deliver ammonium ions to
the kidney for pH regulation (buffering H+).
91
```
Urea cycle
(structure not needed, just names)
```
NH4+ + CO2 + 2ATP --> carbamyl phosphate + 2ADP + 2Pi
carbamyl + ornithine --> cirtullline
citrulline + aspartate --> argininosuccinate
argininosuccinate --> arginine + fumarate
arginine --> urea + ornithine
92
What is the structure of carbamyl phosphate?
H2N-CO-Pi
93
What is the blood glucose concentration for:
1) physiological circulating glc concentration
2) average fasting
3) leads to coma and death
1) 3.9-6.2 mM
2) 4.4-5 mM
3) 2.5 mM or less
94
How many ATP molecules are produced from:
1) anaerobic respiration
2) aerobic respiration
3) fatty acid oxidation
1) 2 ATP
2) roughly 31 ATP
3) variable, calculated by ---> β-oxidation x 4 ATP (because 1 NADH (2.5 ATP) and FADH2 (1.5 ATP) per β-oxidation) + Acetyl CoA produced from β-oxidation x 10 ATP
95
What are advantages of glucose as a metabolic fuel?
| +Disadvantages?
+ water soluble, so can travel via bloodstream without a need for a carrier
+ can cross BBB
+ can be oxidised anaerobically
- relatively low yield of ATP compared to fatty acids
- osmotically active
- byproducts can damage cells if [glucose] is high
96
What is the main role of glucose in adipocytes?
Producing glycerol phosphate for triacylglycerol reassembly
97
What are the main sources of blood glucose?
Diet, liver glycogen and liver gluconeogenesis
98
Which glucose transporter is translocated to the cell membrane by action of insulin on muscle cells?
GLUT4
99
In gluconeogenesis, how are the irreversible glycolysis overcome?
Enzymes, reagents and reactions
Glycolysis: Glucose --> Glucose 6-phosphate
Gluconeogenesis: Glucose 6-phosphate + H2O --(Glucose 6-phosphatase)--> Glucose + Pi
Glycolysis: Fructose 6-phosphate --> Fructose 1,6- bisphosphate
Gluconeogenesis: Fructose 1,6-bisphosphate + H2O --(Fructose 1,6- bisphosphatase)--> Fructose 6-phosphate
Glycolysis: Phosphoenolpyruvate --> Pyruvate
Gluconeogenesis: Pyruvate + H2O + CO2 + --(Pyruvate carboxylase)--> oxaloacetate + ADP + Pi
oxaloacetate + GTP --(PEP carbokinase)--> phosphoenolpyruvate + CO2 + GDP
100
What is the glucose-alanine cycle?
Otherwise known as the Cori-cycle (recycling lactate from muscle or erythrocytes via conversion to glucose in the liver)
Lactate produced via anaerobic respiration is converted back to pyruvate
Lactate + NAD+ --(lactate dehydrogenase)--> Pyruvate + NADH + H+
101
What does insulin and glucagon do?
Insulin: anabolic horome that promotes synthesis of glycogen
Glucagon: catabolic hormone that promotes degradation of glycogen
102
What are the metabolic effects of insulin?
- Inhibition of gluconeogenesis in the liver
- Activation of glycogen synthesis for liver and muscle cells (glycogen synthase activated)
- Increased fatty acid synthesis and lipid assembly
- Increased AA uptake into cells and protein synthesis
- Increased glucose uptake in muscle by increasing glucose transporters (GLUT4)
103
What are the metabolic effects of glucagon?
- Increase in blood glucose by increasing glycogenolysis and gluconeogenesis in the liver
- Increase in circulating fatty acids and ketone bodies, increased adipose tissue lipolysis, fatty acid oxidation in the liver and ketone body formation.
- Increase uptake of AA by the liver for gluconeogenesis
