Metabolism II COPY Flashcards
1
Q
GLYCOGEN PATHWAYS
A
- Glycogen is a polysaccharide that is the main form of glucose storage
- Consists of a chain of glucose monomers connected by alpha-1,4-glycosidic linkages
- Also includes branches via alpha-1,6-glycosidic linkages (formed by different pathway)
- Glycogenolysis = breakdown of glycogen into glucose monomers
- Glycogenesis = glycogen synthesis = addition of glucose monomers to form polymer
2
Q
Glycogenolysis =
A
Glycogenolysis = breakdown of glycogen into glucose monomer
3
Q
Glycogenesis
A
= glycogen synthesis = addition of glucose monomers to form polymer
4
Q
Glycogenolysis 2
A
- Glycogenolysis = breakdown of glycogen into glucose monomers
- Glycogen is broken down into glucose-1-phosphate by glycogen phosphorylase
- Glucose-1-phosphate is converted to glucose-6-phosphate by phosphoglucomutase
- Glucose-6-phosphate can then enter glycolysis
5
Q
Glycogenesis 2
A
= glycogen synthesis = addition of glucose monomers to form polymer
• Glucose converted to glucose-6-phosphate
- G6P converted to glucose-1-phosphate by phosphoglucomutase
- G1P converted to UDP-glucose by uridyl transferase
- UDP-glucose is added to glycogen polymer by glycogen synthase
- Glucose addition requires a primer in the form of glycogen or glycogenin protein
- Storage of glucose as glycogen reduces solute load in cells
- Less water is required to solvate glycogen than millions of glucose molecules
- Storage as glycogen prevents spontaneous degradation of glucose
6
Q
Hormonal regulation of glycogen pathways
1.
A
- For blood-sugar homeostasis:
- Glucagon promotes glycogen breakdown
- Insulin promotes glycogen synthesis
7
Q
Hormonal regulation of glycogen pathways
- fight or flight
A
For fight-or-flight:
- Epinephrine stimulates glycogen breakdown
8
Q
Gluconeogenesis
A
- De novo synthesis of glucose
- Occurs mostly in liver
- Raises blood glucose levels
- Works in tandem with glycogen breakdown
- Can use pyruvate, lactate, glycerol, some amino acids as carbon sources
USED TO RAISE BLOOD SUGAR***
Not all cells do this, happens mostly in the liver. Happens at the same time probably as break down of glycogen* when haven’t eaten in a while, definitely breaking down glycogen, our next move would be to do gluconeogenesis
9
Q
Gluconeogenesis Steps
A
Many steps are same as in glycolysis but reverse direction=
Three steps are not simply the reverse of glycolysis:
Pyruvate → PEP
Fructose 1,6 – bisphosphate → fructose 6-phosphate
Glucose 6-phosphate → glucose
10
Q
Pentose Phosphate Pathway
A
Alternative pathway for glucose metabolism
G6P is not broken down to produce ATP
Pathway is primarily anabolic, not catabolic
Occurs in cytoplasm, especially in liver and adrenal cortex
11
Q
Pentose Phosphate Pathway 2
A
Cells do this pathway for two main reasons:
- To generate NADPH
- NADPH differs from NADH by one phosphate group
- NADPH acts as a reducing agent
- NADPH needed as cofactor in synthesis of nucleic acids and fatty acids
- To synthesis phase to produce five-carbon (pentose) sugars
* Ribose and deoxyribose used for synthesis of nucleic acids
12
Q
Protein Metabolism
A
Proteins can hydrolyzed into amino acids and then deaminated
Deamination = amino group removal
Deaminated amino acids can feed into glycolysis as pyruvate
Deaminated amino acids can feed acetyl CoA formation
Deaminated amino acids can feed into TCA as α-ketoglutarate or oxaloacetate
Amino groups from amino acids are incorporated into urea for excretion
13
Q
Deamination means=
A
Deamination = amino group removal
14
Q
Lipids
A
Lipids = a non-polymer class of macromolecule
Examples include fatty acids, mono-, di-, and triacylglyerols (triglycerides)
Triglycerides can be metabolized into glycerol and fatty acids
Glycerol enters glycolysis
β-oxidation breaks fatty acids into 2C pieces, then converted to acetyl CoA → TCA
Other examples of lipids: sterols and sterol esters (e.g., cholesterol); waxes; tocopherols (Vitamin E)
15
Q
Fatty acid catabolism
A
Fatty acids are prepared for beta-oxidation in the mitochondrial matrix
In order to enter the matrix, most fatty acids require the carnitine shuttle
16
Q
Carnitine shuttle
A
The carnitine shuttle consists of three steps:
- A fatty acid (acyl-CoA) is transferred to carnitine on outer mitochondrial membrane
- The acylcarnitine is shuttled into the matrix
- The acylcarnitine is re-converted to the fatty acid (acyl-CoA) on inner membrane
17
Q
Beta-oxidation 1
A
Beta-oxidation = breakdown of fatty acids
- we get fats in our diet in lots of different forms, break big chunks of fat into smaller chunks of fat, chemically process them in digestion chapter
- we break down our lipids get fatty acids, triglyceride single glyercol 3 fatty acids chains, so we have these fatty acids and what we want to do is break them down and this process beta oxidation is how we harvest energy from fatty acids just like the whole pathway glycolysis and krebs, how we harvest energy from sugars* so beta oxidation takes place in mitochondira matrix, first issue of getting molecules into the mitochondrial matrix*
** beta odication puts carbonyl group on beta carbon, that is the same thing as 3-hydroxyacly-CoA, so beta-hydroxy aclycoa and 3-hydroxylacl-coa are the same thign!
18
Q
Beta-oxidation 2
A
Beta-oxidation of saturated, even-chain fatty acids (as acyl-CoA’s) proceeds in 4 steps:
- Dehydrogenation by acyl-CoA dehydrogenase
- Yield: 1 FADH2
- Different isoforms of enzyme have different affinities for fatty acids of different lengths
- Hydration by enoyl-coA hydratase
- Dehydrogenation by beta-hydroxyacyl-CoA dehydrogenase
• Yield: 1 NADH
- Cleavage by acyl-CoA acetyltransferase (also called 3-ketoacyl-CoA thiolase)
- Yield: 1 acetyl-CoA and a fatty acid that is shorter by two carbons
- Acetyl-CoA can then enter the Krebs cycle
19
Q
Odd Chain fatty acids
A
Odd-chain fatty acids are broken down to acetyl-CoA molecules and propionyl-CoA
- Propionyl-CoA is metabolized to succinyl-CoA
- Succinyl-CoA then directly enters the Krebs cycle
- Odd-chain fatty acids are rare in nature
- (if given choice of odd versus even, then you want odd!)
20
Q
Ketone Bodies
A
An alternate energy source
Can be especially important for the brain
Produced under conditions of low caloric intake or carbohydrate restriction
Produced in the liver, in the mitochondria
Produced from acetyl coA
Excess acetyl coA cannot be used directly in Krebs because there’s not enough oxaloacetate to react with it
High levels of circulating ketone bodies make blood more acidic
Ketone bodies enter the Krebs cycle as acetyl-CoA
21
Q
Where are ketone bodies produced?
A
Produced in the liver, in the mitochondria
Produced from acetyl coA
Excess acetyl coA cannot be used directly in Krebs because there’s not enough oxaloacetate to react with it
ketone bodies are used directly by the brain. if really really in a pinch brain has a way to use ketone bodies, prefers glucose but it can use ketone bodies plan B. CANNOT use fatty acids*** so have to have fatty acids broken down into acetyl-coa, aceyl-co gets turned into ketone bodies and that in turns supplies hte brain
Why does the body turn acetyl-CoA into ketone bodies when glucose-starved?
Acetyl CoA can’t be circulated for two reasons: it’s a high energy compound and it’s labile. So it’s not a stable form for circulation to tissues. Also acetyl coA cannot cross cell membrane.
Ketone bodies are an alternate fuel source. More importantly, they are water soluble analogs of fatty acids. This is important since, during starvation there is fat breakdown and excess fatty acids circulate in blood. However, fatty acids cannot be used by brain as fuel since, they cannot cross the blood brain barrier. Liver by producing ketone bodies helps brain cells during starvation.
Also, these ketone bodies, as such, can be used by other tissues as well. There by other tissues refrain from using glucose. Hence, ketone bodies have a glucose-sparing effect. This glucose will be available for tissues like brain and red cells for use.
22
Q
ketoacidosis
A
Extreme form → ketoacidosis (also called ketosis)
Seen in uncontrolled diabetes
Identifiable as the smell of acetone on the breath
23
Q
three kinds of ketones bodies are:
A
acetoacetate, beta-hydroxybutyrate, and acetone
= made from acetyl coa, issue say someone eats a very high fat diet, ton of acetyl coa waiting to get into krebs cycle, but not a lot of acetyl coa can enter krebs cycle immediately, each acetyl coa needs an oxoloactate! So oxoloactate is limiting, so only so much acetyl coa waiting in line to enter krebs cycle, huge traffic jam and then coenzyme A, big molecule not good to have a lot of that soaked up acetyl coa sitting there twiddling thumbs to get into krebs cycle, so from that body makes ketone bodies instead*
24
Q
acetone
A
25
acetoacetate
26
beta-hydroxybutyrate
27
Fatty acid biosynthesis
Fatty acid biosynthesis is a non-template phenomenon
Carbohydrate synthesis is also non-template
By contrast, RNA and DNA synthesis and protein translation depend on templates
Non-template synthesis depends on several variables:
* Expression levels of relevant enzymes
* Availability of substrates
* Localization of enzymes
28
Biosynthetic pathways 1
Straight-chain fats can be built up using acetyl-CoA as a precursor
Process occurs in the cytosol
Acetyl-CoA can come from pyruvate
Acetyl-CoA is converted to malonyl-CoA
Enzyme is acetyl-CoA carboxylase
Reaction requires ATP and CO2
Malonyl-CoA is spontaneously decarboxylated
This drives condensation with the elongating fatty acid chain
29
Biosynthetic pathways 2
Condensation reactions are catalyzed by fatty acid synthase (multi-enzyme complex)- reaction in which a water is removed, very general term but if put together 2 amino acids and make a peptide bond you are kicking out water molecule\* in some bio classes people refer to it as dehydration synhtease, a lot of examples make a polymer, put two things togehter and kicking out a water\* JUST TAKING OUT A WATER MOLECULE\* goes with building things up, can build up an individual fatty acid as well\*
Elongation results in the 16-carbon FA, palmitate
Pathway uses NADPH, converting it to NADP+
NADPH is mainly produced by pentose phosphate pathway
Further elongation can be achieved by enzymes on the smooth ER
Synthesis of lipids that are essential in structural and signaling roles in the cells and tissues may be accomplished through pathways involving phosphatidic acid
it requires NADPH becuase enzyme is requiring NADPH\* so particular nezyme that does this job evolved to require NADPH as opposed to some other energy source\*
30
Within a eukaryotic cell, the β-oxidation of fatty acids takes place in:
A.the cytosol.
B.the rough endoplasmic reticulum.
C.the mitochondria.
D.the ribosomes.
C.
the mitochondria.
β-oxidation is the process by which fatty acids are broken down two carbons at a time to produce acetyl-CoA. This process is carried out within the mitochondria.
31
The first step of fatty acid synthesis is depicted below. In this process, an activated acetyl-CoA molecule reacts with a unit of malonyl-CoA to form an intermediate product.
Which sequence of reaction types, if catalyzed by appropriate enzymes, could convert this intermediate into the corresponding fatty acid product?
A.Reduction → reduction → hydration
B.Reduction → dehydration → oxidation
C.Reduction → dehydration → reduction
D.Reduction → hydration → double dehydration
C.
Reduction → dehydration → reduction
This intermediate must first be reduced at the carbonyl farthest from the CoA substituent, producing a hydroxyl group. The resulting species will then be dehydrated, forming a double bond, which will finally be reduced in the last step. This is the exact opposite of the process by which fatty acids are oxidized.
32
In which of the following locations can ketolysis NOT occur?
A.
The brain
B.
The liver
C.
Skeletal muscle
D.
Cardiac muscle
A.
The brain
Ketolysis can occur in the brain in situations of low blood glucose.
B.
The liver
**Ketolysis, or the breakdown of ketone bodies, is a metabolic process that can provide energy. The liver lacks a particular enzyme required for this process.**
C.
Skeletal muscle
Ketolysis can occur in skeletal muscle in situations of high activity and/or low blood glucose.
D.
Cardiac muscle
Ketolysis can occur in cardiac muscle in situations of ischemia and/or low blood glucose.
33
In gluconeogenesis..... fact about PEP=
for PEP Alanine can be converted to pyruvate in the liver, then fed directly into the pathway.
34
Which phase of the pentose phosphate pathway would be most affected if this enzyme were to become nonfunctional?
A.
Oxidative
B.
Initiation
C.
Non-oxidative
D.
Termination
The protein structure for transketolase is shown below, along with the molecular structure of its cofactor, thiamine pyrophosphate......
35
Question 14- QBank 11-25
Which of the following is FALSE about ATP and its hydrolysis?
A.
The ΔG for ATP hydrolysis is nearly equal to the ΔG for ADP hydrolysis.
B.
Two rounds of ATP hydrolysis yield AMP.
C.
The ΔG for ATP hydrolysis is pH-dependent.
D.
ATP contains two high-energy phosphate bonds.
A.
The ΔG for ATP hydrolysis is nearly equal to the ΔG for ADP hydrolysis.
Both phosphate bonds are very high energy bonds, and release a similar amount of energy when broken.
B.
Two rounds of ATP hydrolysis yield AMP- Two rounds of hydrolysis, with each round removing one phosphate group, would result in AMP, with one remaining phosphate group attached.
**C.**
**The ΔG for ATP hydrolysis is pH-dependent- CORRECT**
**∆G is not affected by pH. The remaining choices are accurate – one high-energy bond can be hydrolyzed to yield ADP, and the second can be hydrolyzed to form AMP. Interestingly, the ∆G value for ATP hydrolysis is almost identical to that for ADP hydrolysis, with both reactions being highly exergonic (negative ∆G).**
D.
ATP contains two high-energy phosphate bonds.
A high-energy phosphate bond is formed when one phosphate binds to another phosphate group. There are two such bonds in the structure of ATP, with the innermost phosphate bound to a carbon atom on the sugar.
36
Carnitine shuttle 2
37
Fatty acid sizes
short/ medium fatty acids Chain
2-12 carbons
38
Long Chain fatty acids
14-20 Carbons
39
Very long chain fatty acids
\> 20 carbons
\*\*How to remember\*= compare # of carbons to age in school, how long do you have to study per age in school\> short amount of time, long amount of time etc.
Short and medium chain between 2 to 12 years old= elementary study a short/medium amount of time not that difficult. So what age you are in school and how long you have to study!
14-20 high school/ college= have to study for a long amount of time, undergraduate school, biology etc to get to med school
Very long chain great than 20- medical school study for a VERY long amount of time\*\*\*
40
Gluconeogenesis 2
1. happens in liver
2. what we would do if haven't eaten in a while, mostly but not completely opposite of glycolysis, three spots where gluconeogenesis differs from glycolysis and why those spots are signficiant
41
Pentose Phosphate Pathway 3
- sugar processing pathway, remember how we talked about glucose goes into cell, phosphorlated to G6P another thing that can happen with G6P can take this and make 5 carbon sugars so starting with G6Phosphate
reasons we do it= 1. to make 5 carbon sugars, specifically this is the pathway you make deoxynucribose and ribose when need to synthesize more nucleotides and 2. other is to produce NADPH\* where we need NADPH is when we are trying to synthesis fatty acids
so the most important thing to understand about pentose pathway is WHY= 1. If cell needs to synthesize more ribose or deoxyribose there is a lot of recycling of ribosme, recycling of nucelotides, in situation where clel really doing a lot of replication or transcription and needed to crank it up a lot this pathway becomes necessary\*\* NEEDS 5 carbon sugars for nuceltoides for DNA or RNA\* other thing want ot notice here is that step 1 and step 2 of this pathway produce a molecule called NADPH\*
Reason 2 = NADP+ is reduced to NADPH in each of these spots, NADP+ is a lot like NAD+ just an extra phosphate group; so can think of it as having a very similar role\* something needs to be reduced NADP+ gets reduced so that carbon skeleton in pathway can be oxidized, so much of that in metabolism, becuase oxidation and redcution reactions have to happen as pair, if one thing is beign oxidized who can go in and be reduced, here nadp+ is beign reduced\*\* significant its NADP+ not NAD+ B/C when cell needs ot synthesize fatty acids, **build up fatty acids it MUST HAVE NADPH, it for some reason pathway that we need ot build fatty acids requires NADPH\*\*** specifically needs this, so sometimes cells will run the pentose phosphate pathway in order to maek NADPH really bcause what they need to do is synthesize fatty acids\*
42
Beta- oxidation 3 (how the mechanisms work)
- The top molecule on fatty acid beta oxidation page- not technically a carboxylic acid, hydrocarbon chain going on left side of molecule, S-CoA, technically a fatty acyl coA, that is the starting material for break down, **so if have an actual fatty acid from something you have eaten have to turn it into a fatty acyl coa\*** then have to use this big complex of proteins and all kinds of fancy footwork to get the fatty acyl coa into the mitochdornia matrix, so transport issues!
- The name to know for that don’t think have to know all the details, **but the process is called the Carnitine shuttle\*** and any enzyme you come across that is a carinitine acyl transferases or anything with transferases in it in this context **means it is involved in bringing fatty acyl coa into mitonchondria matrix so it can be very chopped up for energy\***
43
Beta- oxidation 4 (how mechanism works cnt.)
So once inside cell in mitochondira matrix, probably in much bigger form something we ATE went to blood stream, digeative tract mitochondria of cell… so now ready for real metabolic pathway to take plce, all the other stuff just alluded to quickly will fill in when talk about digestion\* how do these moelcuels get ot cells from stuff that we eat, how does it go from mouth all the way to cell of body, form is changing but what we wnt to talk about now metabolism part of it
- what happens when have fatty acyl-coa in mitochondria\*
1. so the first reaction, involves creating a double bond between the alpha and the beta carbons, so to review that nomenclature, C=0 has c to its left, one away, so that is refered to as alpha carbon, one more over is the beta carbon--\>FAD gets reduced to FADH2 no surprise that involves a dehydrogenase\*
- As FAD is reduced something else needs to be oxidized\* that represents an oxidation\* with carbon skeleton, FADH2 is reduced\*
3. Add water across double bond, OH on beta carbon, then another oxidation of C skeleton, OH turns into ketone group, and while the carbon skeleton is oxidized, NAD+ is reduced to NADH, and that is the other dehydrogenase step\*
44
Beta-oxidation 5 (how it works cnt.)
4. Then we have a substution reaction that happens ; yellow arrows, CoASH, nuc lone pair on sulfur, it is attacking the carbon, electrons go up then go down and the structure boxed in orange is the leaving group!
That is acetyl coa!
Net result of these 4 steps is to split off an acetyl coa from the fatty acid chain\* not an accident that most fatty acids in our bodies have an even number of carbons, because we build them up and break them down two carbons at a time, typical scenario that maybe the molecule at the top of this page had a total of 14 carbons or 16 or 18 carbons, and then after we go through all the steps all the way down this page, split off an acetyl coa have a leftover molecule that has 12 carbons. Then we go back around to the top and the 12 carbon moelcule goes through this algorithm we split off another acetyl coa, then we have a 10 carbon remained fatty acyl coa and then we do it again and again, until we have broken down our fatty acid unit, a whole bunch of aceyl coa
45
Beta- oxidation 6 (how it works cnt.)
So you get really a lot of fadh2 and nadh frm this process
Imagine 14 carbon fatty acyl coa =7 nadhs make 7 rounds, if 14 chopping up to 14 c units gives us 7 acetyl coa molecules, 6 rounds\* of beta oxidation will always be one fewer cut mark, each red cut mark represents a round fo beta oxidation! Everytime we go thrugh a round fo beta oxidation, get an fadh2 and an nadh, in this process get 6 nadhs and 6 fadh2\*
ON TOP OF everything we get from acetyl coas, also made 7 acetyl coas, and each one of those acetyl coas in theory may be able to enter the krebs cycle!
**Overall very high yield per gram of fatty acid you can make more atp then you can per gram of glucose\*\*- every round of beta oxidation get nadh and fadh2 adds, take that and go into krebs so technically making a LOT MORE- fat stores are our ultimate energy reserves, glucose fat is our real energy store\* it is a very efficient way to store energy voer longer periods of time\***
**overall very high yield per gram of fatty acid can make you more atp then you can per gram of glucose know that fact**
Acetyl coa can enter krebs cycle, **CANNOT ENTER GLUCONEOGENESIS can't take fatty acids break down to aceyl coa then go backwards to pryvuate** then pryuvate ot go up through gluconeogenesis to glcusoe, that doesn’t happen in mammals, very important because it means that we can’t get glucose from fats\*
46
Lipid synthesis
If think about fatty acids being built up, they are built up two carbons at a time by an enzyme called fatty acid synthase, malonyl coA two carbons of malonyl coA that get loaded onto fatty acid chain, keep cycling around with fatty acid synthase adding two more carbons, two more carbons, want to make a 14 c fatty acid
**Really really important to understand two carbons being added on are not coming from acetyl coa coming from slightly bigger molecule called malonyl CoA,** meaningful when two carbons added onto growing fatty acid chain, carboxyl group on left gets driven off as Co2 that process of releasing co2 provides enormous forward drive for this reaction
Entropy point of view producing a gas and driving it off, why adaptive for malonyl coa to be source of these two carbons rather than acetyl coa, this whole process requires nadph\* so remember nadph can be generated through PPP and then you need it for lipid synthease, this is where it is needed for this reaction\*
47
Ketone bodies 2
when blood sugar low the brain can use ketone bodies to power itself, all fat diet has a really bad side which is that ketone bodies are acidic so two are carboxylic acid\* alpha carbon, so if you overload on ketone bodies you lower your pH making it acidic
come about in different ways too many ketone bodies=short term benefit for your brain, but if blood pH falls too much you get ketoacidosis, can definitely happen ppl subscribing to extreme keto diets, depending how strict they are
the people this is really a big danger for are ppl with DIABETES\*
1. If someone has diabetes type 1**= biggest issue, scenario where have a child who cannot produce insulin, so that child needs to take insulin,** lets imagine that a scenario of untreated diabetes blood sugar is soaring after a meal and there is no insulin available to bring glucose into cells from blood, blood sugar levels sky high but from the point of the view of cells, cells think they are starving, can't get glucose beucase no insulin
2. What that means is that the cells start sending all kinds of signals out to mobilize other reserves to mobilize other macro moelcules, wht ends up happening ppl with diabetes in that scenario they are doing beta oxidation like crazy, they will have a tone of aceylcoA and make a ton of ketone bodies to provide energy for the brain, and that has value, the brain needs an energy supply there is no glucose available, or glucose that can get in there so brain is using ketone bodies, but the kicker is that the blood is getting more and more acidic, so when ppl are going into ketoacidosis that can be a life threatening situation
1. One of the most intense and compelling issues around access to medication is access to insulin, all these stories of rationing insulin becuase they cannot afford it they can very easily die from ketoacidosis becusae of mechanism talking about
48
Odd Chain fatty acid synthesis 2
Not really relevant so much in real life context thought experiment that comes up a lot in biochem classes, the question is that if you are only t**o eat fats all fat diet it is better to have some odd chain fatty acids then even if only eating fats**
**In beta oxidation process chopping up fatty acids splitting up two carbons and two carbons,** 15 c total get down to end 3 carbon molecule left, instead of last acetyl coa so the 3 carbon molecule you have left is called **propinyl coA**
Propinyl coA through a whole other pathway you don’t need to know about can be converted to **succinyl coa** intermediate in krebs cycle that can be turned into oxolacate, **so that means can supply one more oxolaoacateate so can take one more acetyl coa into krebs cycle so making one fewer ketone body!**
49
Protein metabolism 2
For proteins to break down you first hydrolyze peptide bond --break peptide bond into individual amino acids, then amino acids need to deanimated, which means amino group needs ot be taken off.
Then the rest of the carbon skeleton can be fed into one of the other pathways we have been talking about depending on which amino acid you started with, for some after deanimate it skeleton great goes into glycolsis or gluconeogenesis depending on which way you are running pathway, or may have skeleton manipulate it a bit to turn into alpha-ketoglutamate in krebs cycle etc, so much versatility for amino acids once take off amino group, all these pathways for converting one amino acid into another
SO methodology= hydrolzye peptide bonds, take off amino group and then carbon can go in many directions depending on what we started with\*
1. **Deanimating= taking off amino group, also possible in some cases to if you have an amide, so if you have two amino acids asparagine and glutamine have an amide group on the side chain, can be deamidated\* take off amide group! So can imagine in some mutlipel choice, deaminate versus deamindate; if side chain doesn’t have a ntirgoen in special group, just deaminate, if lysine deaminate side chain, but if have an amide group\* on the side chain like asparagine or glutamine, then do deamindate\* to hydrolyze amide group**
2. Also Atp- gamma phosphate group hydrolzyed off whne go frm ATP to ADP
50
Ex of a steroid
- cholesterol\* and know its chemically found in lipid rafts, lipid enriched parts of
- four fused rings
- various other steroid hromones like estrogen and protesterone, know what characteirzes steroid picture **4 fused rings, specifically what cholesterol is**
51
1. Which of the following does NOT occur in the mitochondria?
a. oxidative phosphorylation.
b. pyruvate decarboxylation
c. The Krebs cycle
d. Formation of water from the reduction of oxygen
e. Fermentation
e. Fermentation occurs in cytosol, can still have mitochdonria with no O2
glycolsis will create **pyruvate** which is transported to mitochondria maxtrix to be decarboxylated which then goes to fermentation
52
3. Consider a pyruvate molecule during aerobic respiration. After this molecule enters the mitochondrial matrix, its full metabolism will generate how many ATP?
15
means after all is said and done will generate 15 atp after ETC
53
4. Inhibition of the enzyme phosphofructokinase (PFK):
a. occurs in the mitochondria
b. occurs in the intermembrane space of the mito.
c. would occur in the presence of high citrate
d. would occur as a result of high NAD
e. means that the organism is operating under anaerobic conditions
C. would occur in presence of high citrate\*\*\*
occurs in cytoplasm with glycolysis
way of letting glycolysis know what is happening downstream because ctirate is created in one of the steps of the Krebs cycle. High citrate would create a traffic jam in the krebs cycle so need to pause glycolysis and hit puase\*
54
6. At the beginning of the electron transport Chain:
a. NADH is formed
b. electrons have more potential energy than they do further along the chain
c. FADH2 and NADH compete to bind with the same protein
d. oxygen is reduced, forming water
**b. electrons have more potential energy than they do further along the chain\*\*\***
d- no happens at the end and c. no they bind with different proteins\*
B is right because NADH drops off very high energy electrons to the first structure I. As electrons go down ETC they give up electron potential energy which is then used to pump protons at complex I, III and IV\*
NADH drop-off very high energy electrons to Complex I.
e move down falling down a staircase or going step by step down a staircase and the energy potential that they are losing going electrically downhill is being harnessed to pump the protons, where energy comes from to push H+s against their gradient into the inner membrane space\*
55
7. Cyanide is a highly toxic inhibitor of aerobic respiration. It functions by binding cytochrome a3. (complex C\* like c for cyanide). This target is located within:
a. the cytoplasm
b. the outer mitochondrial matrix
c. the inner mitochondrial matrix
d. the mitochondrial matrix
c. the inner mitochondrial matrix\*\*
56
9. one significant feature of fermentation in human muscle cells is that it:
a. releases Co2
b. regenreates NAD+
c. yields alcohol as an end product
d. produces ATP by oxidative phosphorlyation
**b. regenerates NAD+\*\*\*\***
does not release CO2 because bacteria and humans do not release co2 through fermentation\*\* unlike with others like yeast\*
ethanol end product in yeast
under aerobic conditions when there isnt enough oxygen present we do glycolysis\* we cannot do more than that, so under anaerobic conditions get all atp from glycolysis\* pretty low yield than if had O and id whole aerobics conditions to the end with oxidative phosphorylation, but couldn’t keep doing lgylocisys unless had some way of regernatign **NAD\*\*\*\* with fermentation\* All fermentation runs produce NAD+ as a product, that is important b/c glycolysis uses NAD+ and turns it into NADH, under aerobic conditions NADH is oxidized in complex I\***
GLYCOLYSIS= NAD+ is converted to NADH\*\*\*
Under aerobic conditions: NADH—\> NAD+ at complex I of the ETC\* under anaerobic conditions NADH goes back to NAD+ through fermentation\*\* but the point iS YOU NEED NAD+ FOR GLYCOLYSIS\*\*\*\* if no way to regenerate NADH do not get ATP from glycolsis anymore\*
only version that occurs in yeast that releases CO2
57
10. Reactants participating in pyruvate decarboxylation include all of the following except:
a. CO2
b. Coenzyme A
c. NAD+
d. Pyruvate
a. CO2
that is a product not a reactant\*
58
13. Consider aerobic vs. anaerobic respiration performed by the same eukaryote.. Anaerobic respiration will yield roughly:
5% as much ATP\*\*
Anaerobic respiration is way less efficient.
Under anerobic conditions 2 ATP are made in glycolsis
under aerobic respiration conditions: 36-38 ATP are made, with glycolysis, purivate decarboxylation, Krebs and ETC where evyerthing that can be converted to ATP is\*\*\*
how you do this math is 2/38 is around .05
.05 X 100= 5%\*\*
59
14. An example of oxidative phosphorlyation would be:
a. conversion of GTP to ATP
b. production of ATP during glycolysis
c. production of GTP during the Krebs cycle
d. production of ATP using energy stored in FADH2 in ETC
e. the converstion of NAD+ to NADH by the Krebs cycle
d. the production of ATP using energy stored in FADH2 in ETC
All other examples are substrate level phosphorylation\*
60
27. The process of glycogenolysis:
a. occurs in the liver
b. is inhibited by epinephrine
c. uses many of the same enzymes as glycolysis
d. occurs mainly under anaerobic conditions
a. occurs in the liver
everything with glycogen is in the liver! stored as glycogen, when we need more break down glycogen in liver to get glucose
- would not be inhibited by epinephrine because would result in higher blood sugar and need lots of glucose to raise blood sugar, so break down NOT inhibited
61
29. A proton-uncoupler like dinitrophenol does which of the following?
a. Prevents the oxidation of NADH at the bginning of the electron transport chain
b. inhibits the release of heat from the electron transport chain
c. makes the intermembrane space more acidic
d. Reduces the amount of ATP produced per glucose
d. Reduces the amount of ATP produced per glucose\*
REMEMBER a proton uncoupler pokes holes in membrane, creating channels that H+ can go through\* and so basically that allows the protons to slide back down into the matrix so a proton uncoupler allows H+ to get back to the matrix without going through ATP synthase\* big deal becuase then do not get same atp yield with another way back through matrix
c- no makes it less acidic becuase allowing H+ to leave. Cyanide acts on Cytochrome C, but dinitrphenol works along the membrane all the way down making holes it allows the membrane to become veyr leaky\*
62
30. The enzyme hexokinase:
**has a high affinity for glucose and a low vmax\*\***
hexokinase- in lots of cells, higher affinity, lower km
glucokinase- in liver, lower affinity for glucose HIGHER KM, blood from small intestine flows first through liver hepatic portal vein liver gets first crack at glucose, if a lot of glucose you want liver to take some and store as glycogen but do not want liver to be greedy and soak up so much glucose that there isn't enough available for other organs that come later by having an enzyme with low affinity for glucose this means liver will only hold onto glucose if excess so much glucose present, if not a lot of glucose liver will not soak it up and deprive other organs\*\*
63
31. The enzyme glucokinase:
a. has a higher Km for glucose than hexokinase
b. is not found in the liver
c. has a lower Vmax than hexokinase
d. phosphorylates glucose in skeletal muscle, thereby trapping it inside of cell
a. has a higher Km for glucose than hexokinase
high KM means lower affinity, and a high vmax\* all true
glucokinase is found in the liver\* hexokinase in all other cells
64
34. As we know, gluconeogenesis is not simply the reverse of glycolysis. At three points it relies on different enzymes. This is important because otherwise:
a. gluconeo. would be too slow to meet physiological demand
b. the overall Keq for gluconeogenesis would be greater than 1
c. the overall delta G for glucogeneosis would be positive
d. glycogen synthesis would be inadequate to meet the cell's needs.
c. the overall delta G for glucogeneosis would be positive\*\*\*
glycolsyis overlal delta G is negative! in downward direction
if gluconeogenesis just reverse would have a delta G + and that is not good would be different expending energy changing it up so glucogneogenesis has a delta G negative so can also be sponatenous and favorable
this is how it becomes favorable and is obviously very important\*
65
38. The enzyme glucose 6- phosphatase catalyzes the hydrolysis of glucose 6-phosphate to glucose. Which of the following is true statement about that reaction?
a. it involves the hydrolysis of a phosphoester bond
b. it involves positive free energy change
c. it occurs in muscle cells
d. it occurs early in the process of glycogenesis
**a. it involves the hydrolysis of a phosphoester bond- TRUE this bond links two sugars of a nucelic acid\***
b. it involves positive free energy change- no it is not positive it is negative delta G free energy change
c. it occurs in muscle cells- no occurs mostly in the liver
d. it occurs early in the process of glycogenesis- no occurs at the end\*\*
A phosphodiester bond occurs when exactly two of the hydroxyl groups in phosphoric acid react with hydroxyl groups on other molecules to form two ester bonds. The "bond" involves this linkage C-O-PO2−-O-C. Discussion of phosphodiesters is dominated by their prevalence in DNA and RNA, but phosphodiesters occur in other biomolecules, e.g. acyl carrier proteins.
Phosphodiester bonds make up the backbones of DNA and RNA. The phosphate is attached to the 5' carbon. The 3' carbon of one sugar is bonded to the 5' phosphate of the adjacent sugar.Specifically, the phosphodiester bond links the 3' carbon atom of one sugar molecule and the 5' carbon atom of another (hence the name, 3', 5' phosphodiester linkage).
66
39. Which of the following is a true statement involving uncontrolled type 1 diabetes?
a. hexokinase is unable to properly phosphorylate glucose
b. blood pH increases
c. pyruvate oxidation increases
d. Ketone bodies provide fuel for the brain
**d. Ketone bodies provide fuel for the brain- good thing is that they provide food for the brain, bad thing is that too many make blood acidic and can have ketoacidosis**
a. is wrong because no insulin, liver doesn't recognize glucose cannot get it into liver still in blood
b. is wrong b.c blood pH decreases only b/c of ketone bodies, make blood more acidic
67
42. If an individual were to eat only fats and no carbohydrates, it would be healthier to eat more fatty acids with:
an odd number of carbons b/c propinyl-CoA can be converted to one of hte intermediates in the Krebs cycle
SO NOT an even number of carbons\*
68
41. Beta- oxidation of a saturatd fatty acid containing 13 carbons directly produces:
5 acetyl-Coa and 1 propionyl-Coa
10 c for 5 acetyl coa
extra 3 left over go to 1 propionyl-Coa
69
43. Which of the following CANNOT be used directly for gluconeogenesis?
a. Acetyl-Coa
b. oxaloacetate
c. glycercol
d. some amino acids
answer is A. acetyl-Coa
b c and d are yes, oxaloacetate is part of the pathway can be added directly in\*
- if break down a lot of fatty acids and have a lot of acetyl coa, cannot make glucose from acetyl coa\*\*\* cannot go backwards. so that route is blocked off in that direction\*
70
44. NADH can reduce a carbonyl to an alcohol by donating:
a Hydride
teh difference btw a hydride, neutral H atom, proton and electrons is that a proton is H+ is missing an electron so has a positive charge
a Hydride is H- with 2 electrons, extra electron!!! so not netural H atom!
71
49. If a rat liver cell is carrying out large amounts of gluconeogenesis using oxaloacetate as a starting material:
a. oxaloacetate would be less available for the Krebs cycle and the Krebs cycle would be inhibited
b. acetyl-Coa would be less available for the Krebs cycle and the Krebs cycle would be inhibited
c. the cell would produce more oxaloacetate by increasing the net rate of Krebs cycle reactions
d. the cell could replenish this oxaloacetate by increasing the rate of beta-oxidation of fatty acids
A. is correct oxaloacetate would be less available and krebs cycle would be inhibited, c wron gbecuase not increase net rate
**Krebs cycle has like a fixed amount of oxaloacatete\* which is the limiting reagent of this reaction that starts off krebs cycle,** acetyl CoA keeps coming in, pyruvate turns into acetyl COa can be a lot of acetyl coA or not depending on how recently you have eaten, or oxaloactate fixed and finale amount gets used to make citrate\* then say we are talking about 1 gets used and regenerated\* but no NET GAIN in oxoloactate in krebs cycle, therefore if you divert it\*\* into gluconeogenesis which is actually a pathway that consumes oxoloactate and uses it up, then there is less available for krebs cycle so you slow down the krebs cycle
72
50. Which of the following would favor gluconeogenesis over glycolysis?
a. The presence of insulin
b. a fed state
c. an increase in citrate
d. an increase in glucose
a. The presence of insulin
b. a fed state
**c. an increase in citrate- CORRECT**
d. an increase in glucose
a and b would promote glycogen synhtesis\*\* whereas c inhibites glycolysis
73
52. Given your knowledge of hte ETC, the half reaction with positive value of E' (meaning the one with teh most favorable reduction potential) should involve which of the following as a reactant?
a. NAD+
b. Ubiquinone
c. Cytochrome c
d. Oxygen
answer is D oxygen
b/c at the end of the chain most favorable! we said electrons are moving downhill as they go down electron transport chain, **another way of saying that is that each reaction is more favorable then the one that came before it\* another way of saying that is the e value of redox reactions\*\*\*** each redox reaction has to be more favorable which means a more positive E value than the reaction right before it\* Oxygen is at the end, in order for electrons to keep moving each reaction has to be better than the one before it otherwise they would be like no I am here\* favorable for electrons to keep going, in order for it to happen and get all the way there it has to be the most favorable reaction\* **most favorable in gen chem terms means most positive value of E\*\*\***
74
59. During the Krebs cycle, succinate is:
a. oxidized to fumarate
b. reduced to fumarate
c. oxidized to succinyl CoA
d. reduced to succinyl CoA
a. oxidized to fumarate
dehydrogenase is an enzyme in redox reactions!!
enzyme here is succinate dehydrogenase
FAD+ to FADH2 redcued because connected to more H MRE H ADDING ON IS A REDUCTION\*
if FAD is reduced succinate has to be oxidized if just look at strutures, fever bonds to H, more bonds to O so oxidation!
from -OoC-Ch2-Ch2-Coo- to--\> -OOC-CH=CH-Coo-
less bonds to H!
75
Glycogenesis 3
glucose comes into cell, trapped just like before as G6P, but now its converted to glucose 1 phosphate, then glucose 1 phosphate converted into a form called UTP glucose\*\*
**molecule UTP is like atp but with uracil not adenine its Uracil Triphospahte\*\* and basically it gets added on to glucose as a way of priming glucose to be added onto glycogen chain\* so UTP glucose loads the glucose onto the glycogen, and then the enzymes glycogen synthase\*** is responsible for actually adding that glucose to chain, however many glucose units it was is now N+ 1 glucose; glucose sub n--\> glucose n+1 units
idea long chain of glucoses, long chain like if 5 then after this reaction have 6 then again its 7 adding glucose one at a time\*
1. Then the astrix at the bottom of the page, alpha1,4 glysodiic linakges created by this pathway, very very important fact to have\* glycogen also has a lot of branches alpha-1,6, glycosidic linkages, those branches exist but don’t have to memorize any of the biochemsitry for branching enzymes\*\*
76
Glycogenoylsis 3
The break down of glycogen follows most of the same stuff in reverse, first part is just slightly different glycogen phosphorylase enzyme splits off a glucose and it comes off as a glucose 1 phosphate, gets phosphorylated as comes off of glycogen
Go through pathway then liver can release glucose into blood stream **which is the point of breaking down glycogen is to raise blood sugar\***
1. **Lefthand side of page is facilitated by insulin\* making glycogen is when you are in the fed state, with insulin**
2. **Breaking down glycogen is when haven’t eaten for a while and hormone directing things would be glucagon\***
77
Gluconeogenesis Steps 2
The big thing you can't use for glucogeneosis is **acetyl-co a or immediate breakdown** **products of that**, but you can use carbs, oxaoloacate some amino acids if take the amino group off then can use them\* definitely don’t need to memorize which amino acids have right carbon skeleton to feed into this too much detail, but just know some amino acids if deaminate them take off amino group can do this to
Key beginning difference besides cannot start with acetyl-Coa= start with pyruvate to phosphoenolpyruvate step, very very negative delta G reaction highly exothermic, energetically really really expensive to climb back up hill to phosphoenolpyruvate, so cells have evolved to do it in two steps, first made into oxaloacetate then oxaloacetate then made into phosphenolpyruvate\*
1. **When ppl talk about gluconeogenesis being energetically expensive pointing to this, need 2 atps for that first step and 2 gtps for second step, that is a BIG energy investment\***
78
Gluconeogenesis Steps 3
Everything is the same until we get to fructose 1,6-bisphosphate if we think about the reaction that created fructose 1,6, bisphosphate in glycolsis reaction that utilized atp, used an atp so that means if really to actually run that backwards have to make an ATP so that is totally not our goal, not trying to make atp just spent a whole bunch fo atp, trying to make glucose a different goal, so rather than try to run phosphofructokinase in reverse, the cell hydrolyzes off one of the phosphate groups\*\* and therefore if you look on orange side the enzyme used there fructose1,6-bisphosphatase\* the word **phosphatase\*\* implies hydrolysis removal of phosphate group**, just getting fructose1,6bisphosphate to look like fructose-6-phosphate and not do anything extra\* On image has H20 to Pi
Same issue arises going from glucose-6-phosphate to glucose
Look on glycolsis side hexokinase step, atp used by hexokinase, if working it backwards gluconeogenesis side, all we need to do is get rid of phosphate group don’t need to tangle with atp, just use phosphatase, get rid of phosphate group make glucose and call it a day\*
79
Gluconeogenesis delta G details
What these three points have in common is all of the reactions involved are very ngative delta G\* in the glycolysis direction so they would be hard hills to climb if cell tried to do same pahway in reverse has to go around in some way\*
Other conceptual point if glycolsis has an overall negative delta G meaning spontaneous, something now has to be different otherwise glucogeneosis would have positive delta G if truly the reverse, that is not favorable at all, so other way to think about work arounds in gluconeogenesis they give an overall negative delta G as well with these work arounds why its good!
80
Why do we need NADPH?
get from PPP
## Footnote
Build up fatty acids it MUST HAVE NADPH
For some reason pathway that we need ot build fatty acids requires NADPH\*\* specifically needs this, so sometimes cells will run the pentose phosphate pathway in order to make NADPH really bcause what they need to do is synthesize fatty acids\*
81
Why do we need PPP?
1. If syntehsizing a crazy large amount of dna or rna, 2. if needs to be synthesizing fatty acids, in both those scenarios it would run the pentose phosphate pathway\*; feedback loops related to circumstances of the cell, if cell needs to synthesize DNA and RNA there could be a bunch of reasons why that is true, if cell needs to sythesize fatty acids could be more common in fed state\*
1. Cell would have to be synthesizing fatty acids, because it needs to be building more membrane or something, really depends on what the cells job is at the moment\*
2. Cells makes 5 carbon sugars, specifically ribose and deoxyribose and NADPH for fatty acid synthesis in PPP\*
82
storing fats..
can make blobs of fats that do not need water to dissolve them, nonpolar store houses
why you want glycogen stored not glucose stored
takes more water to solubilize glucose, need H20 all the way around glcyogen requires less water all the way around\*\*\*\* we are always trying to conserve water\*\*
83
why does glucose addition require a primer in the form of glycogen or gltycogenin protein?
glucose alone as a monomer unit is too inert or low energy to be a full participant in that reaction, so there just needs to be something to energize hte whole system a tiny bit\*\*\*
84
condensation rxns vs hydrolysis
lipases break apart bonds by adding a water molecule across bonds, so do this in small intestine\*
proteases break down things through hydrolysis by adding a water molecule BIG PICTURE TERM THEY LOVE TO USE\*\* be aware of all the things that fall under these umbrellas\* hydrolsis anytime add a water to break one of these bonds, condesnation anytime take away a water molecule
85
glycerol forming...
lipases fundamentally adding H20 across double bond to break fatty acids and make glycerol
