Exam 3 new Flashcards
1
Q
What is bioenergetics?
A
Quantitative study of energy transductions in aerobic organisms
The ultimate electron acceptor in the oxidation of carbon is O2, with CO2 as the oxidation product and H2O as the reduction product.
2
Q
What does a more reduced carbon indicate about its oxidation?
A
The more exergonic (energy-releasing) its oxidation will be.
3
Q
What is ΔG’°?
A
Standard free energy change determined at standard conditions (pH 7.0, 1 mM Mg²⁺, 1 M other reactants).
4
Q
What does a negative ΔG’° value indicate about a reaction?
A
The reaction proceeds forward. Keq is greater than 1
5
Q
What does a ΔG’° value of 0 indicate?
A
The reaction is at equilibrium. Keq is1.0
6
Q
What does a positive ΔG’° value indicate about a reaction?
A
The reaction proceeds in reverse. Keq is less than 1.0
7
Q
What units of energy are used in the text?
A
Joules and kilojoules.
4.184 J = 1 cal
4.184 kJ = 1 kcal = 1 Cal
note: 1 Cal (dietary) = 1000 cal (chemical)
8
Q
What is catabolism?
A
The degradative phase of metabolism that releases energy.
9
Q
What is anabolism?
A
The building phase of metabolism that requires energy.
10
Q
What is the role of ATP in metabolism?
A
ATP is the chemical link between catabolism and anabolism; it is the universal energy currency in living organisms.
- energy obtained from catabolism of nutrient molecules is used to make ATP from ADP and Pi
- the exergonic conversion of ATP to ADP and Pi (or to AMP and PPi) is coupled to many endergonic reactions and processes
- Transfer of its phosphoryl group to a water molecule or metabolic intermediates provides the energetic push.
- Mg2+ in the cytosol binds to ATP and ADP
for most enzymatic reactions involving ATP, the true substrate is MgATP2-
11
Q
What is glycolysis?
A
The process by which a molecule of glucose is degraded in a series of enzyme-catalyzed reactions to yield two molecules of pyruvate.
–some free energy is conserved as ATP and NADH
–Glycolysis has two phases: Preparatory and payoff
12
Q
What are the two phases of glycolysis?
A
Preparatory phase and payoff phase.
13
Q
What occurs during the preparatory phase of glycolysis?
A
–2 ATP are consumed (energy invested)
–∆G of the intermediates increases
–hexose carbon chains are converted to glyceraldehyde 3-phosphate (G3P)
14
Q
What is the first step (R1) of the preparatory phase of glycolysis?
A
Glucose is phosphorylated, and the reaction is irreversible under cellular conditions.
- Priming reaction -> invest ATP
- Kinase: transfers gamma- phosphate from ATP to a substrate molecule.
15
Q
What is the second step (R2) of the preparatory phase of glycolysis?
A
The enzyme catalyzes the reversible isomerization of an aldose to a ketose.
Ring opens first
Active-site Glutamate serves first as a general base (B:). Electron withdrawal by adjacent groups makes this proton abstraction from a carbon feasible.
Then same Glu acts as
general acid (BH)
Overall, C-2 instead of C-1 becomes anomeric carbon
Q: What side is favored thermodynamically and
why?
It is not strongly thermodynamically favored on its own. It proceeds forward in cells because F6P is rapidly consumed in the next step
16
Q
What is the function of isomerase in glycolysis?
A
To facilitate the intramolecular rearrangement of an aldose to a ketose in R2 of Preparatory phase.
17
Q
What is the third (R3) of the preparatory phase of glycolysis?
A
Called PFK-1 to distinguish it from PFK-2, which catalyzes the formation of fructose 2,6- bisphosphate from fructose 6- phosphate in a separate pathway
Large negative ΔG’° favors product formation, and reaction is practically irreversible in cell. Compensates for reaction 2 having positive ΔG’°.
Q: Why is this the first committed step of glycolysis? Because after this step, the product is committed to going only through glycolysis
18
Q
What is the fourth (R4) of the preparatory phase of glycolysis?
A
Aldolase catalyzes a fully reversible reaction that converts a 6C compound into two different 3C compounds.
- Note ΔG’° is high (the reaction is unfavorable in the forward direction) — but the reaction still occurs because of cellular concentrations
Ring opens first
G3P released as first product upon cleavage between C-3 and C-4
DHAP released later as second product
Several steps involve general acids/bases in the active site
19
Q
What is the fifth (R5) of the preparatory phase of glycolysis?
A
Only glyceraldehyde 3- phosphate (G3P) is directly degraded in the subsequent “payoff” steps of glycolysis.
So: rapid interconversion between G3P & DHAP.
Preparatory phase is now complete!
20
Q
Some reactions in glycolysis have a positive ΔG’°. So why does glycolysis occur?
A. Positive ΔG’° means the reaction is favorable; thus those reactions proceed readily
B. Those reactions are unfavorable, but they are bypassed so they never have to occur
C. Those reactions are very unfavorable by default, but allosteric regulator molecules always activate the enzymes so the reactions are favorable
D. The biochemical standard free energy change for the reaction (ΔG’°) may be positive, but the actual free energy change under cellular conditions (ΔG) is closer to zero due to the cellular concentrations of products vs. substrates, and thus the reaction may proceed
E. None of the other answers is correct
A
The biochemical standard free energy change for the reaction (ΔG’°) may be positive, but the actual free energy change under cellular conditions (ΔG) is closer to zero due to the cellular concentrations of products vs. substrates, and thus the reaction may proceed
21
Q
Payoff Phase
A
- energy conserved as 4 ATP and 2 NADH
–2 pyruvate
22
Q
What happens during R6 in the payoff phase?
A
The first step in the payoff phase is an oxidation reaction that leads to the formation of a high-energy acyl phosphate. This acyl phosphate has a large negative ΔG’°, making it a high- energy intermediate capable of driving ATP synthesis.
NAD⁺ is reduced to NADH. The cell’s supply of NAD+ would be quickly exhausted if it were not recycled from NADH
Reactive active-site Cys
Covalent intermediate between enzyme and G3P
^ gets oxidized by NAD+, which gets reduced to NADH
Pi attacks and releases product
23
Q
What is the significance of the first ATP generated in glycolysis?
A
It occurs in payoff phase R7, where the high-energy acyl phosphoryl group is transferred to ADP.
24
Q
Fill in the blank: Glycolysis is an almost universal central pathway of __________.
A
Glucose catabolism.
25
What happens during R7 in the payoff phase?
The enzyme transfers the high-energy acyl phosphoryl group to ADP, forming ATP.
The enzyme is named for the reverse direction, as the reaction is reversible.
The large negative ΔG’° pays for the prior reactions thermodynamically.
26
What occurs to NAD⁺ during glycolysis?
It is reduced to NADH.
27
What maintains the supply of NAD⁺ in the cell?
It is recycled from NADH.
28
What happens during R8 in the payoff phase?
The enzyme catalyzes the reversible shift of the phosphoryl group between the C-3 and C-2 of glycerate.
29
What happens during R9 in the payoff phase?
This enolase reaction generates a second high-energy compound (first in step 6), phosphoenolpyruvate,
that will spontaneously release its phosphate.
Release of a molecule of H2O
30
What happens in Reaction 10 of the payoff phase?
2nd ATP generated
The transfer of the phosphoryl group to ADP forms ATP and completes glycolysis.
Formation of Pyruvate
Pyruvate Kinase requires K+ and either Mg2+ or Mn2+
This is another “substrate-level phosphorylation” (like step 7).
The product pyruvate tautomerizes rapidly and nonenzymatically to its preferred keto form (at pH=7)
This tautomerization also drives the reaction forward since it removes the product.
31
What does the enolase reaction in Reaction 9 generate?
Phosphoenolpyruvate, a high-energy compound that will spontaneously release its phosphate.
32
Noteworthy Chemical Transformations of Glycolysis
1. breakdown of the carbon skeleton of glucose to yield pyruvate
1 Glucose (6 C) = 2 pyruvate (3 C)
2. phosphorylation of ADP to ATP by compounds with high phosphoryl group transfer potential, formed during glycolysis
4 ATP produced -2 ATP consumed = net production of 2 ATP
3. transfer of a hydride ion to NAD+, forming NADH
2 NADH
33
What is required for Pyruvate Kinase to function?
K+ and either Mg2+ or Mn2+.
34
Which of the following about glycolysis is TRUE?
A. It is the beginning of the complete reduction of glucose
B. Some of the 10 steps occur spontaneously, whereas others are enzyme- catalyzed
C. It generates two molecules of pyruvate per molecule of glucose
D. The steps with positive ΔG’° are unlikely to occur in cells
E. ADP, ATP, Pi, and glucose are the only required inputs to the pathway
It generates two molecules of pyruvate per molecule of glucose
35
What occurs to pyruvate after its formation in glycolysis?
It tautomerizes rapidly and nonenzymatically to its preferred keto form.
36
Define tautomerization.
A type of isomerization where a molecule rapidly interconverts between structural forms by the movement of a hydrogen atom and a corresponding shift of a double bond.
37
What is the net production of ATP in glycolysis?
2 ATP.
38
What is the overall balance sheet of glycolysis?
Net of 2 ATP, 2 NADH, and 2 pyruvate.
39
What is the standard free-energy change for the complete oxidation of glucose to CO2 and H2O?
-2,840 kJ/mol.
40
How many molecules of pyruvate are generated per molecule of glucose?
Two molecules.
41
True or False: Glycolysis is the beginning of the complete reduction of glucose.
False, it is the beginning of the complete oxidation of glucose.
42
Which substances are required inputs for the glycolytic pathway?
ADP, ATP, Pi, and glucose (NAD+ is also required).
43
What does NAD stand for?
Nicotinamide Adenine Dinucleotide
## Footnote
NAD is a coenzyme central to metabolism.
44
Why is NAD called a dinucleotide?
It consists of two nucleotides joined through their phosphate groups.
45
What are the two forms of NAD?
* NAD+ (oxidized form)
* NADH (reduced form, H for hydrogen)
46
What role does NADH play in metabolism?
Acts as a carrier of electrons and protons during redox reactions.
47
Which enzyme catalyzes the first committed step in glycolysis?
Phosphofructokinase-1
48
Why are all intermediates in glycolysis phosphorylated?
To inhibit transport through GLUT and retain energy for ATP production.
## Footnote
All 9 intermediates are phosphorylated. That is because…:
Glucose is transported into cell via facilitated passive diffusion by a carrier (GLUT). This carrier is reversible. Phosphorylation changes charge and structure of glucose. This inhibits its transport through GLUT and out of cell.
The energy released in the hydrolysis of the phosphodiester bond of ATP is partially retained in the phosphodiester bond of a product/reactant. High- energy intermediates (BPG and PEP) can then transfer phosphate to ADP to make ATP. Serve as essential components in the enzymatic conservation of metabolic energy
Binding energy of phosphate intermediates to enzymes is increased because of phosphate. This helps drive catalysis.
49
What is the function of high-energy intermediates like BPG and PEP in glycolysis?
They can transfer phosphate to ADP to make ATP.
50
What are feeder pathways for glycolysis?
Many carbohydrates (other than glucose) are catabolized through glycolysis
Some are converted to D-glucose or glycolytic intermediates
the most significant are the:
monosaccharides fructose, mannose, and galactose
disaccharides maltose, lactose, trehalose, and sucrose
They are funneled into glycolysis at different points, allowing the cell to harvest energy from a wide range of dietary sugars efficiently
51
How does starch catabolism begin?
catabolism (digestion) begins in the mouth where salivary α-amylase (digest α1→4) hydrolyzes the glycosidic linkages of starch (physiological pH ~6.8)
salivary α-amylase inactive in low pH of stomach, but pancreatic α-amylase secreted into small intestine is active and continues the digestion to produce maltose and maltotriose (di- and trisaccharides of glucose); these are converted to D-glucose by maltase
also remaining are the branched saccharides (α1→6) — dealt with separately
52
What is the role of pancreatic α-amylase?
Continues digestion of starch in the small intestine.
53
What is the result of glycogen catabolism?
Storage of glucose primarily in skeletal muscle and hepatocytes (liver)
glycogen phosphorylase catalyzes attack by inorganic phosphate on the terminal glucosyl residue at the nonreducing end of glycogen
glucose 1-phosphate is released
G1P is converted to G6P by phosphoglucomutase, then fed into glycolysis (reaction 2)
54
What happens to galactose in glycolysis? Catabolism
Converted to glucose 1-phosphate through phosphorylation.
created by hydrolysis of lactose to glucose + galactose in intestine
enters glycolysis after several reactions
galactose phosphorylated on C-1 (cost 1 ATP)
galactose 1-phosphate takes the uridine diphosphate (UDP) sugar-nucleotide from UDP-glucose (a product of this reaction) to generate glucose 1-phosphate for glycolysis and UDP-galactose
UDP-galactose is oxidized on C-4 to a ketone, then reduced stereospecifically at C-4 to its epimer UDP-glucose
UDP-glucose is used in step 2
UDP acts as a coenzyme carrier of hexoses (helps with catalysis)
55
Catabolism of di- and polysaccharides
Membrane-bound hydrolases in the intestinal brush border hydrolyze disaccharides.
Monosaccharides pass through intestinal cells to the bloodstream, which transports them to the liver or other tissues
56
What happens to pyruvate under anaerobic/aerobic conditions?
Anaerobic: Reduced to lactate or ethanol.
Aerobic: converted into acetyl-CoA in the mitochondria during citric acid cycle
57
How is NADH recycled in anaerobic conditions?
Through fermentation, transferring electrons from NADH to pyruvate.
58
What is the net change in NAD+ and NADH during fermentation?
2 NAD+ produced from 2 NADH.
59
Fermentation: Fate of pyruvate under anaerobic conditions
Extensive exercise, solid tumors, and erythrocytes have low levels of O2. Without O2, NADH generated during glycolysis can not be oxidized to NAD+ by mitochondria via the electron transport chain (ch.19)
organisms can regenerate NAD+ by transferring electrons from NADH to pyruvate, forming lactate
fermentation = is an energy-yielding process (2 ATP) that occurs without oxygen and regenerates NAD⁺, keeping NAD⁺/NADH levels balanced.
Lactate is further converted to glucose
60
How are inputs for glycolysis created?
A. Galactose is converted through a series of steps involving UDP to glucose 1-phosphate, which is converted to glucose 6-phosphate for glycolysis
B. Fructose is phosphorylated to fructose 6-phosphate for glycolysis
C. Dietary starch is digested by α-amylase to di- and trisaccharides of glucose, which are converted to glucose for glycolysis
D. Glycogen is converted by phosphorolysis to glucose 1-phosphate, which is converted to glucose 6-phosphate for glycolysis
E. All of these answers are correct
All of these answers are correct
61
What is microbial fermentation's end product?
Ethanol and CO2.
62
What is gluconeogenesis?
Gluconeogenesis = pathway that converts pyruvate and related three- and four-carbon compounds to glucose (mainly lactate and glycerol in mammals)
Uses seven of the ten enzymes that also act in glycolysis
occurs in all animals, plants, fungi, and microorganisms
mainly occurs in the liver in mammals
63
Where does gluconeogenesis mainly occur in mammals?
In the liver.
64
When does gluconeogenesis occur?
occurs when glucose levels are really low and there is not enough glycogen in muscle and liver to supply it (e.g. during fasting, vigorous exercise, long lectures/tests, …)
65
Why isn't gluconeogenesis simply the reverse of glycolysis?
steps are almost the reverse of glycolysis; must bypass reactions that are nearly irreversible in the cell (reactions 1, 3, 10)
bypasses are also irreversible thus glycolysis and gluconeogenesis are both nearly irreversible
note that the differences in steps mean that the chemical balance of glycolysis is not simply the reverse of gluconeogenesis
a fraction of enzymes conduct glycolysis, while another fraction conducts gluconeogenesis
glucose passes into the blood and is carried to needed tissues
energetically expensive, but essential given that the brain uses 120 g of glucose a day
66
Why isn’t gluconeogenesis = reverse of glycolysis?
glycolysis: red arrows, top to bottom
gluconeogenesis: blue arrows, bottom to top
67
What is the primary carbon source for gluconeogenesis?
* Lactate
* Glycerol
68
What is the daily glucose requirement of the brain?
120 g
## Footnote
This is essential for brain function.
69
Why is gluconeogenesis not the reverse of glycolysis?
Glycolysis has irreversible reactions that must be bypassed in gluconeogenesis.
## Footnote
These reactions are highlighted in red arrows for glycolysis and blue arrows for gluconeogenesis.
70
What is the first bypass reaction in gluconeogenesis?
Synthesis of phosphoenolpyruvate from pyruvate
pyruvate is converted to oxaloacetate in mitochondria
pyruvate carboxylase is the first regulatory enzyme in gluconeogenesis. It requires high levels of acetyl-CoA as a positive effector (produced by Fatty Acid oxidation). Lots of acetyl-CoA means lots of energy present from FA oxidation, thus turning on gluconeogenesis
mitochondrial membrane lacks an oxaloacetate transporter; oxaloacetate is reduced to malate by mitochondrial malate dehydrogenase (using NADH), transported out as malate, and then re-oxidized to oxaloacetate in the cytosol, regenerating NADH.
71
What is the first bypass reaction in gluconeogenesis?
oxaloacetate is converted to phosphoenolpyruvate in the cytosol
PEP carboxykinase uses GTP to phosphorylate and decarboxylate oxaloacetate (CO2 is removed), forming PEP
the overall equation for this set of bypass reactions is:
two competing pathways initiate gluconeogenesis, differing in NADH generation strategies
Second bypass when lactate is the glucogenic precursor
The concentration of lactate determines pathways 1 or 2
oxaloacetate is directly converted to PEP in the mitochondrion by a mitochondrial isozyme of PEP carboxykinase
cytosolic [NADH] is low and needs to be replenished for later in gluconeogenesis, but mitochondrial [NADH] is high
so, either:
cytosolic [NADH] replenished via
malate shuttling (1*)
cytosolic [NADH] replenished via oxidation of lactate to pyruvate (1**)
Regardless of 1 vs. 2, PEP continues with gluconeogenesis
72
What is the role of pyruvate carboxylase in gluconeogenesis?
It is the first regulatory enzyme in gluconeogenesis, requiring high levels of acetyl-CoA.
## Footnote
Acetyl-CoA acts as a positive effector due to its production from fatty acid oxidation.
73
How is oxaloacetate transported out of the mitochondria?
Oxaloacetate is reduced to malate, transported out, and then re-oxidized to oxaloacetate in the cytosol.
## Footnote
This process regenerates NADH.
74
What is the overall equation for the conversion of oxaloacetate to phosphoenolpyruvate?
Oxaloacetate is converted to phosphoenolpyruvate using GTP by PEP carboxykinase.
## Footnote
The ΔG for this reaction is strongly negative, making it effectively irreversible.
75
What determines the pathway choice in gluconeogenesis when lactate is the precursor?
The concentration of lactate.
## Footnote
This affects whether oxaloacetate is converted to PEP in mitochondria or cytosol.
76
What is the second bypass reaction in gluconeogenesis?
second bypass is the dephosphorylation (hydrolysis) of fructose 1,6-bisphosphate to fructose 6-phosphate
note the generation of Pi
catalyzed by fructose 1,6- bisphosphatase (FBPase-1)
FBPase-1 is regulated via phosphorylation by a kinase
## Footnote
This reaction is catalyzed by fructose 1,6-bisphosphatase (FBPase-1).
77
What is the third bypass reaction in gluconeogenesis?
third bypass is conversion of glucose 6-phosphate to glucose
as with bypass 2, this is a dephosphorylation step, this time catalyzed by glucose 6- phosphatase
note the generation of Pi
enzyme only present in hepatocytes, renal cells and epithelial cells of small intestine. Thus gluconeogenesis is only possible in these cells!
## Footnote
This is catalyzed by glucose 6-phosphatase, present only in specific cells.
78
What is required for gluconeogenesis to form one molecule of glucose from pyruvate?
6 high-energy phosphate groups, 4 from ATP and 2 from GTP
## Footnote
Also requires 2 molecules of NADH for reduction.
79
Which amino acids can be converted to pyruvate?
Almost all amino acids, except leucine and lysine.
almost all amino acids can be converted to pyruvate through an intermediate of the citric acid cycle, allowing conversion of protein -> AA -> glucose
oxaloacetate is an intermediate of the citric acid cycle, and can be fed into gluconeogenesis
useable AAs are called glucogenic
note that Leu and Lys are not glucogenic
## Footnote
These are known as glucogenic amino acids.
80
How many enzymatic reactions comprise gluconeogenesis?
11
## Footnote
The first bypass reaction has two steps.
81
What are the end products of the pentose phosphate pathway?
Ribose 5-phosphate, CO2, and NADPH
## Footnote
This pathway is important for nucleotide biosynthesis and provides reducing power for biosynthesis.
82
What regulates the fate of glucose 6-phosphate?
the relative concentrations of NADP+ and NADPH determine whether glucose 6-phosphate enters glycolysis or the pentose phosphate pathway
when NADPH is forming faster than it is being used for biosynthesis and glutathione reduction, NADPH concentration rises, and it inhibits the first enzyme in the pentose phosphate pathway (glucose 6-P dehydrogenase; previous slide)
thus, high [NADPH] shifts use of glucose 6-P away from the pentose phosphate pathway and more toward glycolysis = feedback inhibition
## Footnote
High NADPH inhibits glucose 6-P dehydrogenase, shifting glucose 6-P use toward glycolysis.
83
Pentose phosphate pathway
oxidizes and decarboxylates glucose 6-P
end products are ribose 5-P, CO2, and NADPH
the net result is the production of:
NADPH, a reductant
ribose 5-P, a precursor for nucleotide biosynthesis
It yields pentoses for nucleotide synthesis and reduced cofactors for the biosynthesis of fatty acids, sterols, and many other compounds.
## Footnote
This is an example of feedback inhibition.
84
What is gluconeogenesis?
Synthesis of glucose from simpler precursors like pyruvate and lactate
## Footnote
It is essentially the reverse of glycolysis.
85
How many enzymes from glycolysis are used in gluconeogenesis?
Seven of the ten enzymes
## Footnote
These enzymes facilitate the conversion of precursors to glucose.
86
What must gluconeogenesis bypass?
Three of the most exergonic steps in glycolysis with energetically favorable reactions unique to gluconeogenesis.
## Footnote
This is done using energetically favorable reactions unique to gluconeogenesis.
87
What is the First Bypass in gluconeogenesis?
Conversion of pyruvate to phosphoenolpyruvate (PEP) requires two exergonic reactions
## Footnote
When lactate is the glucogenic precursor, oxaloacetate is converted to PEP in the mitochondrion.
88
What enzyme is involved in the Second Bypass of gluconeogenesis?
Fructose 1,6-bisphosphatase (FBPase-1)
## Footnote
It converts fructose 1,6-bisphosphate to fructose 6-phosphate by hydrolysis.
89
What is the Third Bypass in gluconeogenesis?
Glucose 6-phosphatase catalyzes the hydrolysis of glucose 6-phosphate to glucose
## Footnote
This enzyme is found in the lumen of the endoplasmic reticulum of certain cells.
90
What is the energetic cost of gluconeogenesis?
It is energetically expensive
## Footnote
The sum of the biosynthetic reactions from pyruvate to glucose involves multiple ATP and GTP.
91
What are glucogenic amino acids?
Amino acids that can undergo net conversion to glucose
## Footnote
Their catabolism produces either pyruvate or intermediates in the Krebs Cycle.
92
What does the pentose phosphate pathway produce?
NADPH, ribose 5-P, and CO2
needed by rapidly dividing cells (bone marrow, skin, intestinal mucosa); need pentoses to make DNA, RNA, ATP, NADPH, FADH2, and coenzyme A
needed by tissues exposed directly to oxygen (RBCs, lens, cornea) because they have lots of damaging free radicals. Pentose phosphate pathway creates reducing atmosphere (high ratio of NADPH to NADP+, and high
ratio of reduced to oxidized glutathione) that minimizes oxidative damage
NADPH also needed for biosynthesis
oxidizes and decarboxylates glucose 6-P
end products are ribose 5-P, CO2, and NADPH
the net result is the production of:
NADPH, a reductant
ribose 5-P, a precursor for nucleotide biosynthesis
It yields pentoses for nucleotide synthesis and reduced cofactors for the biosynthesis of fatty acids, sterols, and many other compounds.
## Footnote
It is essential for nucleotide biosynthesis and reducing power for biosynthesis.
93
What regulates whether glucose 6-phosphate enters glycolysis or the pentose phosphate pathway?
The relative concentrations of NADP+ and NADPH
## Footnote
High NADPH concentration inhibits glucose 6-P dehydrogenase.
94
What is homeostasis in a biological context?
A property that regulates internal environment to maintain stable conditions
cells and organisms maintain a dynamic steady state
dynamic because something is always happening. Many metabolic pathways whose reactants and products are involved in other pathways
steady because as fuel enters the cell (i.e. glucose) it is catabolized, and the waste (i.e. CO2) product leaves the cell — the concentrations of other intermediate molecules remains ~constant
the mass and gross composition of a typical cell does not change appreciably over time (with the exception of aging and diseases)
cells have mechanisms to regulate metabolic pathways to achieve homeostasis — no backup or excess of any individual metabolites
failure of these mechanisms may be root of human diseases (homeostatic imbalance)
diabetes
hyperglycemia
hypoglycemia
conditions result from excess (too much) or depletion (too little) of particular metabolic product
## Footnote
This includes properties such as temperature, pH, and reaction flux.
95
What is metabolic regulation vs control?
metabolic regulation: processes that hold cellular parameters (concentration of metabolites) constant over time even as the flow of metabolites changes — homeostasis
metabolic control: process that changes the output of a metabolic pathway over time = ability to change when needed
## Footnote
It ensures that concentrations of metabolites do not fluctuate excessively.
96
What is the significance of reciprocal regulation in metabolism?
It allows for the coordination of glycolysis and gluconeogenesis
## Footnote
This coordination is crucial for maintaining energy balance in the cell.
97
What is the role of glycogen in metabolism?
Glycogen serves as a storage form of glucose
## Footnote
It provides a quick source of energy during metabolic demands.
98
What happens when there is a failure of homeostatic mechanisms?
It may lead to diseases like diabetes
## Footnote
Conditions such as hyperglycemia and hypoglycemia arise from metabolic imbalances.
99
What is the biochemical standard free energy (ΔG'°)?
Energy change under standard conditions (T=298K, P=1 atm, pH=7)
## Footnote
It is used to predict the direction of biochemical reactions.
100
Fill in the blank: Glycogen is stored as _______ in vertebrates.
glycogen granules
101
Fill in the blank: The major products of the pentose phosphate pathway include NADPH and _______.
ribose 5-P
102
What conclusion can be drawn when the equilibrium constant Keq’ and the mass action ratio Q for a reaction are small and approximately equal?
A. The concentrations of products exceed the concentrations of reactants, both at equilibrium and at the current conditions in the cell
B. The reaction is highly regulated
C. The reaction is close to equilibrium
D. The reaction is not in a dynamic steady state
E. None of the above
The reaction is close to equilibrium
## Footnote
They can also produce intermediates in the Krebs Cycle.
103
What is K_eq' in the context of chemical reactions?
Intrinsic to chemical reaction
104
What does Q represent in cellular reactions?
Controlled by cell via regulation of [E], [S], [effector]
105
When is a reaction near equilibrium?
When Q is close to K_eq' (within < 2 orders of magnitude)
106
What characterizes reactions that are far from equilibrium?
Large K_eq', much smaller Q
107
What does a small K_eq' indicate?
Favors reactants
108
What does a large K_eq' indicate?
Favors products
109
What is the role of glucagon?
Signals low [glucose] in blood and tells liver to release glucose
A peptide hormone released by pancreas to signal low [glucose] in blood, and tells liver to release glucose into blood from glycogen or gluconeogenesis
110
What is the role of insulin?
Signals high [glucose] in blood and tells liver to absorb glucose
A peptide hormone released by pancreas to signal a high [glucose] in blood, and tells liver to absorb glucose for storage into glycogen, glycolysis, …
111
What enzyme is the committed step in glycolysis?
Phosphofructokinase-1 (PFK-1)
112
What does F2,6BP do in glycolysis?
Potent allosteric activator of PFK-1
113
What is the effect of high [ATP] on PFK-1?
Inhibits PFK-1
114
What is the effect of high [ADP] or [AMP] on PFK-1?
Turns PFK-1 on
115
What are isozymes?
Different proteins that catalyze the same reaction encoded by different genes
116
What is the effect of high [citrate] on gluconeogenesis?
Favored at high [citrate], [ATP], or [acetyl-CoA]
117
Which regulatory protein competes with fructose 6-phosphate on hexokinase IV?
Regulatory protein specific to hepatocytes
118
Regulation of hexokinase IV (R1, glycolysis)
hexokinase has four different isozymes (I-IV)
muscle isozymes (I, II, III) are allosterically inhibited by their product (glucose 6-P)
hepatocyte/liver isozyme (IV) has a lower affinity (= higher Km) for glucose and not inhibited by its product (glucose 6-P)
instead, an efficient glucose transporter (GLUT2) equilibrates glucose in liver and blood. Thus, low blood [glucose] = low hepatocyte/liver [glucose]
isozyme IV activity decreases as [glucose] decreases (= sensitive to [glucose])
glycolysis slows down, and glucose is released into blood via GLUT2
119
What is the role of pyruvate kinase in glycolysis?
Catalyzes the conversion of phosphoenolpyruvate to pyruvate
120
What indicates that energy needs are being met through oxidative phosphorylation?
High [acetyl-CoA]
121
Which of the following would DISFAVOR the reaction catalyzed by phosphofructokinase-1 in glycolysis?
high [ATP]
122
True or False: High [fructose 2,6-bisphosphate] favors glycolysis.
True
123
What is the effect of glucagon on glucose consumption in the liver?
Slows the use of glucose for fuel
124
What does high [fructose 1,6-bisphosphate] indicate?
Sign that glycolysis can occur
125
What is the effect of high [long-chain fatty acids] on pyruvate kinase?
Inhibits pyruvate kinase
126
What happens to hexokinase IV at high [glucose]?
Releases hexokinase IV to return to cytosol and become active
127
What reaction does phosphofructokinase-1 catalyze in glycolysis?
The conversion of fructose 6-phosphate to fructose 1,6-bisphosphate
## Footnote
This reaction is a key regulatory step in glycolysis.
128
What does a high [ATP] level indicate about the regulation of phosphofructokinase-1?
It disfavors the reaction because ATP is a negative allosteric regulator
## Footnote
ATP also serves as a substrate in the reaction.
129
Which molecule is a positive allosteric regulator of phosphofructokinase-1?
[fructose 2,6-bisphosphate]
## Footnote
This molecule enhances the activity of phosphofructokinase-1.
130
What is glycogenolysis?
The breakdown of cellular glycogen to glucose 1-phosphate
## Footnote
This process releases monomers from glycogen granules.
131
What enzyme catalyzes glycogen breakdown?
Glycogen phosphorylase
## Footnote
This enzyme acts on glycogen to release glucose monomers.
132
What is the role of phosphoglucomutase in glycogen metabolism?
It catalyzes the reversible conversion of glucose 1-phosphate to glucose 6-phosphate
## Footnote
This reaction is crucial for linking glycogen breakdown to glycolysis.
133
Where is glucose 6-phosphate transported after its formation in the liver?
Into the Endoplasmic Reticulum
## Footnote
This transport is mediated by the G6-P transporter.
134
What is the function of glucose 6-phosphatase?
It dephosphorylates glucose 6-phosphate to release glucose into the bloodstream
## Footnote
This enzyme is present only in the liver.
135
What is the sugar nucleotide required for glycogen synthesis?
UDP-Glucose
## Footnote
UDP-glucose donates glucose for the formation of glycogen.
136
What initiates the synthesis of glycogen?
Glycogenin
## Footnote
Glycogenin acts as a primer for new chains of glycogen.
137
Which enzyme transfers glucose residues to the nonreducing end of glycogen?
Glycogen synthase
## Footnote
This enzyme forms α1-4 linkages during glycogen synthesis.
138
What is the role of the branching enzyme in glycogen synthesis?
It creates α1-6 linkages to form branches in glycogen
## Footnote
This enzyme moves glucose residues to create a branched structure.
139
What does high [ADP] indicate about the regulation of phosphofructokinase-1?
It favors the reaction because ADP is a positive allosteric regulator
## Footnote
ADP signals low energy status in the cell.
140
What is the metabolic regulation of glycogen breakdown initiated by?
Epinephrine and glucagon
## Footnote
These hormones activate signaling cascades that enhance glycogenolysis.
141
What is the key difference between glycogenolysis and glycogenesis?
Glycogenolysis is the breakdown of glycogen, while glycogenesis is the synthesis of glycogen
## Footnote
These processes are regulated reciprocally.
142
Fill in the blank: Glycogen synthesis involves the polymerization of hexoses using _______.
sugar nucleotides
## Footnote
Sugar nucleotides are formed through a condensation reaction.
143
Which of the following is true about branching in glycogen?
It creates many reducing ends
It occurs non-enzymatically
It is due to alpha1-4 linkages
Right after synthesis, each branch has at least 3 glucose residues
The amount of branching in glycogen is random
Right after synthesis, each branch has at least 3 glucose residues
## Footnote
Branching requires the action of the branching enzyme (amylo transglycolase).
144
What is the significance of having many nonreducing ends in glycogen?
It allows for rapid glycogen catabolism
## Footnote
More nonreducing ends facilitate quicker glucose release when needed.
145
What is glycogen breakdown?
The process of breaking down glycogen into glucose units for energy.
146
What is glycogen synthesis?
The process of converting glucose into glycogen for storage.
147
What regulates glycogen breakdown?
Hormones epinephrine and glucagon regulate glycogen breakdown.
148
What regulates glycogen synthesis?
Insulin primarily regulates glycogen synthesis.
149
What is the role of cAMP in glycogen metabolism?
cAMP activates PKA (protein kinase A), which influences glycogen metabolism.
150
What is the effect of epinephrine on muscle cells?
Epinephrine triggers glucose production via glycolysis for ATP.
151
What is the effect of glucagon on liver cells?
Glucagon stimulates glucose production for the blood.
152
What is the relationship between epinephrine/glucagon and glucose release?
One molecule of epinephrine/glucagon releases approximately 10,000 molecules of glucose.
153
What are the two forms of glycogen phosphorylase?
* Glycogen phosphorylase a (active) * Glycogen phosphorylase b (less active, default)
154
What is the effect of low glucose levels on phosphorylase a?
Phosphorylase a is present, promoting glycogen catabolism to make glucose.
155
What happens at high glucose levels regarding phosphorylase a?
Glucose binds to the allosteric site of phosphorylase a, inducing a conformational change.
156
What is the role of insulin in glycogen metabolism?
Insulin promotes the conversion of phosphorylase a to phosphorylase b through PP1.
157
What is glycogen synthase's default state?
Glycogen synthase a is the default state that makes glycogen.
158
How can glycogen synthase a be inactivated?
By phosphorylation of hydroxyl side chains by CKII and GSK3.
159
What is the role of GSK3 in glycogen synthesis?
GSK3 normally inhibits glycogen synthesis, but insulin inactivates it.
160
What is the function of glucose 6-P in glycogen synthase regulation?
Glucose 6-P binds to an allosteric site on glycogen synthase b, enhancing its dephosphorylation.
161
What initiates the activation of glycogen synthesis by insulin?
Insulin binding to its receptor activates receptor-bound Tyr protein kinase.
162
What is the role of PI-3K in insulin signaling?
PI-3K converts PIP2 to PIP3, which is involved in activating downstream kinases.
163
What does PDK-1 do in the insulin signaling pathway?
PDK-1 activates protein kinase PKB.
164
How does PKB affect GSK3?
PKB phosphorylates GSK3, turning it OFF and allowing glycogen synthesis.
165
What is the significance of PP1 in glycogen synthesis?
PP1 dephosphorylates glycogen synthase b to form glycogen synthase a.
166
What inhibits glycogen synthesis?
PTP1B is a protein that can inhibit glycogen synthesis.
167
What is glycogen breakdown catalyzed by?
Glycogen phosphorylase
## Footnote
It is the first enzyme involved in the glycogenolysis process.
168
Where does glycogen breakdown predominantly occur?
In the liver and little in muscle
## Footnote
Liver accounts for about 10% of its mass, while muscle accounts for 1-2%.
169
What does glycogen phosphorylase do?
Removes terminal glucose from nonreducing end of glycogen
## Footnote
It acts repetitively until it reaches a point four residues away from a (α1-6) branch point.
170
What type of enzyme is responsible for resolving the branch point in glycogen breakdown?
Bifunctional debranching enzyme
## Footnote
It uses transferase and glucosidase activities to remove and release glucose.
171
What does phosphoglucomutase catalyze?
The reversible conversion of glucose 1-phosphate to glucose 6-phosphate
## Footnote
It donates a phosphate from phosphoserine to glucose 1-P.
172
What is the role of glucose-6-phosphate in muscle?
Enters glycolysis and serves as an energy source
## Footnote
It supports muscle contraction.
173
What happens to glucose-6-phosphate in the liver?
Converted to glucose and released to replenish low blood glucose
## Footnote
This process involves glucose-6-phosphatase.
174
What is the sugar nucleotide required for glycogen synthesis?
UDP-Glucose
## Footnote
It donates glucose for glycogen synthesis.
175
What does glycogenin do?
Acts as a primer for glycogen synthesis
## Footnote
It initiates the assembly of new glycogen chains.
176
What is glycogen synthase responsible for?
Transferring glucose residue to the nonreducing end of existing glycogen
## Footnote
It creates new α1-4 linkages.
177
What is the function of the branching enzyme in glycogen synthesis?
Forms α1-6 linkages by moving glucose residues
## Footnote
It creates branches in the glycogen molecule.
178
How many glucose residues can a glycogen particle contain?
About 55,000 glucose residues
## Footnote
It has a diameter of 21 nm and a molecular weight around 10^7.
179
What are the two forms of glycogen phosphorylase?
Phosphorylase a (active) and phosphorylase b (less active)
## Footnote
Phosphorylase a is catalytically active.
180
What initiates the phosphorylation of phosphorylase b?
Hormones epinephrine and glucagon
## Footnote
They trigger cascade mechanisms for glycogen breakdown.
181
What is an enzyme cascade?
A sequence of enzymatic reactions where a catalyst activates another catalyst
## Footnote
This leads to amplification of the initial signal.
182
What role does insulin play in glycogen synthesis?
Activates phosphoprotein phosphatase (PP1)
## Footnote
This promotes the conversion of glycogen synthase b to a (active form).
183
What effect does high glucose concentration have on phosphorylase a?
Glucose binds to the allosteric site, inducing a conformational change
## Footnote
This exposes the Ser-P residue, impacting its activity.
184
What is the significance of reciprocal regulation?
It maintains homeostasis between glycolysis and gluconeogenesis
## Footnote
It ensures balanced carbohydrate metabolism.
185
What happens to glycogen synthase when it is phosphorylated?
It becomes inactive (glycogen synthase b)
## Footnote
This is facilitated by casein kinase II and GSK3.
186
What does glucose 6-P do in relation to glycogen synthase?
Binds to an allosteric site, enhancing dephosphorylation
## Footnote
This facilitates conversion to active glycogen synthase a.
187
What is the role of protein kinase PDK-1?
Activates protein kinase PKB
## Footnote
PKB phosphorylates GSK3, impacting glycogen synthesis.
188
What is the main function of glucose-6-phosphatase?
Dephosphorylates glucose 6-P in the liver
## Footnote
It is essential for glucose release into the blood.
189
What is the role of PIP in protein activation?
A ligand for and activates protein kinase PDK-1
## Footnote
PDK-1 activates PKB, which plays a crucial role in glycogen synthesis regulation.
190
What is the function of PKB in glycogen metabolism?
Phosphorylates glycogen synthase kinase 3 (GSK3), which inhibits glycogen synthesis
## Footnote
GSK3 is normally ON and inhibits glycogen synthesis.
191
What happens to GSK3 upon activation of PKB?
GSK3 is turned OFF and unable to inactivate glycogen synthesis
## Footnote
This allows PP1 to dephosphorylate glycogen synthase b.
192
What is the role of PP1 in glycogen synthesis?
Dephosphorylates glycogen synthase b to form glycogen synthase a
## Footnote
Glycogen synthase a can then synthesize glycogen.
193
Which enzyme involved in glycogenesis and glycogenolysis is allosterically regulated?
Glycogen phosphorylase, glycogen synthase, and phosphoprotein phosphatase 1 (PP1)
## Footnote
A-B-C are correct.
194
What are the three stages of cellular respiration?
1. Oxidation of fuels to acetyl-CoA
2. Oxidation of acetyl groups to CO2 in the citric acid cycle
3. Electron transfer chain and oxidative phosphorylation
## Footnote
The greatest ATP production occurs in the last step.
195
What is the significance of the citric acid cycle?
It is a nearly universal pathway that generates NADH, FADH2, and GTP
## Footnote
It is also known as the tricarboxylic acid (TCA) cycle or Krebs cycle.
196
What is the primary function of the pyruvate dehydrogenase complex?
Converts pyruvate to acetyl-CoA and CO2
## Footnote
This reaction is irreversible and occurs in the mitochondria.
197
What are the five cofactors involved in the pyruvate dehydrogenase complex?
* Thiamine pyrophosphate (TPP)
* Coenzyme A (CoA)
* Lipoate
* Nicotinamide adenine dinucleotide (NAD)
* Flavin adenine dinucleotide (FAD)
## Footnote
These cofactors are critical for enzyme function and substrate activation.
198
What role does NAD+ play in cellular respiration?
It is an oxidizing agent that carries electrons to the electron transport chain for ATP synthesis
## Footnote
NAD+ carries 2 electrons and 1 proton.
199
How is the acetyl group attached to CoA in acetyl-CoA?
By a thioester bond
## Footnote
The reactive thiol group of CoA is critical for its role as an acyl carrier.
200
What is the molecular weight and structure of the pyruvate dehydrogenase complex?
4.5 MDa and 45 nm in diameter
## Footnote
It consists of three core enzymes and regulatory proteins.
201
What is the first step in the reaction catalyzed by the pyruvate dehydrogenase complex?
Pyruvate reacts with thiamine pyrophosphate (TPP) to form a hydroxyethyl-TPP intermediate and releases CO2
## Footnote
This is the rate-limiting step.
202
What happens in the second step of the pyruvate dehydrogenase complex reaction?
The C2 carbon is oxidized from an alcohol to a ketone, and electrons reduce the lipoyl group on E2
## Footnote
This step leads to the formation of a thioester with acetate.
203
What is substrate shuttling in the pyruvate dehydrogenase complex?
Cofactors attached to the enzyme swing between active sites to transfer intermediates
## Footnote
This mechanism ensures intermediates remain within the complex.
204
True or False: The acetyl group in acetyl-CoA is formed by a redox reaction from FADH2 to FAD.
False
## Footnote
The acetyl group is attached by a thioester bond.
205
Which enzyme involved in glycogenesis and glycogenolysis is allosterically regulated?
glycogen phosphorylase
glycogen synthase
phosphoprotein phosphatase 1 (PP1)
A-B-C are correct
none of the above
A-B-C are correct
206
In the acetyl-CoA molecule formed by the pyruvate dehydrogenase complex, how is the acetyl group is attached to the CoA group?
by a lipoyllysine linker
by a thioester bond
by a TPP linker
it is formed by a redox reaction from FADH2 to FAD
none of the above
by a thioester bond
207
What are the functions of Vitamin A?
Vision, skin, immune system
## Footnote
Sources include carrots, eggs, and liver.
208
What is the primary role of Vitamin D?
Bones, calcium absorption
## Footnote
Sources include sunlight, fish, and fortified milk.
209
What does Vitamin E do?
Antioxidant, protects cells
## Footnote
Sources include nuts, seeds, and oils.
210
What is the function of Vitamin K?
Blood clotting, bone health
## Footnote
Sources include leafy greens.
211
What are the characteristics of water-soluble vitamins?
Act as coenzymes, support energy metabolism
## Footnote
Includes Vitamin B and Vitamin C.
212
What is the role of Vitamin C?
Immunity, collagen, iron absorption
## Footnote
Sources include citrus fruits and berries.
213
What is the catabolism of amino acids, fats, and carbohydrates known as?
Citric acid cycle
## Footnote
Also known as tricarboxylic acid (TCA) cycle or Krebs cycle.
214
How many stages are there in cellular respiration?
3 stages
## Footnote
1. Acetyl-CoA production, 2. Acetyl-CoA oxidation, 3. Electron transfer and oxidative phosphorylation.
215
What occurs during Stage 2 of cellular respiration?
Acetyl-CoA undergoes oxidation
## Footnote
Generates energy, material for synthesis, and waste.
216
What is the significance of oxaloacetate in the citric acid cycle?
Regulates the formation of newly synthesized oxaloacetate molecules
## Footnote
Present in very low concentration in cells.
217
What is the regulatory control of the pyruvate dehydrogenase complex (PDC)?
Inactivated by a kinase activated by ATP, activated by a phosphatase
## Footnote
This controls the formation of acetyl-CoA.
218
What is the energy yield from one cycle of the citric acid cycle?
1 ATP (or GTP), 3 NADH, 1 FADH2
## Footnote
This is the energy payoff per cycle.
219
What mnemonic can help remember the intermediates of the citric acid cycle?
Can I Keep Selling Substances For Money, Officer?
C - citrate
I - isocitrate
K - a-ketoglutarate
S - succinyl CoA
S - succinate
F - fumarate
M - malate
O - oxaloacetate
also remember succiNATE is LATE (comes after succinyl coA)
Glycolysis:
Goodness (Glucose)
Gracious, (Glucose-6-P)
Father (Fructose-6-P)
Franklin (Fructose-1,6-diP)
Did (Dihydroxyacetone-P)
Go (Glyceraldehyde-P)
By (1,3-Biphosphoglycerate)
Picking (3-phosphoglycerate)
Pumpkins (2-phosphoglycerate)
(to)
PrEPare (Phosphoenolpyruvate [PEP])
Pies (Pyruvate)
## Footnote
Each word corresponds to an intermediate.
220
What is the net ATP yield from one glucose molecule after glycolysis, pyruvate oxidation, and the citric acid cycle?
Net +32 ATP
## Footnote
This yield includes contributions from oxidative phosphorylation.
221
What is the role of anaplerotic reactions in the citric acid cycle?
Replenish intermediates
## Footnote
They ensure continuous operation of the cycle.
222
Which enzyme catalyzes a regulated step of the citric acid cycle that does not produce CO2?
Succinyl-CoA synthetase
## Footnote
It is not regulated.
223
What regulates the citric acid cycle?
Substrate availability vs. accumulating products, allosteric feedback inhibition
## Footnote
Ensures a stable steady state in the cell.
224
What is the effect of high levels of ATP on glycolysis?
Decreases the need for glycolysis
## Footnote
High ATP binds to allosteric sites and lowers affinity.
225
What type of regulation involves homotetramers with catalytic and allosteric sites?
Allosteric regulation
## Footnote
Allosteric regulation allows enzymes to be modulated by the binding of molecules at sites other than the active site.
226
What products are bound in allosteric regulation?
ADP and fructose 1,6-bisphosphate
## Footnote
These products indicate the energy status of the cell and influence enzyme activity.
227
What inhibits allosterically in the glycolysis pathway?
ATP
## Footnote
High levels of ATP signal that there is less need for glycolysis, thus inhibiting the pathway.
228
What happens to enzyme affinity when high ATP binds to the allosteric site?
Lowers affinity of enzyme for its substrate
## Footnote
This is a key mechanism in regulating metabolic pathways.
229
What are the two phases of glycolysis?
Energy investment phase and energy payoff phase
## Footnote
Glycolysis involves an initial investment of ATP and a subsequent generation of ATP.
230
What are the main inputs and outputs of glycolysis?
Inputs: glucose, Outputs: 2 pyruvate, 2 ATP, 2 NADH
## Footnote
Understanding the inputs and outputs is crucial for metabolic pathways.
231
What is the goal of fermentation?
Regenerate NAD+
## Footnote
Fermentation allows glycolysis to continue by regenerating NAD+ in the absence of oxygen.
232
What distinguishes gluconeogenesis from reverse glycolysis?
It bypasses specific steps in glycolysis
## Footnote
Gluconeogenesis is an anabolic pathway that synthesizes glucose from non-carbohydrate precursors.
233
What does the pentose phosphate pathway produce?
NADPH and ribose-5-phosphate
## Footnote
This pathway is important for nucleotide synthesis and reducing power.
234
What is homeostasis in metabolic regulation?
A dynamic steady state
## Footnote
Homeostasis ensures that metabolic processes are balanced and functioning correctly.
235
What type of metabolites discourage catabolism?
High-energy metabolites
## Footnote
These metabolites indicate sufficient energy availability, thus reducing the need for catabolic processes.
236
What is reciprocal regulation in metabolism?
One pathway increases while the other decreases
## Footnote
This mechanism helps maintain balance between opposing metabolic pathways like glycolysis and gluconeogenesis.
237
What enzymes are involved in glycogen breakdown?
Glycogen phosphorylase and debranching enzyme
## Footnote
These enzymes play critical roles in mobilizing glucose from glycogen stores.
238
What is the primary function of the pyruvate dehydrogenase complex?
Convert pyruvate to acetyl-CoA
## Footnote
This conversion links glycolysis to the citric acid cycle.
239
Where does pyruvate oxidation occur?
In the mitochondria
## Footnote
This process is crucial for aerobic respiration.
240
What are the inputs and outputs of the citric acid cycle?
Inputs: acetyl-CoA, Outputs: CO2, NADH, FADH2, ATP
## Footnote
The citric acid cycle is essential for energy production.
241
What is the net ATP produced per glucose in glycolysis, PDC, and TCA?
Approximately 30-32 ATP
## Footnote
This total includes contributions from glycolysis, pyruvate dehydrogenase complex, and the citric acid cycle.
242
Which cofactor is NOT important in the pyruvate dehydrogenase complex?
ATP
## Footnote
ATP is not a cofactor; the important cofactors include TPP, lipoate, CoA, and NAD.
243
Which enzyme catalyzes a bypass reaction in gluconeogenesis?
PEP carboxykinase
## Footnote
This enzyme facilitates the conversion of oxaloacetate to phosphoenolpyruvate.
244
What occurs when blood glucose levels are high?
PP1 is activated
## Footnote
This activation promotes glycogen synthesis and inhibits glycogen breakdown.
245
In which process is NAD+ produced from NADH?
Microbial fermentation
## Footnote
This process regenerates NAD+ for continued glycolysis under anaerobic conditions.
246
Which of the following enzymes catalyzes a step of the citric acid cycle that is regulated, but does not produce CO2?
pyruvate dehydrogenase complex
citrate synthase
isocitrate dehydrogenase
alpha-ketoglutarate dehydrogenase complex
succinyl-CoA synthetase
citrate synthase
247
Which of the following is NOT an important cofactor in the pyruvate dehydrogenase complex?
thiamine pyrophosphate (TPP)
lipoate
ATP
coenzyme A (CoA)
nicotinamide adenine dinucleotide (NAD)
ATP
248
Which of the following catalyzes a bypass reaction in gluconeogenesis?
hexokinase
pyruvate kinase
phosphofructokinase-1
PEP carboxykinase
aldolase
PEP carboxykinase
249
When the blood glucose level is high, which of the following occurs?
glucagon is released
phosphorylase kinase is activated
glycogen phosphorylase is phosphorylated
glycogen synthase is inactivated
PP1 is activated
PP1 is activated
250
In what process or enzyme complex is NAD+ produced from NADH?
- the reaction catalyzed by glyceraldehyde 3-phosphate dehydrogenase in glycolysis
- the reaction catalyzed by isocitrate dehydrogenase in the citric acid cycle
- the reaction catalyzed by succinate dehydrogenase in the citric acid cycle
- pyruvate dehydrogenase complex
- microbial fermentation
microbial fermentation
251
What product of the preparatory phase of glycolysis is required, but at twice the concentration, as a reactant in the payoff phase?
ADP
## Footnote
The preparatory phase converts 2 ATP to 2 ADP, and the payoff phase converts 4 ADP to 4 ATP, yielding a net of 2 ATP per glucose.
252
Which enzyme catalyzes the MOST exergonic reaction of glycolysis?
pyruvate kinase
## Footnote
The reaction of phosphoenolpyruvate (PEP) to pyruvate + ATP has a ΔG°′ of approximately -31.4 kJ/mol.
253
How is glucose 6-phosphate prevented from leaving the cell?
There are no phospho-glucose specific transporters
## Footnote
Phosphorylated glycolytic intermediates cannot leave the cell due to the lack of transporters.
254
What is the thermodynamic advantage for regulating glycolysis at hexokinase, rather than at phosphohexose isomerase?
salvaging one ATP
## Footnote
The reaction catalyzed by hexokinase consumes the first ATP molecule in glycolysis.
255
Which carbons of the original glucose are phosphorylated in the two molecules of glyceraldehyde 3-phosphate?
C-1 and C-6
## Footnote
C-1 becomes the phosphorylated carbon of dihydroxyacetone phosphate, and C-6 becomes the phosphorylated carbon of glyceraldehyde 3-phosphate.
256
Which reaction of glycolysis includes substrate-level phosphorylation?
phosphoglycerate kinase and pyruvate kinase
## Footnote
Substrate-level phosphorylation involves the transfer of a phosphoryl group from a substrate.
257
Which sugar CANNOT be fed into the glycolytic pathway?
cellulose
## Footnote
Most animals cannot digest cellulose due to lack of cellulase, which breaks down (β1→4) glycosidic bonds.
258
Which statement regarding fermentation is false?
It requires one enzyme to convert pyruvate to ethanol but two enzymes to convert pyruvate to lactate.
## Footnote
Lactate fermentation only requires lactate dehydrogenase, while ethanol fermentation requires both pyruvate decarboxylase and alcohol dehydrogenase.
259
Which enzyme of gluconeogenesis requires biotin as a coenzyme?
pyruvate carboxylase
## Footnote
Biotin acts as a carrier of activated bicarbonate in the carboxylation of pyruvate.
260
When lactate is the glucogenic precursor, mitochondria do not need to export malate. Why?
The conversion of lactate to pyruvate in the cytosol of hepatocytes produces NADH.
## Footnote
This conversion yields NADH, making the export of reducing equivalents unnecessary.
261
Which statement comparing hexokinase IV of the liver with hexokinases I, II, and III of muscle is false?
Hexokinase is activated by fructose 6-phosphate.
## Footnote
Hexokinase IV is inhibited by fructose 6-phosphate, with glucose competing for binding.
262
Phosphofructokinase-1 (PFK-1):
is allosterically inhibited by citrate.
## Footnote
High citrate concentration increases the inhibitory effect of ATP on PFK-1.
263
Which statement regarding the transcriptional regulation of PEP carboxykinase is false?
Insulin decreases expression of the PEP carboxykinase gene.
## Footnote
Insulin decreases the expression of PEP carboxykinase, essential for gluconeogenesis.
264
Glycogenolysis releases a form of glucose that cannot enter glycolysis. What enzyme can transform it into a glycolytic intermediate?
phosphoglucomutase
## Footnote
Phosphoglucomutase converts glucose 1-phosphate to glucose 6-phosphate.
265
In muscle, what are two allosteric activators of glycogen phosphorylase?
Ca2+ and AMP
## Footnote
Ca2+ signals muscle contraction, while AMP accumulates during ATP breakdown, activating phosphorylase.
266
A G-protein coupled receptor binds its ligand, activating a heterotrimeric G-protein that stimulates a two-fold increase in cAMP. What important result on carbohydrate metabolism do phosphorylases covalently activated by protein kinase A have?
They increase blood glucose concentration.
## Footnote
The rise in cAMP activates PKA, which phosphorylates and activates glycogen phosphorylase.
267
Glycogen synthase kinase 3 (GSK3):
phosphorylates glycogen synthase only after glycogen synthase has been phosphorylated by another kinase.
## Footnote
GSK3 requires prior phosphorylation of glycogen synthase by casein kinase II (CKII).
268
Which enzyme involved in glycogenesis and glycogenolysis is allosterically regulated?
glycogen phosphorylase
glycogen synthase
phosphoprotein phosphatase 1 (PP1)
## Footnote
Glucose and glucose 6-phosphate regulate phosphorylase and glycogen synthase allosterically.
269
Why are muscle and liver glycogen phosphorylase regulated differently?
Muscle only consumes glucose, and liver both consumes and secretes glucose.
## Footnote
Regulation serves different functions in muscle for its own needs and in the liver for blood glucose supply.
270
Strenuous physical activity in vertebrates can cause an increase in AMP levels. What is the biochemical response in carbohydrate metabolism?
an increase in fatty acid and carbohydrate catabolic pathways
## Footnote
High AMP signals metabolic stress, stimulating catabolism and inhibiting anabolic pathways.
271
Coenzyme A:
forms thioester acyl groups.
## Footnote
The —SH group of coenzyme A forms a thioester with acetate in acetyl-CoA.
272
What is the role of Coenzyme A?
Forms thioester acyl groups
## Footnote
The —SH group of mercaptoethylamine forms a thioester with acetate in acetyl-coenzyme A (acetyl-CoA).
273
What two chemical mechanisms convert pyruvate to acetyl-CoA in the pyruvate dehydrogenase complex?
Dehydrogenation and decarboxylation
## Footnote
The overall reaction is an oxidative decarboxylation where the carboxyl group is removed as CO2.
274
Which statement regarding the citric acid cycle is false?
Its role is strictly limited to energy conservation during the catabolism of the acetyl group
## Footnote
The citric acid cycle is not limited to energy conservation.
275
What does the citrate synthase step of the citric acid cycle not involve?
ATP hydrolysis
## Footnote
Synthases do not require nucleotide triphosphates such as ATP.
276
Which enzyme of the citric acid cycle is capable of substrate-level phosphorylation?
Succinyl-CoA synthetase
## Footnote
This enzyme facilitates the formation of ATP (or GTP) through substrate-level phosphorylation.
277
How many reducing equivalents are transferred to electron carriers after one turn of the citric acid cycle?
8
## Footnote
One turn generates three NADH and one FADH2, each carrying two electrons.
278
How many NADH molecules are generated from the complete oxidation of one glucose?
10
## Footnote
Glycolysis produces two NADH, and each acetyl-CoA generates three NADH in the citric acid cycle.
279
What group of molecules is produced from citrate in the citric acid cycle?
Lipids and sterols
## Footnote
Citrate can be exported to the cytosol for fatty acid and sterol synthesis.
280
Which molecule is an allosteric activator of both glycolysis and the citric acid cycle?
ADP
## Footnote
ADP activates phosphofructokinase-1 (PFK-1) and citrate synthase.
281
How is the regulation of glucose metabolism through glycolysis and the citric acid cycle coordinated?
All of the answers are correct
A. High ADP levels stimulate glycolysis and the citric acid cycle.
B. High NADH levels inhibit glycolysis and the citric acid cycle.
C. High citrate levels inhibit glycolysis.
D. In muscle, Ca2+ release (a signal of muscle contraction) stimulates both glycogen phosphorylase and enzymes of the citric acid cycle.
## Footnote
High levels of ADP and Ca2+ stimulate both pathways, while high NADH inhibits them.
282
Which statement regarding regulation of the citric acid cycle is false?
As [NADH]/[NAD+] increases, flux through the cycle increases
## Footnote
High [NADH]/[NAD+] ratios inhibit the cycle's activity.
