BIOCHEM EXAM 3
LECTURE 27/28
1. What is the average adult’s amount of total energy reserve?
A: 166,000 kcal
2. 1lb of adipose tissue is equal to how many kcal?
A: 3,500 kcal
3. 1lb of muscle is equal to how many kcal?
A: 365 kcal
4. The energy fuel reserve consists of lipids, proteins, and carbohydrates in what percentages?
A: Lipids ~85%, Protein ~15%, Carbohydrates ~0.5%
5. What is the electron transport chain (ETC)?
A: A series of proteins and compounds that receive electrons from NADH and/or FADH2
(generated by TCA cycle) and transfer these electrons to molecular oxygen to form water.
6. What is oxidative phosphorylation?
A: The process of synthesizing ATP from ADP + Pi using the energy of the proton gradient
generated by ETC
7. What processes produce acetyl CoA and TCA cycle intermediates?
A: Glycolysis, fatty acid oxidation, and the oxidation of amino acids
8. What is the driving force of ATP synthase?
A: The ETC produced proton gradient
9. What is the site of TCA cycle and fatty acid oxidation?
A: Mitochondria
10. Which mitochondrial membrane is impermeable to almost everything? Which is permeable?
A: Inner mitochondrial; outer mitochondrial
11. What are porins? Where are they found?
A: Proteins in the outer membrane that allow diffusion of ions and water soluble
metabolites
12. Where are the ETC and ATP synthase embedded?
A: Inner membrane
13. Where is ATP produced? Where is it sent?
A: In the matrix; to the cytoplasm
14. Who developed the chemiosmotic theory? When? When did he win a Nobel prize?
A: Peter Mitchell; early 1960s; 1978
15. What occurs in Complex I of the ETC?
A: NADH transfers a hydride ion to FMN, which eventually leads to electron transfer to
coenzyme Q and the transport of 4H+ into inter membrane space.
16. What occurs in Complex II of the ETC?
A: FADH2, created in TCA cycle by succinate dehydrogenase, transfers its electrons, which
eventually end up with coenzyme Q. NO proton transport.
17. Complex I, II, and flavoproteins donate electrons to what part of the ETC?
A: Coenzyme Q
18. How many protons are transported to inter membrane space in complex I and II?
A: 4 H+
19. What is coenzyme Q?
A: It is a lipid soluble cofactor that resides in the inner mitochondrial membrane. It accepts
2 e- and 2 H+ and transfers the electrons to complex III
20. Errors in the CoQ reaction result in e- transfer to O2, which leads to formation of what?
A: Superoxide O221. What is the central player in accepting electrons in the ETC?
A: Iron
22. What are cytochromes?
A: They are proteins containing a heme cofactor, which varies in structure and reduction
potential.
23. What happens in Complex III?
A: CoQ transfers two electrons to Complex III and releases 2 H+ into inter membrane space.
Complex III transfers the electrons to cytochrome c and 2 additional H+ are transported into
inter membrane space.
24. What happens at Complex IV?
A: Complex IV accepts 2e- from cyt c. The e- are transferred one at a time to O2, which form
H2O. 2 H+ are transported into the inter membrane space.
25. What is Complex IV usually referred to as?
A: Terminal oxidase
26. How many H+ are transported into the inter membrane space per NADH? Per FADH2?
A: 10 H+; 6 H+
27. What drives the ETC?
A: ΔE0’ –electrons flow spontaneously from a molecule with more negative to a molecule
with a more positive E0’
28. What are the two NADH shuttles that transfer electrons from cytoplasmic NADH into the
mitochondria?
A: Malate-Aspartate shuttle (heart, brain, red muscles) and Glycerol 3-phosphate shuttle
(white muscles)
29. What does proper functioning of oxidative phosphorylation require (5 things)?
A:
 All of the components of the ETC
 ATP synthase
 Oxygen
 Reducing coenzymes
 Intact mitochondrial membrane
30. What is the driving force for H+ movement?
A: The proton concentration gradient and membrane potential difference
31. What does the membrane portion (F0) of ATP synthase do? The matrix portion (F1)?
A: Translocates H+; synthesizes ATP
32. How does ATP synthase function?
A: A proton binding to F0 drives rotation of the c subunits, which makes γ rotate stimulating
a conformational change in F1β subunits, which produce ATP
33. Describe the binding change mechanism of ATP synthase.
A: The ATP synthase has 3 β subunits. Each subunit has an “active” site. These subunits do
not move. ATP is in one unit, ADP + Pi is in one unit, and nothing is in the third unit. As γ
moves, it stimulates the release of ATP, forming an empty site. Former empty site binds ADP
+ Pi, ATP is formed in the third site. This process continues as long as γ moves
34. How does ATP-ATP translocase function?
A: It pulls an ADP into the matrix while pumping an ATP out to the inter membrane space
35. How does the Pi get into the matrix?
A: It does this by symport with a H+ moving back into the matrix
36. What controls the rate of oxygen consumption?
A: Concentration of ADP and phosphate
37. What are other processes the H+ gradient drives?
A: Pyruvate transport, ATP-ADP translocase antiport, and Pi/H+ symport
38. What inhibitor shuts down the ETC at complex I? How many H+ transported?
A: Rotenone; 0
39. What inhibitor blocks Complex II? How many H+ transported?
A: Malonate; 4 from Complex I
40. What inhibitor blocks Complex III? How many H+ transported?
A: Antimycin-A; 4 from Complex I
41. What inhibitor(s) block at Complex IV? How many H+ transported?
A: CO, N3-, and CN-; 8 H+ from Complex I and III from NADH; 4 from Complex III FADH2
42. What inhibitor blocks ATP production? How many H+ transported?
A: Oligomycin; 10 H+ from Complex I, III, and IV from NADH; 6 from Complex III and IV for
FADH2
43. What does it mean to “uncouple?”
A: Any agent that allows H+ to leak back into the matrix separate ETC from ATP synthesis.
ETC continues but ATP production stops.
44. What happens to the energy of the proton gradient?
A: It is converted to heat rather than ATP
45. What are some chemical uncouplers? Natural uncouplers?
A: 2,4-dinitrophenol, dicumarol, salicylate; microbial toxins and uncoupling proteins (UCP1—thermogenin)
46. What stimulates heat generation in infants?
A: Thermogenin activation by free fats from brown fat
47. What is DNP?
A: It is a proton carrier that readily crosses membranes and prevents electrochemical H+
gradient across inner mitochondrial membrane.
48. What was DNP previously used for? What does it cause?
A: Weight loss; blindness
49. What are some (4) mitochondrial myopathies?
A:
 Deficiency in mitochondrial ETC
 Cyanide poisoning
 Hypoxic injury
 Malignant hyperthermia
50. What are the side effects of deficiency in mitochondrial ETC?
A: Weakness, cramping, severe fatigue
51. How does cyanide poisoning affect ETC?
A: It inhibits mitochondrial ETC at cytochrome oxidase
52. What is the result of hypoxic injury?
A: Without oxygen there is no ATP production and no muscle function
53. What triggers malignant hyperthermia in mitochondrial myopathies?
A: Major anesthetics result in the uncoupling of ox. Phos from ETCATP production
decreases
54. What is the body’s reaction from this heat production?
A: The TCA cycle is stimulated which leads to excessive CO2 production and respiratory
acidosis
LECTURE 29
1. What is the universal fuel for human cells?
A: Glucose
2. What energy equivalents does Glycolysis produce?
A: 2 moles NADH and 2 moles of ATP per mole of glucose
3. What is glycolysis the pathway of production for?
A: Oxidation of glucose to pyruvate
4. If O2 and mitochondria are available, where does pyruvate enter in metabolism?
A: The TCA cycle where it is completely oxidized to CO2
5. If no O2 or mitochondria, what happens to pyruvate?
A: It is converted to lactate
6. Is glycolysis an aerobic or anaerobic process?
A: Anaerobic
7. What pathways does glycolysis produce precursors for?
A: Pentose phosphate pathway, amino acid biosynthesis, fatty acid synthesis
8. What glycolysis product forms the backbone for triacylglyceride synthesis?
A: Glycerol 3-phosphate (G3P)
9. What glycolysis product can be converted to an allosteric inhibitor of oxygen binding Hb?
A: 1,3-bisphosphoglycerate
10. Where does glycolysis occur?
A: In the cytosol
11. What are the major products from glycolysis?
A: 2 pyruvate, 2 NADH, and a net gain of 2 ATP
12. What is the first phase of glycolysis?
A: ATP-utilizing steps
13. What are the ATP-utilizing steps?
A: ATP-dependent phosphorylation of glucose at 2 sites activates the glucose (Fructose 1,6bisphosphate)cleavage of molecule into two triose phosphates
14. What is the second phase of glycolysis?
A: ATP-generating steps
15. What commits glucose to cells?
A: Phosphorylation
16. What is a common intermediate for pathways that use glucose?
A: Glucose 6-phosphate
17. Where is glucokinase found? What is glucokinase affinity for glucose?
A: in the liver and pancreatic β cells; low affinity, high Km
18. What carries glucose from the small intestine to the liver?
A: Portal vein
19. What commits glucose to glycolysis and is the most important control point for glycolysis?
A: Phosphofructokinase 1 (PFK-1)
20. What are characteristics of PFK-1?
A: Thermodynamically irreversible, commits glucose to glycolysis, rate limiting step for
glycolysis
21. What is fructose 1,6-bisphosphate cleaved into?
A: Glyceraldehyde 3-phosphate and dihydroxyacetone phosphate
22. Of the two trioses, which is the only one that can move forward in glycolysis? What happens to
the other?
A: G3P; dihydroxyacetone phosphate is isomerized to G3P by an isomerase
23. What type of phosphorylation produces one ATP per G3P?
A: Substrate level phosphorylation
24. What is one of the highest energy compounds known?
A: Phosphoenolpyruvate (PEP)
25. What makes PEP?
A: Enolase
26. How does PEP create a pyruvate?
A: Through substrate level phosphorylation; gives ADP a phosphateproduce pyruvate
27. How is the NAD+, needed to keep glycolysis running, generated?
A: From the ETC
28. Can NADH permeate the inner mitochondrial membrane?
A: No
29. How does NADH produced by glycolysis transfer its electron to the ETC?
A: through glycerol 3-phosphate or malate/aspartate shuttle system, which can cross
through the membrane
30. How does the G3P shuttle system work?
A: NADH reduces G3P which easily crosses the outer mitochondrial membrane and binds to
FAD-containing protein embedded in the inner mito membranee- transferred to FAD,
reducing it to FADH2e- passed to CoQ in ETC, which leads to 1.5 mole of ATP produced
31. Describe the malate/aspartate shuttle system.
A: NADH reduces oxaloacetate to form malate, which passes through the inner mito
membranein the matrix, malate reduces NAD+ and forms NADH and oxaloacetateNADH
enters ETC so 2.5 moles of ATP can be produced
32. What happens to pyruvate in anaerobic conditions?
A: It is converted to lactate to regenerate NAD+
33. What happens to the lactate?
A: It is released into the blood and picked up by the liver and heart where it is an important
precursor for glucose synthesis (liver) and acetylCoA production (heart)
34. What are some tissues that rely on anaerobic glycolysis?
A: Mature erythrocytes, skin cells, tissues in the eyes, muscle
35. When does lactate production occur in muscles?
A: When need for ATP exceeds ability of mitochondria to make ATP
36. What is it called when lactate cycles between liver and muscle?
A: The Cori Cycle
37. What is the adenylate charge?
A: shows that energy status of the cell controls reactions
38. What pathways are inhibited by high energy charge?
A: Catabolic
39. What pathways are stimulated by high energy charge?
A: Anabolic
40. What is the normal range of the adenylate charge?
A: 0.8 to 0.95
41. What happens below AC range?
A: Catabolic pathways dominate
42. What happens above AC range?
A: Anabolic pathways dominate
43. What does adenylate kinase do?
A: Converts 2 ADP to ATP and AMP
44. What activates PFK-1?
A: AMP and Fructose 2,6-bisphosphate
45. What inhibits PFK-1?
A: ATP
46. The glycerol-3 phosphate / dihydroxyacetone phosphate shuttle system carries the reducing
power of NADH to the inner mitochondrial membrane electron transport chain. What is the fate of
the electrons carried by this shuttle?
a. The electrons are transferred to Complex I resulting in the formation of 2.5 ATP per
cytoplasmic NADH used.
b. The electrons are transferred to a flavoprotein, resulting in the formation of 1.5 ATP per
cytoplasmic NADH used.
c. The electrons are transferred to Complex III, resulting in the formation of 1.5 ATP per
cytoplasmic NADH used.
d. The electrons are transferred by a coupled reaction to the malate-aspartate shuttle system
for transfer into the mitochondria.
A: B
47. In the absence of mitochondria or molecular oxygen, pyruvate generated by glycolysis is
a. phosphorylated to phosphoenolpyruvate to make glucose.
b. converted to oxaloacetate to stimulate the TCA cycle.
c. reduced to lactate, generating one NAD+
d. oxidized to lactate, generating one NADH
A: C
LECTURE 30
1. What is the major source of energy for ATP synthesis in humans?
A: Fatty acid oxidation
2. What is the major pathway of FA oxidation and what does it produce?
A: β-oxidation in the mitochondria; generate acetyl CoA which enter TCA and produces ATP
3. Muscle tissues oxidize FA to what?
A: CO2 and H2O
4. Why do they brain and nervous tissue not use FA as a major source of energy?
A: Can’t import fat across the blood-brain barrier
5. Why can’t RBCs oxidize FAs?
A: No mitochondria
6. What protein in the blood carry FA?
A: Albumin
7. What do muscles use for ATP production?
A: β-oxidation
8. What happens to FA in liver?
A: β-oxidized into acetyl CoA, which is converted to ketone bodies to be used as fuel source
for other tissues
9. Where are ketone bodies used as energy?
A: Muscle and kidney; brain and nervous tissue if concentration is high
10. Why can’t liver use KB? RBC?
A: Lack enzymes for activation; lack mitochondria
11. What determines the enzymes used and location of the pathway for FA?
A: FA chain length
12. Differentiate between the chain lengths (4).
A:
 Short: 2-3 Carbons
 Medium: 4-12 Carbons
 Long: 12-20 Carbons
 Very long: >20 Carbons
13. What is the predominant chain of FA in the body?
A: Long
14. What is the goal of FA activation?
A: To get FA bound to CoA = fatty acyl CoA
15. Describe the activation of FA.
A: Acyl CoA synthetase attaches an AMP group to the FA carboxylic acidforms fatty acylAMP + PPiFA attached to AMP is transferred to CoA to form fatty acyl CoA
16. Where are short chains activated? Medium? Long?
A: cytosol or mitochondrion; mitochondrial matrix; enzymes located in the ER membrane,
inner mito mem, and peroxisomal mem
17. How is long chain fatty acyl CoA transported into mitochondria?
A: Fatty acyl CoA moves into inner membrane spacewith help of CPT, fatty acyl CoA
removes CoA and adds carnitineforms CoA and fatty acylcarnitinespecific translocase on
inner mito mem transports fatty acylcarnitine into matrixenzyme transfers FA from fatty
acylcarnitine back to CoA and carnitine uses translocase to move back into inner membrane
space
18. β-oxidation only occurs in what organelle?
A: Mitochondrion
19. How are fatty acids with even numbers oxidized?
A: Two carbons adjacent to the CoA are noted as α and β. Two H+ and 2e- are transferred to
FAD forming FADH2trans double bond formed between α and β carbonsH2O adds
across double bond forming a β-hydroxacyl CoA β-hydroxacyl CoA is oxidized by NAD+
forming β-ketoacyl CoAbond between α and β carbons is cleaved by addition of a second
CoA moleculeProduces CoA and a fatty acyl CoA that is 2 carbons shorterrepeats until
final product is 2 moles of acetyl CoA
20. What is ETF QO and what does it do?
A: Electron-transferring flavoprotein coenzyme Q oxidoreductase; flavoprotein in inner
mito matrix that receives electrons and gives them to CoQ
21. How many moles of ATP are produced by the first two carbon unit oxidation?
A: 11 moles ATP
22. How many moles of ATP are produced by the subsequent two carbon units utilized?
A: 13 moles
23. How much ATP does a typical FA produce?
A: ~100 moles ATP
24. How much ATP does a molecule of glucose produce?
A: 38 moles of ATP
25. What is the process of β-oxidation for odd chains of FAs?
A: Same process as even chains until final 5 carbons; final reaction generates 1 acetyl CoA
and one propionyl CoA (3 Carbons)
26. What happens to propionyl CoA?
A: It is carboxylated to methylmalonyl CoA, which is converted to succinyl CoA and enters
the TCA cycle
27. What must happen for β-oxidation to occur on unsaturated FA?
A: Double bond must be in trans between the α and β carbons
28. What enzymes do this remodeling of the double bond?
A: Isomerase and reductase
29. What is the effect of double bonds on ATP production?
A: They reduce amount of ATP produced because of different requirements for NADH or
FADH2 production
30. What is the purpose of peroxisomes in FA oxidation?
A: They are to break down very long chain FA into smaller units that can be moved into the
mitochondria via carnitine shuttle for oxidation
31. How do NADH and FADH2 levels affect FA oxidation?
A: High levels will lead to inhibition of FA oxidation because there is no need for ATP
production
32. Where does synthesis of KB primarily occur?
A: Liver mitochondria
33. What are the major KB?
A: Acetoacetate, β-hydroxybutyrate, and acetone
34. What conditions make it favorable for KB formation?
A:
 Fasting, starvation, or high fat, low carb diet
 High acetyl CoA, NADH and ATP

High glucagon/insulin ratio
35. How are ketone bodies synthesized?
A: Two acetyl CoA react to form acetoacyl CoAreacts with third acetyl CoA to produce 3hydroxyl-3-methyl glutaryl CoA (HMG CoA)cleaved to acetoacetate and acetyl CoA
36. What are the fates of acetoacetate?
A:
 Enter blood stream to be utilized by other tissue
 Reduced by NAD+-dependent dehydrogenase to form β-hydroxybutyrate
 Spontaneously decarboxylate forming acetone
37. What form of KB do humans favor?
A: β-hydroxybutyrate
38. What ratio is key determinant for the relative amount of each KB?
A: NADH/NAD+
39. How is acetone ridded?
A: Expired from the lungs
40. How is acetoacetate used in cells?
A: β-hydroxybutyrate reaction reversed to form acetoacetate and NADH, which is used to
generate ATP from ox phosphorylation
41. More energy is obtained from which KB?
A: β-hydroxybutyrate
42. How are KB oxidized?
A: Succinyl CoA combines with the acetoacetate to form succinate and acetoacetyl
CoAcombines with a new CoA resulting in the formation of two molecules of acetyl CoA
43. Two moles of acetyl CoA produced from KB oxidation enter the TCA cycle to produce how much
ATP?
A: 18 moles ATP
44. What are advantages of energy produced using KB derived from FA?
A:
 Liver only partially oxidizes FA to KB
 Other tissues can use the KB as fuel
 Brain can use KB during starvation, decreasing need for glucose
 Decreased use of muscle protein AA’s as carbon source for glucose production
45. Do muscles prefer FA or KB for fuel? Why?
A: FA because greater amount of ATP per mole of FA
46. High FA shuts down what enzyme?
A: Pyruvate dehydrogenase
47. What happens to FA oxidation and KB utilization following a high carb meal?
A: FA synthesis is turned on, which leads to no FA oxidation and no production of KB
48. What happens to FA oxidation and KB utilization during fasting/starvation?
A: FA synthesis is turned off, which allows carnitine shuttle to be operative. This leads OAA
and malate toward glucose production, which leads to an accumulation of acetyl CoA thus KB
production
49. Fatty acids are the most efficient fuel source of most tissues. Why is this?
a. Fatty acid oxidation can be used by more tissue types than glycolysis.
b. The compartmentalization of fatty acid oxidation in mitochondria is more efficient for the
electron transport chain and ATP synthase.
c. A typical fatty acid produces about 50 ATP molecules, whereas a glucose molecule yields
about 36 ATP molecules.
d. A typical fatty acid yields about100 ATP molecules whereas a glucose molecule yields only
about 30 ATP molecule
A: D
50. A medical student studied so hard for his / her biochemistry exam that he / she did not eat for
nearly two days up to the time of the exam. What was the primary fuel source available for the
student’s brain at the time of the exam?
a. Glucose
b. Fatty acids
c. Ketone bodies
d. Cholesterol
A: A, Brain will use glucose as much as it can. Only after about 5 days when the glucose
supply is dropping down and the KB concentration is building up will brain start to import
KB to replace the glucose it normally uses.
51. What is the starting material for ketone body synthesis?
a. Acetyl CoA
b. Acetone
c. Dihydroxyacetone phosphate
d. Glucose
A: A
LECTURE 31/32
1. How is oxygen essential to life?
A: Detoxification, Biosynthesis, and Final electron acceptor in the production of ATP in the
mitochondria
2. How is oxygen toxic?
A: Oxyradicals damage cell membrane, proteins, lipids, and DNA
3. Describe the electronic structure of oxygen.
A: It is a biradical meaning it has two antibonding electrons with parallel spins. The spin
restriction prevents C-H organisms from spontaneously combusting in oxygen rich
atmospheres. Most oxidation occurs by transfer of single electrons to O2
4. What enzymes can transfer single e- to O2 via a metal  ROS?
A: oxidases, peroxidases, and oxygenases
5. Describe the step wise reduction of oxygen.
A: O2+e-  Superoxide 02-02- + e- + 2H+H2O2H202 + e- + H+  H2O + OH. 
OH. + e- + H+  H2O; 2 H2O produced
6. Describe the relationship between ROS and Parkinson’s disease.
A: The production of ROS in neuronal cells leads to dysfunction in the cells/death of cells.
This leads to decreased amounts of dopamine, which triggers Parkinson’s disease
7. Describe the process of lipid peroxidation.
A: Lipid radicals are derived by lipid oxidation. The result of this leads to oxidized
breakdown of products.
8. What is an indicator of free radical tissue damage?
A: Malondialdehyde (MDA) formed from lipid peroxidation
9. What is lipofuscin? What are lewy bodies?
A: A heterogeneous mixture of cross-linked polymerized lipids and protein formed by
reactions between amino acid residues and MDA. They are autophagocytized by lysosomes
but cannot be digested. Lewy bodies are lipofuscin material built up in degenerating
neuronal cells
10. What is the effect of ROS on proteins? What AA are particularly susceptible?
A: Fragmentation, cross-linking, aggregation, susceptible to proteolytic digestion; Proline,
histidine, arginine, cysteine, and methionine
11. What is the effect of ROS on lipids?
A: Membrane damage and aldehydes produced that can cross-link proteins
12. What is the effect of ROS on DNA?
A: Breaks the DNA strand and causes base alteration
13. What are the major sources of ROS?
A:
 Endoplasmic drug metabolism (Cyt P450)
 Mitochondrial ETC
 Ionizing radiation
 Enzymes
 Phagocytes
 Autoxidation of drugs and biomolecules
o Hemoglobin, epinephrine, thiols, phenyl-, hydrazine
14. Where is cytochrome P450 abundant in the body?
A: Endoplasmic reticulum of liver cells
15. What energizes cytochrome P450 reductase?
A: NADPH
16. What is the function of cytochrome P450?
A: It tries to add oxygen to foreign materials to make them more soluble in the body, in the
process creating ROS
17. What type of compounds are most of the substrates of cytochrome P450?
A: Lipid-soluble compounds
18. What are xenobiotics?
A: They are the substrates for Cyt P450. The can be drugs, alcohol, anesthetics, dyes, or
pesticides
19. Approximately how many different P450 isoenzymes are there?
A: ~100
20. What molecule leads to ETC leakage of ROS? How?
A: CoQ; CoQ loses an electron that binds to O2 creating O221. What is the effect of electron leakage at CoQ?
A: Decreased/no ATP production
22. Why is mitochondrial DNA susceptible to damage of ROS more than nuclear DNA?
A: Nuclear DNA is protected by histones and mitochondrial DNA is in an environment where
ROS are frequently produced
23. What are some cytoplasmic enzymes that generate ROS or RNOS?
A:
 Xanthine oxidase
 Aldehyde oxidase
 Dihydrooratate dehydrogenase
 Monoamine oxidase (MAO)
 Flavo enzymes
 Nitric oxide synthase
24. What is the function of ROS production in phagocytes?
A: Effective killing of bacteria
25. What is hairy cell leukemia?
A: A superoxide defect in PMN leukocytes
26. What is associated with the continuous production of oxidants at the site of chronic
inflammation?
A: Cancer
27. What are the three isoforms of nitric oxide synthase?
A: inducible (iNOS), neuronal (nNOS), and endothelial (eNOS)
28. What NOS are regulated by Ca2+? What is the effect of these isoforms in smooth muscle cells?
A: eNOS and nNOS; relaxation of smooth muscle cells
29. What is iNOS responsible for?
A: ROS/RNS production, which leads to microbial killing, inflammation, DNA damage, and
protein/lipid damage
30. What is the function of NO in its gaseous state?
A: damage DNA, proteins and lipids; at low concentrations acts as a hormone or
neurotransmitter causing vasodilation; at high concentrations causes tissue damage
31. How are nitric oxide radicals formed?
A: Transforming arginine to citrulline via NOS
32. True or False. It takes very little ROS to activate antioxidant enzymes.
A: True
33. Adding what to the diet can help avoid the destruction of healthy cells by free radicals?
A: Antioxidants
34. What are the two categories of defense against ROS?
A: Small molecular weight and large molecular weight
35. What are the three categories of small molecular weight defense?
A: Dietary antioxidants, Endogenous antioxidants, and Drugs/Chemicals
36. What are the dietary antioxidants?
A: Vitamin A, C, E and flavonoids (tea, chocolate)
37. What are endogenous antioxidants?
A: Uric acid, HDL, melatonin, and glutathione
38. What are the large molecular weight defenses?
A: Superoxide dismutase (SOD), catalase, GSH peroxidase, and phase 2 enzymes
39. How does SOD function?
A: 2 O2- molecules react with SOD, which adds 2 H+ and forms H2O2 and O2
40. How does catalase function?
A: H202 reacts with catalase and H202 to form 2 H2O and O2
41. How do GSH peroxidase and GSH reductase function?
A: GSSG is reduced by GSH reductase to form 2 GSH molecules. H2O2 reacts with GSH
peroxidase, which oxidizes GSH to form 2 H2O molecules and a GSSG molecule
42. Where does glutathione oxidation occur?
A: Cytoplasm
43. What acts as a defense layer in the lung against O3 (ozone)?
A: GSH, Ascorbic acid, and uric acid
44. What is a powerful antioxidant enzyme that blocks the oxidization of LDL cholesterol?
A: Lechitin-cholesterol acyltransferase
45. What is involved in the detoxification of electrophilic xenobiotics and absorbs/detoxifies ROS,
directly or indirectly?
A: Phase 2 enzymes
46. True or False. Antioxidants aid in the phase 2 defense network.
A: True
47. What molecule reduces GSSG to GSH?
A: NADPH
48. What reduces oxidizes GSH?
A: GSH peroxidase
49. What is a byproduct of heme breakdown and a powerful antioxidant?
A: Bilirubin
50. What sequesters O2 not allowing for the production of ROS?
A: Ferritin
51. What are some lifestyle changes to help tip the balance toward healthiness?
A: Diet, exercise, stress reduction, and sleep
LOOK OVER NUTRITION POWER POINTS (LECTURE 33/34) AND REVIEW THE
INTESTINAL PIPELINE!!!!!
LECTURE 35
1. How much dietary fuel is ethanol responsible for?
A: 7 kcal/g
2. How is ethanol absorbed and where is the majority metabolized?
A: Absorbed by passive diffusion in GIT and metabolized in the liver
3. What is alcohol normally metabolized in to?
A: Acetate
4. Describe the 2 step metabolization of alcohol.
A: Ethanol reacts with alcohol dehydrogenase in the cytoplasm of hepatocytes to produce
acetaldehyde. Acetaldehyde reacts with acetaldehyde dehydrogenase in the mitochondria of
hepatocyte to form acetate
5. What cofactor does alcohol metabolization produce?
A: NADH
6. What happens to the acetate produced?
A: It enters blood and is taken up by muscle and other tissues and is converted to acetyl CoA
for use in the TCA cycle
7. What is the effect of acute alcohol metabolism?
A: Increased NADH/NAD+ ratio, which leads to FA oxidation inhibition and ketogenesis. It
also leads to lactic acidosis, which inhibits gluconeogenesis.
8. What is the effect of chronic alcohol metabolism?
A: Hepatic steatosis, alcohol-induced hepatitis, cirrhosis, and increased acetaldehyde and
free radicals, which damage liver cells, proteins, lipids, and DNA
9. What are alcohol dehydrogenases?
A: They are a family of cytoplasmic enzymes with various specificities for different alcohols.
10. What is the most common ADH? What does it have the highest affinity for?
A: Class I; ethanol
11. Where is Class I ADH located?
A: Liver
12. What are the two classes of acetaldehyde dehydrogenase (ALDH)? Functions?
A: ALDH1 is cytoplasmic and picks up excess acetaldehyde if necessary; ALDH2 oxidizes
80% of acetaldehyde, producing 1 NADH
13. What are MEOS? How do they function?
A: Microsomal Ethanol Oxidizing Systems; They are an enzyme based system that oxidizes
about 10-20% of ethanol. They contain cytochrome P450 mixed-function oxidase isozyme
(CYP2E1). Electrons from ethanol and NADPH are used to reduce O2 to water and you get
acetaldehyde production without NADH generation.
14. What is the problem with MEOS?
A: Increased ROS generated and cytoplasmic acetaldehyde, which can be toxic.
15. What occurs with low levels of ethanol? High levels?
A: Liver metabolism; liver metabolism +MEOS activation
16. Expression of various P450 enzymes leads to what?
A: Tolerance
17. What P450 molecules is ethanol a potent inhibitor of?
A: CYP2B1 and CYP2B2
18. What factors lead to developing chronic alcoholism, alcohol-induced liver disease, and increased
risk of some cancers?
A:
 Genotype—enzyme polymorphisms and activity
 Drinking history: chronic consumption decreases ADH and CYP2E1
 Gender: Blood alcohol levels generally greater for females than males
 Quantity
19. What is the energy yield of EtOH in liver? MEOS?
A: 2 NADH (+5 ATP), acetyl CoA formation (-2 ATP), TCA Cycle (+9 ATP and +1 GTP)12
ATP +1 GTP; 1 NADPH consumed (-2.5 ATP), 1 NADH produced (+2.5 ATP), acetyl CoA
formation (-2 ATP), TCA cycle (9 ATP + 1 GTP)7 ATP + 1 GTP
20. What are the two phases of alcohol-based liver disease?
A: Reversible effects and irreversible effects
21. What are the reversible effects of alcohol-based liver disease?
A: Inhibition of FA oxidation and stimulation of TG synthesis, leading to fatty liver.
Ketoacidosis or lactic acidosis, which leads to hypoglycemia or hyperglycemia
22. What are the irreversible effects of alcohol-based liver disease?
A: Acetaldehyde and free radicals can cause alcohol-induced hepatitis, where liver cells can
become necrotic and die. Cirrhosis, caused by fibrosis, which obstructs blood flow leading to
loss of liver function and hepatic failure
23. What ratio shuts down FA oxidation?
A: High NADH/NAD+ raito
24. What occurs when FA oxidation shut down?
A: FA accumulate in the liver and are reincorporated into TGs for storage. TGs are packaged
into VLDLs for export but they accumulate in the liver leading to hepatic steatosis.
25. How does alcohol-induced ketoacidosis occur?
A: Ethanol metabolism produces NADH to convert all oxaloacetate to malate, which
prevents acetyl CoA from entering TCA cycle leading to a sharp rise in acetyl CoA levels. High
levels of CoA lead to KB synthesis. Because alcohol is metabolized to acetate, acetate is a
preferred substrate over KB, so KB not utilized and blood levels increase. KB are weak acids
leading to decreased body pH.
26. What are the two forms of ketoacidosis? Causes?
A: Alcoholic—caused by excessive alcohol consumption; diabetic—complication of DM
caused by build up of KB from fat metabolism, which occurs when glucose is not available as
a fuel source for the body.
27. How are ketones eliminated?
A: In urine, sweat and breath
28. Alcohol metabolism leads to increase in NADH, how does this affect pyruvate/lactate
equilibrium? What is the effect of this on body?
A: Pushes pyruvate towards lactate production; acidosis and hypoglycemia or
hyperglycemia
29. How does the disease state of gout occur?
A: High blood lactate levels decreases the excretion of urea, so urea accumulates as uric acid
crystals in joints
30. How can high NADH levels result in hyperglycemia and hypoglycemia?
A: High NADH levels decreases pyruvate availability for gluconeogenesis leading to
hypoglycemic conditions; high NADH levels also inhibits glycolysis, resulting in a higher BG
level than normal
31. How is acetaldehyde toxic?
A: It is a very reactive compound, forming adducts with amino groups, sulfhydryl groups,
nucleotides, and glycerophospholipids.
32. How does acetaldehyde-adduct lead to hepatitis?
A: Liver can’t produce the vital proteins: albumin, coagulation factors, and binding proteins
for vitamins, steroids, and iron. Acetaldehyde-adduct formation leads to export machinery
damage, so liver cannot export VLDL and other lipoproteins. Proteins accumulate, water
moves in to compensate, liver swells and disrupts structure and portal vein flow.
33. How does acetaldehyde affect free radical defense?
A: It binds to glutathione taking away the cells primary defense mechanism against free
radicals. It also binds to other free radical defense proteins, inactivating them. It damages
the mitochondrial ETC by uncoupling ETC from ATP synthase, thus shutting down FA
oxidation and ATP production, FA build up even more in the liver. It also damages ALDH2,
which increases the levels of free acetaldehyde
34. What is ethanol affect on free radicals?
A: Ethanol induces CYP2E1, which increases likelihood of ROS/RNS generation and the
hydoxyethyl radical may be released as well. Increased free radicals/ROS leads to cellular
damage
35. How does liver cirrhosis affect liver function?
A: Cirrhosis leads to irreversible damage of the liver. The liver becomes enlarged, full of fat,
full of collagen fibers, full of regenerating hepatocytes that are stuck in fibers. This leads to
inability to produce vital proteins and metabolites for body function, thus liver cells die and
liver shrinks. The key loss is the detoxification and conjugation pathways.
36. What are the severe effects of liver damage?
A: Impaired portal vein flow increased portal vein blood pressure capillary burst
bleeding of GITbleed to death due to inability to produce coagulation factors
37. What is a xenobiotic?
A: A chemical or molecule that is foreign to living organisms. Usually connotes a harmful
substance.
38. What are xenobiotics functions?
A: They act at membranes, receptors, DNA, proteins, etc. and change the function of the
biomolecule.
39. What are endogenous toxicants caused by?
A: Inborn errors of metabolism due to gene abnormality
40. What are the phases of detoxification? Describe.
A: Phase I—oxidation, reduction, or hydrolysis carried out by cytochrome P450 mixedfunction oxidases. It prepares compounds for phase II reactions, or can be eliminated
directly as is; Phase II—conjugation with a water-soluble molecule allows for excretion via
blood-kidney-urine or bile-feces
41. What is a consequence of detox?
A: Production of ROS
42. What is the best way support detox?
A: Have a full supply of antioxidant nutrients and factors that support both phases.
43. What are some cofactors that assist in detox? Antioxidants? Conjugates?
A:
 Vitamins B2, 3, 6, 9 and 12, Glutathione, BCAAs, flavonoids, and phospholipids
 Vitamin C, Vitamin E, CoQ10, selenium, zinc, copper, manganese, thiols
 Cysteine, Methionine, Taurine, Glycine, Glutamine, Ornithine, Arginine
LECTURE 36
1. What are cytochrome P450s?
A: There are heme containing proteins with characteristic absorption spectra at 450 nm
when iron is complexed with CO
2. Where are cytochrome P450s located in eukaryotes?
A: Liver rER, Mitochondria, intestinal mucosa
3. What is cytochrome P450 general function?
A: form complex interactions with other protein components for metabolism/detoxification
4. How are cytochrome P450s named?
A: The root for all genomic and cDNA sequences is CYP in humans. Individual families are
named 1-51. Subfamilies are named A-Z. Individual enzymes are numbered consecutively
as they are identified. Ex. CYP1A1, CYP2C19
5. How did super families originate?
A: Exon shuffling, co-expression, frame shifting, alternative splicing, RNA editing, gene
sharing, gene duplication
6. What is responsible for driving expansion and diversification of large multi-gene families?
A: Gene duplication
7. What are the things that all members of the cytochrome P450 superfamily share?
A: A common globular to triangular structural framework that consists of a relatively alphahelix carboxy-terminal half and a relatively beta-sheet rich amino terminal half.
8. What is the general/normal function of P450 enzymes?
A: XenobioticsP450 enzymes with O2, NADPHPolar OH metabolitesDeactivation in
the liverXenobiotic elimination
9. What have cytochrome P450s traditionally been referred to as?
A: Hydroxylases, mixed function oxidases, and monooxygenases
10. What is the main function of cytochrome P450s?
A: Activate molecular oxygen to yield a reactive species that can attack relatively inert
chemical sites in order to introduce hydroxyl groups into structures such as unreactive as
hydrocarbon chains and aromatic rings.
11. What is the catalysis of cytochrome P450 dependent on?
A: Subfamily
12. What induces xenobiotic metabolism by cytochrome P450s?
A: Themselves
13. What xenobiotics appear to induce specific groups of genes?
A:
 Phenobarbital—anti-convulsant, sedative, and hypnotic
 Clofibrate—anti-hyperlipoproteinemic used to treat atherosclerosis
 3-methylcholanthrene—polycyclic aromatic hydrocarbon carcinogen
14. What type of compounds (structure) do cytochrome P450 act on? Why does the structure
matter?
A: Planar; it is important for determining how the compound interacts with cytochrome
P450
15. The detoxification process by P450s can lead to what products? What structure is identified on
ROS that are intermediates of carcinogen detoxification?
A: ROS; epoxides
16. Depending on p450 metabolism, xenobiotic can lead to production of what type of harmful cells?
A: Pre-cancerous cells
17. What is a xenobiotic?
A: A chemical or molecule that is foreign to living organisms that may connote a harmful
substance
18. True or False. Cytochrome P450 covers a broad/diverse spectrum of activities that is dependent
on family and the xenobiotic substrate.
A: True
19. What was the effect of polymorphisms of drug metabolizing enzymes on plasma concentration of
a wild/wild genotype? Wild/variant? Variant/variant?
A: Non-toxic, effective; Toxic, effective; Toxic, non-effective
20. What are the phases of detoxification? Describe.
A: Phase I—oxidation, reduction, or hydrolysis carried out by cytochrome P450 mixedfunction oxidases. It prepares compounds for phase II reactions, or can be eliminated
directly as is; Phase II—conjugation with a water-soluble molecule allows for excretion via
blood-kidney-urine or bile-feces
21. What is a consequence of detox?
A: Production of ROS
22. What happens to the ROS produced during detox?
A: They can leave the liver and lead to damage of the immune, endocrine, and nervous
systems
23. What helps decrease toxin exposure to cells and DNA?
A: Presence of antioxidants
24. What is a carcinogen that was found on peanuts and ears of corn in previous years? Where did it
act in the body?
A: Aflatoxin B1; liver
25. What are the three highest % used CYP in drug metabolism?
A: 2D6 (19%), 3A4, and 3A5 (36%)
26. What is POR? Function?
A: P450 oxidoreductase; hepatic phase I drug metabolism, steroid synthesis/sterol
synthesis, and retinoic acid metabolism
LECTURE 37
1. Humans consume how many g of glucose a day? How much does the blood carry?
A: 160 g; 20 g
2. What percent of glucose is used by the brain?
A: 75%
3. How much (hours) of a supply of glycogen does the liver contain?
A: 12-24 hours
4. Why is glycogen used as a store in addition to TGs?
A:
 Muscle metabolizes glycogen more rapidly that fatty acids
 Fatty acids are no metabolized under anaerobic conditions
 Acetyl CoA (produced by FA break down) cannot be converted to glucose
o Rxn energy of acetyl CoApyruvate is too largely positive
o High acetyl CoA is a negative modulator for PDH
5. Describe the structure and function of structure of glycogen.
A: It is a branched glucose polysaccharide. The glucose units are attached by α-1,4
glycosidic bonds with α-1,6 branches every 8-10 residues. Only one residue has a reducing
end that is attached to glycogenin protein, all other ends are non-reducing. The branched
structure allows for tight packing of glucose, rapid degradation/rapid synthesis, and
enzymes can work on several branches at the same time.
6. Glycogen is a reservoir of glucosyl units for ATP generation from what?
A: Glycolysis
7. What phosphorylates glucose as it enters cells? What phosphorylates glucose as it enters liver
cells? What is the phosphorylated product?
A: Hexokinase; Glucokinase; Glucose 6-phosphate
8. What happens to G6P as it is prepared for attachment to glycogen?
A: It is converted to Glucose 1-Phosphate
9. How is G1P activated?
A: Phosphate on position 1 attaches to α phosphate on UTP displacing PPi, which results in
UDP-glucose (activated glucose)
10. Describe the process of attaching glucose to glycogen.
A: The anomeric carbon of glucose one UDP-glucose forms an α-1,4 linkage with carbon C-4
on the glucose at the non-reducing end of the glycogen chain. This displaces UDP and
increases the glycogen chain length.
11. What happens to chains when the reach ~11 residues long?
A: A 6-8 residue piece is cleaved and reattached to a glucose unit of the glycogen core via α1,6 bond, which forms a branch point
12. How is glucose 6P liberated during glycogen breakdown?
A: It is converted to glucose by glucose 6-phosphatase and released into the blood
13. Glycogen breakdown is tied directly to what other metabolic process?
A: Gluconeogenesis
14. Describe the process of glycogen degradation.
A: Glycogen phosphorylase cleaves a single unit of glucose by transferring a phosphate ion
to the anomeric carbon of the glucose, breaking the α-1,4 glycosidic linkage. G1P is released
and converted to G6P by phosphoglucosemutase. G6P enters a variety of pathways or is
dephosphorylated by glucose 6-phosphatase and transported out of the cell into the blood.
15. What are the two debrancher enzymes that handle branch release from glycogen core? Function?
A: 4:4 transferase—a three glucose unit is removed from the 4 glucoses at the branch point,
and it is attached to the end of the glycogen core by an α-1,4 glycosidic bond; 1,6
glucosidase—single remaining glucose residue of the branch attached by the α-1,6 linkage is
cleaved forming free glucose
16. How is glycogen degraded by lysosomes?
A: Glycogen can be stuck in vesicles that fuse with lysosomes. The lysosomes break down
the glycogen to its subunits (glucose).
17. What is the specific enzyme that hydrolyzes glycogen to glucose?
A: Lysosomal glucosidase
18. What is the cause of type II glycogen storage disease and what are the effects?
A: Genetic defects in lysosomal glucosidase; prevents lysosome from functioning, glycogen
particles build up in vesicles, and heart/liver functions are disrupted
19. Glucagon stimulates what molecule to turn glycogen phosphorylase on and glycogen synthesis
off?
A: PKA
20. What does insulin activate to reverse glucagon effects?
A: Phosphatases
21. During exercise ATPADP, which is converted to AMP by what?
A: Adenylate kinase
22. What does AMP signal?
A: Low levels of glucose in muscles, produce glucose from glycogen stores
23. AMP is an allosteric modulator for what enzyme?
A: Glycogen phosphorylase
24. What are the two major signals that control glycogen phosphorylase activity?
A: AMP—produced by muscle metabolism; Phosphorylation—stimulated by hormone
binding
25. What hormone is activated by high levels of Ca2+? What is its action in the muscles?
A: Calmodulin; It activates PKA, thus activating glycogen phosphorylase
26. In the muscles, how does glycogen get to glycolysis?
A: Glycogen is broken down to G1P by glycogen phosphorylaseconverted to G6P
Skeletal muscle does not have glucose 6-phosphatase so it G6P is sent to glycolytic pathway
to produce ATP within the muscle cell
27. What major hormone turns off glycogen synthesis and keeps glucose in free form for
tissue/muscle utilization?
A: Epinephrine
28. Muscle cells do not have a glucagon receptor. Which of the following stimulate(s) glycogen
breakdown in muscle?
A. AMP
B. epinephrine
C. epinephrine and AMP
D. glucagon
E. insulin
29. If muscles had the enzyme glucose 6-phosphatase to generate free glucose from glucose 6phosphate following muscle glycogen breakdown, this would be a very wasteful process. Why?
A. Glucose would be rephosphorylated by hexokinase, consuming an ATP in the process.
B. This process would compete against glucose being generated by gluconeogenesis in muscle.
C. This process would prevent the muscle cell from using glucose to drive the TCA cycle.
D. This would commit glucose to enter the pentose phosphate pathway.
30. Activating glucose 1-phosphate to UDP-glucose prior to glycogen synthesis…
A. allows glycogen formation to be reversible.
B. ensures that multiple glucose carbons don’t react with the glycogen molecule.
C. increases the reactivity of the glucose molecule.
D. makes glycogen formation irreversible.
E. results from insulin stimulation of the glycogen synthase.
28. C
29. A
30. C
LECTURE 38
1. What pathway is an alternative pathway for G6P utilization?
A: Pentose phosphate pathway
2. What is the main function of the pentose phosphate pathway (PPP)?
A: It is a shunt that generates intermediates of the glycolytic pathway
3. What is the key metabolite of the PPP?
A: NADPH
4. What are the major roles of NADPH?
A: Fatty acid biosynthesis, drug detoxification, GSH defense against ROS
5. What are the two phases of the PPP?
A: Oxidative phase and non-oxidative phase
6. What occurs in the oxidative phase of PPP?
A: G6P is oxidized, NADP+ is reduced. 6-phosphogluconate is decarboxylated forming a 5-C
ribulose derivative and a second NADP+ is reduced.
7. Why is the oxidative phase irreversible?
A: Large negative ΔG values
8. What steps of oxidative pathway are inhibited by NADPH?
A: 1st and 3rd
9. What occurs in the non-oxidative phase of PPP?
A: 5 rearrangement and transfer reactions that are freely reversible and occur in 2 parts.
10. What is part 1 of non-oxidative phase?
A: Two isomerizations of ribulose 5-phosphate
11. What occurs in part 2 of non-oxidative phase?
A: The pentose molecules are converted to intermediates of the glycolytic pathway
(Glyceraldehye 3-phosphate and Fructose 6-Phosphate)
12. Generation of what molecule is used for nucleotide synthesis?
A: Ribose 5-Phosphate
13. True or False. When NADPH levels are low, Phase 1 and 2 are shut down.
A: False. When NADPH levels are normal or high, Phase 1 is shut down and Phase 2 can
operate as needed.
14. What is the key enzyme for NADPH production?
A: Glucose 6-phosphate dehydrogenase
15. What are some uses of NADPH?
A: FA synthesis/chain elongation, Cholesterol synthesis, neurotransmitter synthesis,
nucleotide synthesis
16. How is NADPH used by phagocytic cells?
A: NADPH oxidase uses NADPH to form super oxide from O2 in the mechanism for killing
microorganisms taken up by phagocytic cells
17. How does NADPH help RBC?
A: It helps to maintain GSH in an active form
18. Which enzyme commits glucose to the pentose phosphate pathway?
a. phosphofructose kinase-1
b. hexokinase or glucokinase (depending on the tissue)
c. glucose 6-phosphate dehydrogenase
d. glucose 6-phosphatase
19. Which of the following pathways will be adversely affected by a glucose-6-phosphate
dehydrogenase deficiency?
a. Fatty acid synthesis
b. Cholesterol synthesis
c. Glutathione reduction
d. All the listed pathways would be affected.
18. C
19. D
20. Where does fructose come from? Galactose?
A: Break down of sucrose molecules; breakdown of lactose molecules
21. What is the function of fructose 1-phosphate and galactose 1-P?
A: they are metabolized to intermediates for glucose metabolism
22. Why are none of the sugars considered essential?
A: Our body can synthesize any needed sugar from glucose
23. What are the eight conditionally essential carbohydrates?
A: Mannose, galactose, glucose, fructose, xylose, n-acetylneuraminic acid, nacetylglucosamine, and n-acetylgalactosamine
24. Describe fructose metabolism in the liver.
A: Fructose enters liverphosphorylated at C1 by fructokinase (1 ATP used)F1P cleaved
by aldolase B to dihydroxyacetone and glyceraldehydeglyceraldehyde is phosphorylated
by triose kinase to form G3P (1 ATP used)
25. What is the effect of a defect in aldolase B?
A: Accumulation of F1P
26. How is fructose produced from glucose?
A: Glucose is reduced to sorbitolsorbitol oxidized at C2 to form fructose
27. What do sperm utilize as energy in seminal fluid? In female reproductive tract?
A: Fructose; glucose
28. Describe galactose metabolism.
A: Enters cellphosphorylated at C1 by galactose kinase (1 ATP used)Galactose 1-P
formed Galactose 1-P reacts with UDP glucose to form G1P and UDP-galactoseUDPgalactose converted to UDP-glucose by an epimerase
29. What is the fate of UDP-galactose?
A: used in the synthesis of glycoproteins, glycolipids, and proteoglycans, also forms the milk
sugar lactose in the mammary gland
30. What is the process of glucuronide production from UDP glucose?
A: Oxidation of UDP-glucoseUDP-glucuronatetransfer of glucuronate moiety onto
another compound (protein, sugar, etc.)glucuronate modified to final form (GAG, amino
sugar, etc.)
31. What are fates of glucuronate?
A:
 Increases solubility of molecule to which it is attached.
 Aids in the excretion of non-polar substances (bilirubin, steroids, drugs, drug
products)
32. What are the two types of diseases that result from faulty galactose interconversion?
A: Non-classical galactosemia—galactokinase is deficient and galactose can’t be processed;
classical galactosemia—can’t form UDP-galactose or make molecules dependent on UDPgalactose
33. A male patient who is fructose intolerant due to an Aldolase B deficiency has asked you whether
his sperm cells will be able to obtain the necessary fructose to support motility. You tell him
A. no - because sperm cells are not exposed to dietary fructose.
B. no – because dietary fructose must be processed before delivery to sperm cells.
C. you don’t know offhand, you will have to measure this.
D. yes – because sperm cells can make fructose from glucose as needed.
E. yes – because sperm depend on glucose as the sole energy source.
A: D
LECTURE 39
1. Briefly describe the fed state, fasting state, and starved state.
A: Fed state—glucose available from food, enters blood via gut; Fasting state—liver uses
glycogen store to produce glucose for the body, sends it out to blood. Some glucose made
from precursors; Starved state—liver makes glucose from precursors, sends it out to blood
2. What is gluconeogenesis?
A: Making glucose from precursors
3. How long does glycogenolysis supply glucose?
A: ~18 hours
4. Where does gluconeogenesis primarily occur?
A: Liver
5. The gluconeogenic pathway is largely the reverse of what pathway?
A: Glycolysis
6. What are highly regulated to ensure that either glycolysis or gluconeogenesis predominates?
A: 3 bypass enzymes
7. What are the three primary precursors for gluconeogenesis? Where are they obtained from?
A: Lactate—produced by anaerobic glycolysis in exercising muscle or RBC; glycerol—
produced by adipose tissue following liberation of fatty acids; amino acids—obtained by
degradation of protein, especially muscle.
8. What is the main amino acid used?
A: Alanine
9. What TCA intermediate do lactate and alanine form? How?
A: Pyruvate; LDH oxidizes lactate to pyruvate using NAD+ to NADH; Alanine
aminotransferase converts alanine to pyruvate
10. What gluconeogenesis precursor is converted to dihydroxyacetone phosphate (DHAP)?
A: Glycerol
11. What is the first bypass step in gluconeogenesis? What enzyme is bypassed?
A: Pyruvate conversion to PEP; pyruvate kinase
12. What is the process of the pyruvate conversion to PEP?
A: Pyruvate uses ATP to add CO2 to form OAA by pyruvate carboxylase (in
mitochondria)OAA can’t cross the inner mito mem so utilizes the OAA/asp or OAA/mal
shuttleOAA released outside of the mitochondiraOAA converted back to PEP by use of
GTP and CO2 release
13. How is PEP converted to Fructose 1,6-bisP? Where does this occur?
A: PEP is hydrolyzed to 2-phosphoglycerate (PGA)2-PGA is isomerized to 3-PGA3-PGA
is phosphorylated to 1,3-BPG1,3-BPG is reduced and dephosphorylated to glyceraldehyde
3-Pglyceraldehydes 3-P isomerize to form DHAPGlyceraldehyde 3-P and DHAP join to
form fructose 1,6-bisP; occurs in cytoplasm
14. What is the second bypass step in gluconeogenesis? What enzyme is bypassed?
A: Fructose 1,6-bisP to Fructose 6-P; PFK-1
15. How does fructose 1,6-bisP convert to fructose 6-P?
A: Dephosphorylation by fructose 1,6-bisphosphatase
16. What is the third bypass step in gluconeogenesis? What enzyme is bypassed?
A: Glucose 6-P to glucose; glucokinase
17. How does glucose 6-P convert to glucose?
A: Dephosphorylation by glucose-6-phosphatase
18. Where does the energy requirement for gluconeogenesis come from?
A: Beta-oxidation of fatty acids
19. How many moles of high energy phosphate bonds are used during gluconeogenesis? Where are
they used?
A: 6; 2 moles ATP used as 2 moles Py are carboxylated (1st bypass); 2 moles OAA converted
to 2 moles of PEP require 2 moles GTP; 2 moles ATP used to phosphorylate 2 moles of 3-PGA
20. What is the function of PFK-1?
A: Commit glucose to glycolysis
21. In glycolysis, which pathway is inhibited by high-energy charge? Which is stimulated by highenergy charge?
A: Catabolic; Anabolic
22. What is the normal range of adenylate charge? What happens below? Above?
A: 0.8 to 0.95; Catabolic is dominant; anabolic is dominant
23. What molecule(s) activate PFK-1? Inhibit?
A: AMP and Fructose 2,6-bisP; ATP
24. What stimulates glycogenolysis?
A: Glucagon
25. What conditions cause gluconeogenesis?
A: Fasting, prolonged exercise, high-protein diet, and conditions of stress
26. What are the two regulators of gluconeogenesis?
A: Availability of substrate (glycerol, lactate, AA) and activity/amount of key enzymes
27. What is a negative modulator of PDH?
A: High acetyl CoA levels
28. What prevents futile cycling of PEP and pyruvate?
A: Glucagon stimulating phosphorylation of PK to an inactive form
29. How does fasting state push the second bypass toward f-6-p?
A: low levels of AMP and fructose 2,6-bisP meaning low PFK-1 activity
30. What happens in the second bypass during the fed state?
A: AMP and Fructose 2,6-bisP activate PFK1 and allosterically inhibit fructose 1,6bisphosphatase activity, therefore this activity is decreased during glycolysis.
31. What is the key PFK-1 activator in liver and adipose tissue?
A: Fructose 2,6-bisP (signals need to increase glycolysis)
32. How is fructose 2,6-bisP a bifunctional enzyme?
A: When dephosphorylated, it is activated for production from fructose 6-P, but when
phosphorylated, it is activated to produce f-6-P (see below)
33. Glucokinase is (very active/not very active) during conditions that support gluconeogenesis?
A: Not very active
*****REVIEW LECTURE 40 ON LIPID NUTRITION!!!!
LECTURE 41
1. What are some diseases resulting from deficiency/imbalance in lipids?
A: Atherosclerosis and obesity
2. What are components of dietary lipids?
A: triglycerides, phospholipids, cholesterol, cholesterol esters, and fat-soluble vitamins
3. What are the fat-soluble vitamins?
A: A, D, E, K
4. What are bile salts?
A: Amphipathic molecules that emulsify dietary TGs and other lipids into micelles
5. What would happen if bile salts weren’t present?
A: Fats would clump together to minimize water contact, form large droplets, and clog
things up
6. What is cholic acid?
A: it is the major bile salt in humans. It is derived from cholesterol and combines with
taurine or glycine to form taurocholic and glycocholilic acids
7. What increases the polar, soluble character of bile salts?
A: Conjugation and deprotonating
8. What is another name for bile salts?
A: Detergent
9. Where are bile salts synthesized and where are they stored?
A: Liver; gall bladder
10. What is pancreatic lipase and how does it function?
A: It is a water soluble enzyme produced by the pancreas that removes fatty acids from TGs.
It uses a colipase (cofactor) to bind to emulsified TGs at the lipid-water interface. Hydrolysis
produces 2 free FAs and a 2-monoacylglycerol.
11. What form of cholesterol is more common in the diet than free cholesterol?
A: Esterified
12. What does the pancreas produce to hydrolyze the ester bond, which produces a free cholesterol
and free acyl compound?
A: Cholesterol esterase
13. Why does cholesterol esterase hydrolyze esterified cholesterol?
A: Because free cholesterol is easier to transport from the intestinal lumen into the
intestinal epithelium
14. What hydrolyzes dietary phospholipids into lysophospholipid and a free FA?
A: Pancreatic phospholipase A2
15. What is the function of lysophospholipid?
A: It is a powerful detergent that aids in the emulsifying action of bile salts
16. Describe the role of bile salts in lipid uptake.
A: Bile salts present lipid products to small intestine luminal membrane as mixed micelles
Mixed micelles are absorbed into cells and the bile salts are releasedbile salt conjugates
are broken down by bacterial processes in the gutbile salts are separately reabsorbed in
lower small intestine and sent via the blood back to the liver
17. How are triglycerides resynthesized in the intestinal epithelial cell?
A: Once the micelle is absorbed into the intestinal cell2 free FA are activated by acetyl
CoAonce activated each FA is added to 2-monoacylglycerol to form TGpackaged with
other lipids and apoprotein to form Nascent chylomicron
18. What does nascent mean?
A: New
19. What are chylomicrons? What do they contain?
A: They are collections of phospholipids that form a shell with a hydrophobic interior and a
polar exterior; They contain TGs within the shell, cholesterol, cholesterol esters, fat soluble
vitamins, and proteins on the surface
20. What is the largest component of chylomicrons?
A: TGs
21. What dictates function and recognition of chylomicron?
A: Surface proteins
22. What are the key differences between intestinal epithelium cells and liver/adipose cells
regarding TGs and PLs?
A: Intestinal cells use 2 monoacylglycerol as starting material for resynthesizing TGs and
contain ApoB-48 (chylomicrons); Liver/adipose tissue use phosphatidic acid as starting
material to synthesize new PLs and contain ApoB-100 (VLDLs)
23. What is the major apoprotein associated with chylomicrons?
A: ApoB-48
24. Why do chylomicrons use ApoB-48?
A: The TGs are resynthesized in the smooth ER and incorporated into the lipoprotein and
ApoB-48 is made in the rough ER. ApoB-48 is combined with lipoprotein by intestinal cell
golgi to finalize nascent chylomicron synthesis.
25. What transfers lipid and TG across ER membrane and into the ApoB particle as it is made in the
ER lumen?
A: Microsomal triglyceride transfer protein (MTP)
26. What disease state has missing MTP? What symptoms do these patients suffer?
A: Abetalipoproteninemia which chylomicrons and VLDLs aren’t formed; symptoms include
lipid malabsorption, which results in fatty feces (steatorrhea) and vomiting
27. What is Apoprotein E function?
A: It is recognized by membrane receptors (especially liver cells) and facilitates chylomicron
entry into cells by endocytosis
28. What is Apoprotein CII function?
A: it is the activator of lipoprotein lipase (LPL)
29. What is LPL and what is its function?
A: It is located on the surface of capillary endothelial cells and it digests TGs from
chylomicrons for cells
30. What stimulates LPL production and secretion?
A: Insulin
31. What do chylomicrons do in the blood?
A: They interact with HDL and transfer ApoE and ApoCII
32. What is the fate of chylomicrons?
A: LPL digests TGs of chylomicronsFAs produced by LPL enter cells and used for energy
or associate with albumin to increase solubilityportion of chylomicron left over after LPL
is called chylomicron remnant, which is taken up by liver cells and recycled after lysosomal
digestion
33. What do chylomicron remnants use to bind to receptors on hepatocytes?
A: ApoE
34. What is the function of bile salts in digestion of dietary lipid?
a. They act as detergents that emulsify dietary lipid in the small intestine.
b. They activate the pancreatic enzymes that digest lipid molecules.
c. They aid in the uptake of chylomicrons by instestinal epithelial cells.
d. Their presence distinquishes chylomicrons from VLDLs.
35. Steatorrhea (fatty stools) results from malabsorption of dietary fats. Which of the following
could cause this?
a. Lack of bile salts in the digestive tract.
b. Lack of sufficient water in the digestive tract.
c. The presence of cholesterol in the digestive tract.
d. The presence of triacylglcerols and 2-monoacylglycerols in the digestive tract.
36. Muscle and adipose cells have lipoprotein lipase (LPL) on their exterior surface. Why does
muscle LPL have a smaller Km than adipose LPL?
a. So that liver can utilize chylomicrons even at very low concentrations.
b. So that muscle can utilize chylomicrons preferentially compared to adipose tissue.
c. The lower Km indicates LPL has a higher affinity for ApoB-48 binding.
d. The lower Km indicates that adipose LPL has a lower affinity for cholesterol
34. A
35. A
36. B