1. Metabolism – questions and answers
Phase 2 MBChB
Gastroenterology system block
Gerhard H. W. May

2. Which one is FALSE about lipids?
Triglycerides are the main storage form of lipids in the human body
Some lipids contain phosphate groups, carbohydrates, or proteins
Fatty acids can be used for gluconeogenesis
Lipids are mostly hydrocarbon and water-insoluble
Lipid absorption is required for the absorption of some vitamins
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3. Which one is FALSE about fat catabolism?
The first step of fat catabolism is lipolysis
Fatty acids first have to be activated to acetyl-CoA
Activation occurs in the cytoplasm
The pathway for breakdown of fatty acids is termed beta oxidation
Beta oxidation occurs in the mitochondrial matrix
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4. Lipid metabolism - overview
dietary fat
stored fat
triglyceride
fatty acyl-carnitine
fatty acyl-carnitine
lipolysis
fatty acyl-CoA
fatty acids
glycerol
activation
fatty acyl-CoA
b oxidation
fatty acid synthesis
malonyl-CoA
acetyl-CoA
citrate cycle
acetyl-CoA
citrate
citrate
glycolysis
glycolysis
dietary carbohydrates
Mitochondrion
Cytoplasm
Membrane

5. Which one is FALSE about ketone bodies?
They are formed in the liver from acetyl-CoA
They diffuse into the blood stream
They are toxic to peripheral tissues which prefer glucose
They accumulate as a by-product of beta oxidation under conditions of extreme starvation
They can lead to ketoacidosis
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6. Ketone bodies Formed in liver mitochondria
from acetyl-CoA from b oxidation
Diffuse into the blood stream and to peripheral tissues
Important molecules of energy metabolism for heart muscle and renal cortex
converted back to acetyl-CoA, which enters TCA cycle

7. How often does beta oxidation happen for the breakdown of a C14 fatty acid?
Four times
Five times
Six times
Seven times
Eight times
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8. What are the products of the breakdown of a C14 fatty acid?
8 acetyl-CoA, 7 NADH + H+, 7 FADH2
7 acetyl-CoA, 6 NADH + H+, 6 FADH2
7 acetyl-CoA, 6 NADPH + H+, 6 FADH2
7 acetyl-CoA, 6 NADH + H+, 6 FADH2, 6 GTP
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9. b oxidation Cycle of reactions Four steps in each cycle
Acyl-carnitine
b oxidation
Cycle of reactions
in mitochondrial matrix
Four steps in each cycle
Products of each cycle:
1 acetyl-CoA
1 FADH2
1 NADH + H+
1 fatty acyl-CoA, shortened by 2 carbon atoms
TCA cycle

10. Which one is FALSE about amino acid catabolism?
The amino group of amino acids is removed to form urea
Removal of the amino group only occurs in liver cells
Carbon skeletons of all amino acids can enter the TCA cycle
Glucogenic amino acids can be used to form glucose
Ketogenic amino acids can be completely oxidised in the TCA cycle
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11. Which one is FALSE about the removal of nitrogen?
Amino groups from amino acids are directly transferred to carbamoylphosphate
One nitrogen of urea is derived from aspartate
One nitrogen of urea is derived from free ammonium
Free ammonium is toxic
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12. The urea cycle Urea is synthesised in a complex series of reactions
in the liver
urea/ornithine cycle
one nitrogen from free ammonium, the other from aspartic acid
carbon from CO2

13. Which one is FALSE about fatty acid synthesis?
It is a reductive process
It occurs in the cytoplasm
Citrate transports acetyl groups from mitochondria to the cytoplasm
It requires NADPH
Fatty acid synthase consists of 7 distinct peptides
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14. Fatty acid synthesis vs. degradation
location
cytoplasm
mitochondrial matrix
intermediates
linked to ACP
linked to CoA
enzymes
single polypeptide
separate
cofactors
NADPH (reductant)
NAD+, FAD (oxidants)
length constraints
stops at C-16
no constraints

15. The donor molecule of carbon atoms to a growing fatty acid is...
Acetyl-CoA
Malonyl-CoA
Citrate
Acyl-CoA
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16. Acetyl-CoA carboxylase - regulation
Insulin signals the fed state:
stimulates storage of fuels and synthesis of proteins
Glucagon signals starved state, epinephrine signals requirement for energy:
mobilise glycogen stores
Citrate stimulates allosterically:
citrate levels are high when acetyl-CoA and ATP are abundant
Antagonised by palmitoyl CoA:
abundant when fatty acids are in excess

17. What is NOT the meaning of ‘citrate stimulates allosterically’?
Citrate binds to a site separate from the catalytic cleft of acetyl-CoA carboxylase
Citrate helps insulin to stimulate the catalytic activity of acetyl-CoA carboxylase
When there is lots of citrate it activates acetyl-CoA carboxylase
Binding of citrate to acetyl-CoA carboxylase activates the catalytic activity of the enzyme
Individual acetyl-CoA carboxylase enzyme molecules can be affected by a number of small molecule effectors, citrate is one of them
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18. Which one is FALSE about glycogen and its synthesis?
Liver glycogen can serve as a source for blood glucose
Muscle glycogen can only be used for energy generation in the muscle cell
Glucose has to be bound to UDP before it can be transferred onto glycogen
Glycogen synthase can not introduce branches
Glycogen synthase starts new glycogen molecules by binding one glucose molecule to a glycogenin protein
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19. What is glycogenin? Glycogen Glycogenin protein
Glycogenin is a protein and sits at the centre of a glycogen polymer
It has catalytic activity and can covalently bind up to four glucose molecules to itself, essentially forming the starting point of the glycogen polymer
This is important because glycogen synthase can only add glucose residues to an existing glycogen chain

20. Which one is FALSE about glycogen breakdown?
Glucose is removed from glycogen as glucose-6-P
Liver cells can create free glucose from glycogen
Glucagon inhibits glycogen synthesis and stimulates glycogen breakdown
Insulin inhibits glycogen breakdown and stimulates glycogen synthesis
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21. Glycogen breakdown summary
Rate limiting step
glycogen phosphorylase
glucose-1-phosphate
phosphoglucomutase
glucose-6-phosphate
In liver only
glucose-6-phosphatase
glucose-6-phosphatase
glucose
glycolysis
Blood via GLUT2
transporter

22. Which one is FALSE about gluconeogenesis?
It is a pathway for the synthesis of new glucose from non-carbohydrate precursors
Lactate, glycerol, and glucogenic amino acids are precursors for gluconeogenesis
It is glycolysis run in reverse
It occurs mainly in the liver
It is a very energy-consuming process
Glucagon stimulates it, insulin inhibits it
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23. Gluconeogenesis the TCA cycle intermediate which accepts acetyl groups
Requires four unique liver enzymes
Proceeds via the synthesis of oxaloacetate in mitochondria
the TCA cycle intermediate which accepts acetyl groups
important for accepting acetyl groups from fat breakdown
Energy consuming

24. Amino acids are oxidised in the TCA cycle

25. Amino acids as precursors for gluconeogenesis

26. Which one is FALSE about metabolism?
Catabolic pathways break down reduced substrates for energy generation
Anabolic pathways synthesise oxidised products from small, reduced precursors
Anabolic pathways require the input of energy in the form of ATP
Anabolic pathways require the input of reducing force in the form of NADPH
Catabolic pathways generate reduced cofactors which can drive oxidative phosphorylation 10

27. ATP as energy currency

28. Metabolism - redox reactions
ADP + Pi
ATP
Reduced biosynthetic
products
ANABOLISM
Oxidised precursors
NADP+
NADPH + H+
Reduced fuel
CATABOLISM
Oxidised products
NAD+
(FAD)
NADH + H+
(FADH2)
OXIDATIVE
PHOSPHORYLATION
H2O O2
ATP
ADP + Pi

29. Which one is FALSE about glycolysis?
It generates 2 ATP molecules per glucose molecule broken down
It forms the first stage of carbohydrate catabolism
It occurs in the mitochondrial matrix
It generates two NADH + H+ per glucose molecule broken down 10

30. Glycolysis Stage 1: glucose is trapped and destabilised
Stage 2: two interconvertible three-carbon molecules are formed
Stage 3: generation of ATP

31. Pyruvate... Directly enters oxidative phosphorylation
Is converted to oxaloacetate and is used for fatty acid degradation
Is converted to acetyl-CoA and then enters the TCA cycle 10

32. Which one is FALSE about the TCA cycle?
It provides precursors for gluconeogenesis
Breakdown products from carbohydrate, fat and protein metabolism feed into it
It consumes NADH and FADH2
Carbon skeletons of amino acids enter it at different points
It occurs in the mitochondrial matrix 10

33. The TCA cycle - overview
Eight reactions in total
A two-carbon unit (from acetyl-CoA) condenses with a four-carbon unit
The resulting six-carbon unit is decarboxylated twice
yields CO2
Four oxidation reactions
yield NADH + H+ and FADH2
One GTP is formed
energy
The four-carbon unit is recreated

34. Which one is FALSE about oxidative phosphorylation?
Electrons from NADH and FADH2 are transferred onto O2
The electron transport chain is located in the inner mitochondrial membrane
Protons are pumped from the intermembrane space to the mitochondrial matrix
Protons flow back across the membrane, following their concentration gradient
Proton flow is coupled to ATP synthesis
Oxidative phosphorylation consists of two separate proton pump systems
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35. Essence of oxidative phosphorylation
Electrons from NADH and FADH2 are used to reduce O2 to H2O
Their energy is used to pump protons (H+) from the mitochondrial matrix to the intermembrane space
pH decreases in intermembrane space, increases in the matrix
Protons flow back across the membrane, following their concentration gradient
Energy of proton flow is used to phosphorylate ADP to ATP

36. Electron transport and H+ pump
NADH donates electrons to complex I
FADH2 donates electrons to complex II
Complexes I, III and IV pump H+ out while transporting electrons
Electrons are finally transferred onto O2

37. The P/O ratio...
Is a measure of the number of ATP molecules formed per oxygen atom reduced
For NADPH is 2.5
Measures the ratio between NADPH and NADH in the cell
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38. Which of the following is FALSE about redox potentials?
The redox potential of a molecule is a measure of its likelihood to loose an electron
The more negative a molecule’s redox potential, the more likely it is to donate an electron
Electrons can be transferred from molecules with negative redox potentials to those with more positive redox potentials
The difference in redox potentials between substrate and product of a redox reaction relates to the free energy change of the reaction
NADH has a more negative redox potential than FADH2, therefore transfer of its electrons to oxygen releases less energy
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39. Redox potentials
The standard redox potential E’o of a (reduced) substance X is a measure for how readily X donates an electron (in comparison with H2)
X-  X + e-
A negative E’o means that the reduced form of X has a lower affinity for electrons than H2, a positive E’o means the opposite

40. Some standard redox potentials
NADH + H+ ‘likes’ to donate electrons more than those molecules below it

41. Some standard redox potentials
FADH2 has a lower redox potential

42. Some standard redox potentials
Molecules of the electron transport chain have even lower redox potentials

43. Some standard redox potentials
Molecular oxygen has the lowest redox potential in this table and is most likely to accept electrons

44. How are redox potentials related to ATP?
Electrons are handed from NADH (or FADH2) to molecules of lower redox potential, like a relay baton
Redox potentials:
NAD+/NADH V
½ O2/H2O V
Transferring electrons from a negative to a positive redox potential releases energy
½ O2 + NADH + H+  H2O + NAD+
Go’ = kJ/mol
Oxidative phosphorylation converts the energy inherent in these electrons into chemical energy in the form of ATP
Difference: 1.14 V
For FADH2: 1.04 V