Unit 10 Question Bank
Format note: the TMU Biochemistry paper gives five suggested
answers (A–E), not four — these MCQs match that. Items tagged TMU 2019 or
TMU 2020/21 come from the real papers. Answers are verified against Harper's
Illustrated Biochemistry; the "marking schemes" in the source folder are other students'
answer sheets, not official, so they are never used as the authority.
0 / 25 answered
1Which one of the following statements concerning glycolysis is correct?
Answer: A
This stem is from the 2020/21 paper, Section IV. The key distinction is hexokinase versus glucokinase: in liver, glucokinase — with its much higher Km — is what handles glucose after a meal. Conversion of glucose to lactate is precisely what does not require oxygen; glycolysis is cytosolic; the net yield is 2; and pyruvate kinase is irreversible.TMU 2020/21 paper Section IV Q2 · Harper's ch.17, pp.170–172
2Glycolysis is best defined as ( ).
Answer: B
⭐ Set as a Section I definition in the 2019 paper. The answer sheet's wording is “the major initial pathway for glucose metabolism, occurs in the cytosol of all cells”. It is unique in functioning either aerobically or anaerobically. Option C is gluconeogenesis, option D glycogenolysis, option E the pentose phosphate pathway.Harper's ch.17, p.168 · TMU 2019 paper Section I
3Erythrocytes metabolise glucose entirely to lactate even in the presence of oxygen because ( ).
Answer: C
Glycolysis in erythrocytes always terminates in lactate, because the subsequent reactions of pyruvate oxidation are mitochondrial and erythrocytes lack mitochondria. This is also why a glycolytic enzyme defect presents as haemolytic anaemia — glycolysis is the red cell's only source of ATP.Harper's ch.17, pp.168, 171
4Heart muscle survives ischaemia poorly because ( ).
Answer: D
Skeletal muscle can fall back on anaerobic glycolysis and survive anoxic episodes; heart muscle, adapted for aerobic performance, has relatively low glycolytic activity and poor survival under ischaemia. One line of biochemistry explaining the clinical difference between a cramp and an infarct.Harper's ch.17, p.168 · TMU Lecture 11 Slide 4
5Which enzyme is the MAJOR site of regulation of glycolysis?
Answer: E
Three reactions of glycolysis are markedly exergonic and physiologically irreversible — those catalysed by hexokinase (and glucokinase), phosphofructokinase and pyruvate kinase — and these are the major sites of regulation. PFK-1 is the principal one.Harper's ch.17, p.172
6Phosphofructokinase is significantly inhibited at normal intracellular ATP concentrations. This inhibition is rapidly relieved by ( ).
Answer: A
Holding the enzyme partly switched off all the time gives it somewhere to go. 5′AMP rises steeply when ATP falls — because the AMP pool is small (Unit 8's adenylate kinase) — so it is a far more sensitive alarm than ATP is a gauge. The most important regulatory enzyme in glycolysis listens to the most sensitive available signal.Harper's ch.17, p.172
7Compared with hexokinase, glucokinase ( ).
Answer: B
Hexokinase has a high affinity (low Km) and is saturated even at low blood glucose. Glucokinase's much higher Km means it acts only when glucose is high — after a meal. Its two jobs: in liver, to remove glucose from the blood, providing G6P in excess of glycolytic requirements for glycogen synthesis and lipogenesis; in pancreas, to signal glucose availability and lead to insulin secretion.Harper's ch.17, p.170 · TMU Lecture 11 Slide 11
8Which enzyme cleaves fructose 1,6-bisphosphate into two triose phosphates?
Answer: C
Aldolase splits the six-carbon sugar into glyceraldehyde 3-phosphate and dihydroxyacetone phosphate. Phosphotriose isomerase then interconverts them, so that BOTH halves continue down the pathway — which is why the payoff phase runs twice per glucose.Harper's ch.17, p.170
9The only oxidation step in glycolysis is catalysed by ( ).
Answer: D
It converts glyceraldehyde 3-phosphate to 1,3-bisphosphoglycerate, reducing NAD⁺ to NADH. Because this step consumes NAD⁺ from a small pool, NAD⁺ must be continuously regenerated — which is the entire reason lactate is formed anaerobically.Harper's ch.17, p.171
10Which two enzymes of glycolysis generate ATP by substrate-level phosphorylation?
Answer: E
And Unit 8's free-energy table predicted exactly this: 1,3-bisphosphoglycerate (−49.3) and phosphoenolpyruvate (−61.9) are the only glycolytic intermediates above ATP (−30.5). A compound below ATP has no capacity to phosphorylate ADP — so these had to be the two steps.Harper's ch.17, p.171 · Harper's ch.11, Table 11–1
11The toxicity of arsenic in glycolysis is due to arsenate ( ).
Answer: A
At the glyceraldehyde-3-phosphate dehydrogenase step, arsenate gives 1-arseno-3-phosphoglycerate, which undergoes spontaneous hydrolysis to 3-phosphoglycerate without forming ATP. An elegant poison: it does not block the pathway, it uncouples it — the pathway keeps running but stops paying. (Arsenite, separately, inhibits PDH via lipoic acid.)Harper's ch.17, p.171
12Blood samples for glucose measurement are collected into tubes containing fluoride because fluoride inhibits ( ).
Answer: B
Enolase is inhibited by fluoride — which stops the erythrocytes in the tube from consuming the glucose you are trying to measure. Enolase also requires Mg²⁺ or Mn²⁺. A laboratory practice with a biochemical reason, and a favourite MCQ.Harper's ch.17, p.171
13The pyruvate kinase reaction is essentially irreversible partly because ( ).
Answer: C
Two reasons. Partly the large free-energy change — PEP is the most energetic phosphate in the table. And partly this one: the cell makes the step one-way by immediately converting the product into something else, the same device as hydrolysing PPi in Unit 8.Harper's ch.17, p.171
14Under anaerobic conditions pyruvate is reduced to lactate. The PURPOSE of this reaction is to ( ).
Answer: D
Lactate is not a waste product; it is the price of a recycled coenzyme. Harper's: “the reoxidation of NADH via lactate formation allows glycolysis to proceed in the absence of oxygen by regenerating sufficient NAD⁺ for another cycle of the reaction catalysed by glyceraldehyde-3-phosphate dehydrogenase.”Harper's ch.17, p.171 · TMU Lecture 11 Slide 24
15The increased oxygen consumption seen after vigorous exercise — the oxygen debt — is largely due to ( ).
Answer: E
When lactate production is high — vigorous exercise, septic shock, cancer cachexia — much is used in the liver for gluconeogenesis, an energy-expensive process. The resulting rise in oxidation of metabolic fuels to supply that ATP and GTP is seen as the oxygen debt. You keep breathing hard because your liver is busy.Harper's ch.17, p.172
16The 2,3-bisphosphoglycerate pathway in erythrocytes bypasses which enzyme?
Answer: A
The bypass effectively dissipates as heat the free energy associated with the high-energy phosphate of 1,3-bisphosphoglycerate — so no ATP is made at that step. The erythrocyte sacrifices an ATP to manufacture 2,3-BPG, which stabilises the T state of haemoglobin and improves oxygen delivery (Unit 4). It is a cell whose job is oxygen transport, not ATP.Harper's ch.17, p.172 · TMU Lecture 11 Slide 30
17The pyruvate dehydrogenase complex contains three catalytic enzymes and requires how many cofactors?
Answer: B
Three enzymes — pyruvate dehydrogenase, dihydrolipoamide transacetylase, dihydrolipoamide dehydrogenase — and five cofactors. Note that four of them derive from B vitamins: thiamin (TPP), riboflavin (FAD), niacin (NAD⁺) and pantothenic acid (CoA). That is why thiamin deficiency causes lactic acidosis.TMU Lecture 11 Slide 31 · Harper's ch.17, p.173
18The oxidation of pyruvate to acetyl-CoA is ( ).
Answer: C
It is the irreversible route from glycolysis to the citric acid cycle. Once carbon becomes acetyl-CoA it can never return to pyruvate — which is precisely why fat cannot be converted to glucose, and why prolonged starvation must consume muscle protein instead.TMU Lecture 11 Slide 31 · Harper's ch.17, p.173
19Pyruvate dehydrogenase is inhibited by end-product inhibition by ( ).
Answer: D
Its own products. PDH is also regulated by covalent modification — phosphorylation of three serine residues by a kinase decreases activity, dephosphorylation by a phosphatase increases it. The dephosphorylated form (PDH-a) is active.Harper's ch.17, p.174 · TMU Lecture 11 Slide 33
20The PDH kinase — which switches the enzyme off — is activated by increases in ( ).
Answer: E
Read those three ratios: every one signals that the cell has plenty of energy. Note the corollary — PDH is inhibited not only by a high energy potential but also when fatty acids are being oxidised, since that raises acetyl-CoA and NADH.Harper's ch.17, p.174 · TMU Lecture 11 Slide 33
21In starvation, pyruvate dehydrogenase activity falls. The physiological benefit is ( ).
Answer: A
Rising free fatty acids raise acetyl-CoA and NADH, decreasing the proportion of PDH in the active form and leading to a sparing of carbohydrate. Because PDH is the irreversible gate out of glycolysis, shutting it preserves glucose for the brain, which cannot use fatty acids. Conversely, in adipose tissue the enzyme is activated by insulin, where glucose supplies acetyl-CoA for lipogenesis.Harper's ch.17, p.174 · TMU Lecture 11 Slide 34
22Arsenite and mercuric ions inhibit pyruvate dehydrogenase by reacting with ( ).
Answer: B
Allowing pyruvate to accumulate. The same happens with dietary thiamin deficiency, since PDH requires TPP. Many alcoholics are thiamin deficient — poor diet plus alcohol inhibiting thiamin absorption — and may develop potentially fatal pyruvic and lactic acidosis.Harper's ch.17, p.174
23Inherited deficiency of aldolase A or of erythrocyte pyruvate kinase causes ( ).
Answer: C
Harper's states the general pattern: diseases in which glycolytic enzymes are deficient are seen mainly as haemolytic anaemias, or as fatigue if the defect affects skeletal muscle. The erythrocyte has no mitochondria, so glycolysis is its only ATP source — a defect leaves it unable to maintain its membrane. Muscle phosphofructokinase deficiency instead causes low exercise capacity, particularly on high-carbohydrate diets.Harper's ch.17, p.174
24The complete oxidation of one molecule of glucose under aerobic conditions yields approximately ( ).
Answer: D
Up to 32 mol ATP aerobically, but only 2 mol when oxygen is absent. Most is formed by oxidative phosphorylation from reoxidation of the reduced coenzymes; the remainder by substrate-level phosphorylation.
Note that 32 is only arithmetically possible with P:O = 2.5 and 1.5 — the older 3/2 values would give 38. Your Lecture 11 slide 36 says 32, as does Harper's. See Unit 9 §7.TMU Lecture 11 Slide 36 · Harper's ch.17
Note that 32 is only arithmetically possible with P:O = 2.5 and 1.5 — the older 3/2 values would give 38. Your Lecture 11 slide 36 says 32, as does Harper's. See Unit 9 §7.TMU Lecture 11 Slide 36 · Harper's ch.17
25In fast-growing cancer cells, glycolysis proceeds faster than the citric acid cycle requires. The consequence is ( ).
Answer: E
Large amounts of pyruvate are reduced to lactate and exported, producing a relatively acidic local environment which may have implications for cancer therapy. That lactate is then used for gluconeogenesis in the liver — an energy-expensive process responsible for much of the hypermetabolism seen in cancer cachexia. The patient's liver spends ATP recycling the tumour's waste.Harper's ch.17, p.172 · TMU Lecture 11 Slide 5
1 Glycolysis — 3′ · ⭐ SET IN THE 2019 PAPER+
The major pathway for glucose metabolism, which occurs in the cytosol of all cells.
It converts glucose to pyruvate aerobically or lactate anaerobically, and is unique in that it can function either aerobically or anaerobically. The overall anaerobic equation is glucose + 2 ADP + 2 Pi → 2 lactate + 2 ATP + 2 H₂O.
It is regulated at three markedly exergonic, physiologically irreversible steps, catalysed by hexokinase (and glucokinase), phosphofructokinase and pyruvate kinase. It is also the main pathway for the metabolism of fructose, galactose and other dietary carbohydrates.Harper's ch.17, p.168
It converts glucose to pyruvate aerobically or lactate anaerobically, and is unique in that it can function either aerobically or anaerobically. The overall anaerobic equation is glucose + 2 ADP + 2 Pi → 2 lactate + 2 ATP + 2 H₂O.
It is regulated at three markedly exergonic, physiologically irreversible steps, catalysed by hexokinase (and glucokinase), phosphofructokinase and pyruvate kinase. It is also the main pathway for the metabolism of fructose, galactose and other dietary carbohydrates.Harper's ch.17, p.168
2 Hexokinase and glucokinase — 3′+
Both phosphorylate glucose to glucose 6-phosphate using ATP, but differ in Km and in distribution.
Hexokinase is present in most tissues and has a high affinity (low Km) for glucose, so it is saturated and active even at low blood glucose — every tissue gets its glucose.
Glucokinase is found in liver and pancreatic β islet cells and has a much higher Km, so it acts only when glucose is high. In the liver its function is to remove glucose from the blood following a meal, providing glucose 6-phosphate in excess of glycolytic requirements for glycogen synthesis and lipogenesis; in the pancreas, the glucose 6-phosphate it forms signals increased glucose availability and leads to the secretion of insulin.Harper's ch.17, p.170
Hexokinase is present in most tissues and has a high affinity (low Km) for glucose, so it is saturated and active even at low blood glucose — every tissue gets its glucose.
Glucokinase is found in liver and pancreatic β islet cells and has a much higher Km, so it acts only when glucose is high. In the liver its function is to remove glucose from the blood following a meal, providing glucose 6-phosphate in excess of glycolytic requirements for glycogen synthesis and lipogenesis; in the pancreas, the glucose 6-phosphate it forms signals increased glucose availability and leads to the secretion of insulin.Harper's ch.17, p.170
3 The pyruvate dehydrogenase complex — 3′+
The multienzyme complex catalysing the oxidative decarboxylation of pyruvate to acetyl-CoA — the irreversible route from glycolysis to the citric acid cycle.
It contains three catalytic enzymes: pyruvate dehydrogenase (PDH), dihydrolipoamide transacetylase and dihydrolipoamide dehydrogenase; and requires five cofactors: TPP, lipoic acid, NAD⁺, FAD and CoASH.
It is regulated by end-product inhibition (by acetyl-CoA and NADH) and by covalent modification — phosphorylation of three serine residues decreasing activity, dephosphorylation increasing it.TMU Lecture 11 Slide 31 · Harper's ch.17, p.173
It contains three catalytic enzymes: pyruvate dehydrogenase (PDH), dihydrolipoamide transacetylase and dihydrolipoamide dehydrogenase; and requires five cofactors: TPP, lipoic acid, NAD⁺, FAD and CoASH.
It is regulated by end-product inhibition (by acetyl-CoA and NADH) and by covalent modification — phosphorylation of three serine residues decreasing activity, dephosphorylation increasing it.TMU Lecture 11 Slide 31 · Harper's ch.17, p.173
4 Oxygen debt — 2′+
The increase in oxygen consumption seen after vigorous exercise.
It results from the increased oxidation of metabolic fuels needed to provide the ATP and GTP for hepatic gluconeogenesis from the lactate produced during exercise. The same mechanism accounts for the hypermetabolism of septic shock and cancer cachexia.Harper's ch.17, p.172
It results from the increased oxidation of metabolic fuels needed to provide the ATP and GTP for hepatic gluconeogenesis from the lactate produced during exercise. The same mechanism accounts for the hypermetabolism of septic shock and cancer cachexia.Harper's ch.17, p.172
5 The 2,3-bisphosphoglycerate pathway — 2′+
A bypass, in the erythrocytes of many mammals, of the reaction catalysed by phosphoglycerate kinase, by a process that effectively dissipates as heat the free energy associated with the high-energy phosphate of 1,3-bisphosphoglycerate — so no ATP is formed at that step.
Its purpose is the production of 2,3-bisphosphoglycerate, which binds in the central cavity of haemoglobin, stabilises the T state and lowers oxygen affinity, improving delivery to the tissues.Harper's ch.17, p.172 · Harper's ch.6, p.57
Its purpose is the production of 2,3-bisphosphoglycerate, which binds in the central cavity of haemoglobin, stabilises the T state and lowers oxygen affinity, improving delivery to the tissues.Harper's ch.17, p.172 · Harper's ch.6, p.57
1
Outline briefly the reactions of glycolysis and its regulation.
5′ — 'outline briefly'
Definition and location
Glycolysis is the major pathway for glucose metabolism, occurring in the cytosol of all cells, and is unique in functioning either aerobically or anaerobically. All its enzymes are cytosolic. The overall anaerobic equation is glucose + 2 ADP + 2 Pi → 2 lactate + 2 ATP + 2 H₂O.
The investment phase (steps 1–5)
| Step | Enzyme | Note |
|---|---|---|
| Glucose → glucose 6-phosphate | Hexokinase (muscle) / glucokinase (liver) | Uses ATP; irreversible |
| → Fructose 6-phosphate | Phosphohexose isomerase | |
| → Fructose 1,6-bisphosphate | Phosphofructokinase-1 | Uses ATP; irreversible; the major site of regulation |
| → Two triose phosphates | Aldolase | Glyceraldehyde 3-phosphate + dihydroxyacetone phosphate |
| Interconversion of the trioses | Phosphotriose isomerase | So both halves continue |
The payoff phase (steps 6–10) — occurring twice per glucose
| Step | Enzyme | Yield |
|---|---|---|
| Glyceraldehyde 3-P → 1,3-bisphosphoglycerate | Glyceraldehyde 3-phosphate dehydrogenase | NADH — the only oxidation |
| → 3-Phosphoglycerate | Phosphoglycerate kinase | ATP (substrate level) |
| → 2-Phosphoglycerate | Phosphoglycerate mutase | |
| → Phosphoenolpyruvate | Enolase | Inhibited by fluoride |
| → Pyruvate | Pyruvate kinase | ATP; irreversible |
Net yield: 4 ATP produced − 2 invested = 2 ATP per glucose, plus 2 NADH.
The fate of pyruvate
Anaerobically, NADH cannot be reoxidised through the respiratory chain, so pyruvate is reduced to lactate by lactate dehydrogenase. The purpose is to regenerate NAD⁺ for the glyceraldehyde-3-phosphate dehydrogenase reaction, permitting glycolysis to continue. Aerobically, pyruvate enters mitochondria, is oxidatively decarboxylated to acetyl-CoA, and is oxidised in the citric acid cycle; the NADH enters via the malate-aspartate or glycerophosphate shuttle.
Regulation
Although most reactions are freely reversible, three are markedly exergonic and physiologically irreversible — those of hexokinase (glucokinase), phosphofructokinase and pyruvate kinase — and these are the major sites of regulation. Phosphofructokinase is significantly inhibited at normal intracellular ATP concentrations, an inhibition rapidly relieved by 5′AMP formed as ADP accumulates. Cells capable of gluconeogenesis possess different enzymes to reverse these three steps: glucose 6-phosphatase, fructose 1,6-bisphosphatase, and pyruvate carboxylase with PEP carboxykinase.
Marking guide: definition, location and overall equation 1 · the ten steps with at least six enzymes named 1.5 · the two ATP-generating steps identified 0.5 · net yield of 2 ATP 0.5 · the fate of pyruvate under both conditions, with the reason for lactate 1 · the three irreversible regulatory enzymes 0.5.
2
Elucidate the structure, function and regulation of the pyruvate dehydrogenase complex.
8′ — 'elucidate'
Function
The pyruvate dehydrogenase complex catalyses the oxidative decarboxylation of pyruvate to acetyl-CoA, and constitutes the irreversible route from glycolysis to the citric acid cycle. Its irreversibility has a profound consequence: once carbon has entered acetyl-CoA it cannot return to pyruvate, which is why fatty acids cannot be converted to glucose.
Structure
Three catalytic enzymes: pyruvate dehydrogenase (PDH), dihydrolipoamide transacetylase and dihydrolipoamide dehydrogenase.
Five cofactors: thiamin pyrophosphate (TPP), lipoic acid, NAD⁺, FAD and CoASH. Note that four derive from B vitamins — thiamin, riboflavin, niacin and pantothenic acid — so the complex is exquisitely sensitive to vitamin deficiency.
Regulation — two mechanisms
1 · End-product inhibition. The enzyme is inhibited by its own products, acetyl-CoA and NADH.
2 · Covalent modification. Phosphorylation of three serine residues on the pyruvate dehydrogenase component, by a kinase, decreases activity; dephosphorylation by a phosphatase increases it. The dephosphorylated form (PDH-a) is the active one.
The kinase is activated by increases in the [ATP]/[ADP], [acetyl-CoA]/[CoA] and [NADH]/[NAD⁺] ratios — every one of which signals an abundant energy supply.
Physiological consequences
PDH, and therefore glycolysis, is inhibited not only by a high energy potential but also when fatty acids are being oxidised. In starvation, free fatty acid concentrations rise, decreasing the proportion of enzyme in the active form and leading to a sparing of carbohydrate — preserving glucose for the brain, which cannot use fatty acids. Conversely, in adipose tissue, where glucose provides acetyl-CoA for lipogenesis, the enzyme is activated in response to insulin.
Clinical aspects — inhibition leads to lactic acidosis
- Arsenite and mercuric ions react with the –SH groups of lipoic acid, allowing pyruvate to accumulate.
- Dietary thiamin deficiency deprives the complex of TPP. Many alcoholics are thiamin deficient — from poor diet and because alcohol inhibits thiamin absorption — and may develop potentially fatal pyruvic and lactic acidosis.
- Inherited PDH deficiency, from defects in one or more components, presents with lactic acidosis, particularly after a glucose load.
Because of the dependence of the brain on glucose as a fuel, these defects commonly cause neurological disturbances.
Marking guide: function as the irreversible link to the citric acid cycle 1 · three enzymes named 1.5 · five cofactors named 1.5 · end-product inhibition 1 · covalent modification with the three serines and the direction of each 1.5 · the starvation/carbohydrate-sparing consequence 1 · one clinical cause of lactic acidosis 0.5.