MTC Pathway Questions MD1010

What are the three irreversible steps of glycolysis and why are they important? [3 marks]

glucose → glucose-6-phosphate by hexo/glucokinase

fructose-6-phosphate → fructose-1,6-bisphosphate by PFK-1

phosphoenol pyruvate → pyruvate by pyruvate kinase

These reactions have large - ΔG values and regulate glycolytic direction.

Describe the role of (PFK-1) in glycolysis and how it is regulated. [3 Marks]

PFK-1 catalyses the conversion of fructose-6-phosphate to fructose-1,6-bisphosphate, activated by AMP and F26BP, inhibited by ATP and citrate.

How many ATP molecules are generated from anaerobic glycolysis of one glucose molecule? Show your work. [2 Marks]

1 ATP used to convert glucose to glucose-6-phosphate

1 ATP used to convert fructose-6-phosphate to fructose-1,6-bisphosphate

2 ATP gained in the conversion of 1,3-bisphosphoglycerate to 3-phosphoglycerate

2 ATP gained in the conversion of phosphoenol pyruvate to pyruvate

State the major substrates used in gluconeogenesis that don't come directly from TCA or Glycolysis [1.5 Marks]

lactate, glycerol, glucogenic amino acids such as alanine

Why can fatty acids not be used to produce net glucose in humans? [2 marks]

fatty acids produce acetyl-coa during beta-oxidation, which cannot be converted back into pyruvate in humans, meaning that any carbon atoms entering the tca cycle as acetyl-coa are lost as co2

Describe the bypass reactions used to overcome irreversible glycolytic steps during gluconeogenesis. [3 marks]

Pyruvate is converted to oxaloacetate by pyruvate carboxylase and then to phosphoenolpyruvate by PEP carboxykinase. F16BPtase bypasses PFK-1 and G6Ptase bypasses hexokinase.

Describe the major steps of hepatic fructose metabolism. [4 marks]

fructose → fructose-1-phosphate by fructokinase

fructose-1-phosphate → dihydroxyacetone and glyceraldehyde phosphate by aldolase b

DHAC and glyceraldehyde → glycolytic intermediates and enter glycolysis downstream of PFK-1

Explain why high fructose intake promotes lipogenesis. [3 Marks]

fructose bypasses the regulatory pfk-1 step of glycolysis, causing an unregulated production of triose phosphates and acetyl-coa, which is converted to fatty acids and triglycerides

What enzyme deficiency causes hereditary fructose intolerance and what metabolite accumulates? [1 Mark]

aldolase B deficiency, resulting in accumulation of fructose-1-phosphate.

What is the first committed step of glycogenesis? [0.5 Marks]

Formation of UDP-Glucose

Describe the role of glycogen synthase in glycogenesis and how insulin affects it. [2 Marks]

catalyses formation of alpha-1,4-glycosidic bonds, insulin activates it by promoting its dephosphorylation

Why is glycogen highly branched? [1 Mark]

increases glycogen solubility and allows rapid glucose release with multiple terminal ends for enzymatic activity

Describe the hormonal regulation of glycogenolysis. [3 marks]

Glucagon and adrenaline stimulate glycogenolysis through activation of the cAMP pathway, which activates glycogen phosphorylase. Insulin inhibits glycogenolysis.

What is the role of glycogen phosphorylase? [1 Mark]

cleaves alpha-1,4-glycosidic bonds to release glucose-1-phosphate form glycogen

Why can the liver release free glucose into blood but skeletal muscle cannot? [1.5 Marks]

liver contains glucose-6-phosphatase to convert G6P into free glucose, where skeletal muscle does not

Describe the regulation of hormone-sensitive lipase. [ 2 Marks]

activated by glucagon and adrenaline via cAMP-dependent phosphorylation and inhibited by insulin.

State the products of triglyceride breakdown. [1 Mark]

Glycogen, three fatty acids

Explain why uncontrolled diabetes increases ketone body production. [4 Marks]

Low insulin levels increase lipolysis and fatty acid delivery to the liver. Increased β-oxidation generates excess acetyl-CoA, which is converted into ketone bodies because oxaloacetate is diverted to gluconeogenesis.

Describe the four recurring steps of β-oxidation. [3.5 Marks]

oxidation, hydration, oxidation, cleavage -> each cycle produces acetyl-coa, nadh, fadh2

What is the role of carnitine in fatty acid oxidation? [1 mark]

Transports long-chain fatty acids into the mitochondrial matrix for β-oxidation.

Calculate the ATP yield from one round of β-oxidation. [1.5 Marks]

1 NADH and 1 FADH₂, generating approximately 4 ATP in total.

Name the rate-limiting enzyme of the TCA cycle and describe its regulation. [2 Marks]

Isocitrate dehydrogenase is the rate-limiting enzyme of the TCA cycle. It is activated by ADP and inhibited by ATP and NADH.

How many NADH, FADH₂ and GTP are produced per acetyl-CoA in the Krebs cycle? [1.5 Marks]

3 NADH, 1 FADH₂ and 1 GTP

Why is the TCA cycle considered amphibolic? [1 Mark]

functions in both catabolic energy production and anabolic biosynthesis

Name the four complexes of the ETC and state their primary role. [4 Marks]

Complex I (NADH-Q Reductase) transfers electrons from NADH to coenzyme Q, Complex II (Succinate DH) transfers electrons from FADH₂ to coenzyme Q, Complex III (Cyotchrome c reductase) transfers electrons from coenzyme Q to cytochrome c, and Complex IV (cytochrone C Oxidase) transfers electrons to oxygen to form water.

Describe four ETC inhibitors and their mechanism of action. [4 Marks]

Rotenone - inhibits Complex I by blocking electron transfer to coenzyme Q

Antimycin A - inhibits Complex III.

Cyanide and carbon monoxide - inhibit Complex IV by preventing reduction of oxygen

Explain how cyanide poisoning causes death at a cellular level. [3 Marks]

Cyanide inhibits Complex IV of the ETC by binding cytochrome oxidase, preventing oxygen reduction and oxidative phosphorylation. ATP production ceases, causing cellular hypoxia and death.

Name the two mobile electron carriers of the ETC and describe where they transfer electrons. [2.5 Marks]

Coenzyme Q carries electrons from Complexes I and II to Complex III, while cytochrome c transfers electrons from Complex III to Complex IV.

Describe the chemiosmotic theory of ATP synthesis. [3 Marks]

etc pumps protons into the intermembrane space, creating an electrochemical gradient. this causes protons to flow back through atp synthase and drive atp production

Explain the difference between ETC inhibitors and uncouplers. [3 Marks]

ETC inhibitors block electron transport and stop ATP production

Uncouplers dissipate the proton gradient so electron transport continues but ATP synthesis decreases and heat is produced.

What is the first committed step of fatty acid synthesis? [1 Mark]

conversion of acetyl-CoA to malonyl-CoA by acetyl-CoA carboxylase.

Describe the role and regulation of acetyl-CoA carboxylase. [2.5 Marks]

Acetyl-CoA carboxylase catalyses formation of malonyl-CoA and is the rate-limiting enzyme of fatty acid synthesis. It is activated by citrate and inhibited by glucagon and palmitoyl-CoA.

Describe the two major functions of the pentose phosphate pathway. [2 Marks]

The pentose phosphate pathway produces NADPH for reductive biosynthesis and antioxidant defence and produces ribose-5-phosphate for nucleotide synthesis.

What is the rate-limiting enzyme of the PPP and how is it regulated? [1.5 Marks]

Glucose-6-phosphate dehydrogenase, activated by NADP⁺ and inhibited by NADPH.

Why are red blood cells particularly dependent on the PPP? [1 Mark]

No mitochondria, NAPH protects from oxidative stress

Describe the major steps of the urea cycle.

ATP +HCO3 + NH4 -> carbamoyl phosphate by cpt1

cp + ornithine -> citrulline by ornithine transcarbamoylase

citrulline + aspartate -> arginosuccinate by arginosuccinate synthase

arginosuccinate -> arginine by arginosuccinate lyase, where fumarate is removed

arginine -> ornithine by arginase, where urea is removed

Name two amino acids involved in the urea cycle and describe their role. [2 Marks]

Ornithine accepts carbamoyl phosphate to form citrulline, while aspartate donates a nitrogen atom during argininosuccinate formation.

What is the rate-limiting enzyme of the urea cycle and how is it regulated? [1 Mark]

carbamoyl phosphate synthetase, activated by n-acetylglutamate

Describe the link between the TCA cycle and the urea cycle. [2 Marks]

fumarate produced into the urea cycle enters the tca cycle while oxaloacetate from the tca cycle can be converted into aspartate for the urea cycle

Why does liver failure cause elevated blood ammonia levels? [1 Mark]

Liver failure impairs the urea cycle, reducing ammonia detoxification and causing hyperammonaemia.

Describe the fate of amino groups during protein metabolism. [2 marks]

Amino groups are transferred by transamination reactions, released as ammonia by oxidative deamination and converted into urea in the liver for renal excretion.

Outline the process of gluconeogenesis from glycerol

glycerol → glycerol-3-phosphate by glycerol kinase, converting ATP to ADP
glycerol-3-phosphate → dihydroxyacetone phosphate by glycerol-3-phosphate dehydrogenase, converting NAD to NADH
dihydroxyacetone phosphate → fructose-1,6-bisphosphate
fructose-1,6-bisphosphate → fructose-6-phosphate by fructose-1,6-bisphosphatase
fructose-6-phosphate → glucose-6-phosphate by phosphohexose isomerase
glucose-6-phosphate → glucose by glucose-6-phosphatase

What is the cori cycle?

provides a mechanism to convert lactate produced by anaerobic glycolysis in muscle cells to glucose using the gluconeogenesis pathway in liver cells

How is gluconeogenesis regulated?

glucagon stimulates, insulin, ADP, AMP inhibits

What is an antiporter?

transporter that transports one solute in one direction while transporting a second solute in the opposite direction

What is a symporter?

Simultaneously transports a sugar (or amino acid) and an ion (usually Na or H ion) across a membrane.

What is Km and what does it mean?

the affinity constant, equal to the concentration of the substrate that gives a velocity equal to half Vmax
Low = high affinity
High = low affinity

What are the different kinds of inhibition?

competitive, uncompetitive, non-competitive

What is uncompetitive inhibition?

when an inhibitor binds to the enzyme-substrate complex, preventing the release of products

What is non-competitive inhibition?

when an inhibitor binds at a site other than the active site, changing enzyme structure so that normal substrate binding cannot occur

What is competitive inhibition?

when an inhibitor binds to the active site, preventing the substrate from binding

How can the different kinds of inhibition be overcome?

competitive: increasing substrate concentration
non-competitive: cannot be overcome

What is an allosteric enzyme and its function?

n enzyme that regulates its own catalytic activity by binding a molecule (an effector) at a specific site other than its active site

Outline the process of fructose metabolism.

fructose → fructose-1-phosphate by fructokinase, converting ATP to ADP
F1P → glyceraldehyde/dihydroxyacetone phosphate by aldolase B
glyceralde

Outline the process of galactose metabolism.

How many ATP’s can be produced from one NADH, FADH?

Outline the functions and regulation of pyruvate dehydrogenase.

Outline the process of the TCA cycle.

What are reactive oxygen species and how are they derived?

What is glutathione, and why is it important?

Outline the process of ketone body synthesis.

When does ketone body synthesis occur?

What is the process of the urea cycle?

What is the function of DNA polymerase?

How is transcription and translated regulated?

What do anticodons bind to?

Outline the process of PCR?

Outline the process of the malate aspartate shuttle?

Outline the process of the other shuttle look it up

How much ATP is produced during beta-oxidation?

What are the different kinds of mutations?