L15 - The TCA Cycle

Question 1

Conversion of Pyruvate to Acetyl CoA (link reaction)

Answer 1

Ch₃COCOOH + CoASH → Ch₃COSCoA + CO₂

PYRUVATE DEHYDROGENASE

(NAD+ converted to NADH + H+)

Irreversible reaction

Occurs in mitochondria

Oxidative decarboxylation (remove CO₂ and Oxidise Pyruvate and reduce NAD)

Question 2

Regulation of Pyruvate dehydrogenase:

Answer 2

1. Allosteric regulation

CoA-SH and NAD⁺ activate enzyme (reactants)

Acetyl CoA and NADH inhibit enzyme so slow reaction down (products)

2. Covalent modification

Phosphorylation inhibits enzyme (kinase) Dephosphorylation activates enzyme (phosphatase)

Question 3

TCA Cycle (reaction, location, tissues, and functions):

Answer 3

Reaction: Oxidation of Acetyl CoA to CO₂ and water

Location: Inside mitochondria (mitochondrial matrix)

Tissues: All tissues with mitochondria (not RBC or white muscle fibres)

Functions:

Energy trapping

Biosynthesis of intermediates - take out reagents and use it to make other molecules

Question 4

TCA Cycle: THE PATHWAY

Answer 4

Oxaloacetate + Acetyl CoA→ citrate

CITRATE SYNTHASE (Condensation reaction)

Citrate ⇔ Isocitrate

ACONITASE (Isomerisation)

Isocitrate → a-ketoglutarate

ISOCITRATE DEHYDROGENASE

Add NAD⁺ to give NADH and H⁺

Release CO₂

a-ketoglutarate → succinyl-CoA

a-KETOGLUTARATE DEHYDROGENASE

Add NAD⁺ to give NADH and H⁺

Add CoA-SH and release CO₂

Succinyl-CoA ⇔ Succinate

SUCCINYL-CoA SYNTHETASE

ADP + Pi = ATP (GTP in liver)

Make triphosphate with high phosphoryl transfer (high energy phosphate).

Release CoA

Succinate ⇔ Fumarate

SUCCINATE DEHYDROGENASE

FAD goes to FADH₂

Fumarate ⇔ Malate

FUMARASE

Add H₂O

Malate ⇔ Oxaloacetate

MALATE DEHYDROGENASE

NAD⁺ becomes NADH and H⁺

Question 5

Metabolic importance of Oxaloacetate and how it’s produced from Pyruvate:

Answer 5

1. Oxaloacetate to aspartate via transamination reaction. Aspartate → other amino acids, purines and pyrimidines.

Provides source of molecules that can be taken out for use in metabolism. Usually reversible so can be taken back into pathway.

2. Oxaloacetate to phosphoenolpyruvate

PEP CARBOXYKINASE

Phosphoenolpyruvate then converted to Pyruvate or Glucose

Oxaloacetate can be made from Pyruvate:

Pyruvate →Oxaloacetate

PYRUVATE CARBOXYLASE

ATP becomes ADP and Pi. CO₂ also added.

Question 6

TCA cycle - source of biosynthesis precursors (6 steps):

Answer 6

1. Malate ⇔ Pyruvate MALIC ENZYME
2. Citrate ⇔ fatty acids and sterols.
3. α-Ketoglutarate ⇔ Glutamate via transamination. Glutamate → other A.A and purines
4. Oxaloacetate ⇔ Aspartate.

Aspartate → other A.A, purines and pyrimidines.

5. Oxaloacetate ⇔ phosphoenolpyruvate Phosphoenolpyruvate→Glucose/Pyruvate
6. Pyruvate ⇔ Oxaloacetate