The Link Reaction And TCA Cycle

Question 1

What is acetyl-coA

Answer 1

1. Entry substrate for the citric acid cycle. It combines with oxaloacetate to form citrate
2. The building block for fatty acid synthesis (lipogenesis)
3. Contributes carbon atoms for cholesterol synthesis
4. Substrate for amino acids such as acetylcholine
5. Co-substrate for histone acetyltransferase enzymes that acetylate histones

Question 2

What are the other sources of acetyl coA

Answer 2

1. Catabolism of fatty acids by hydrolysis produces a-coA
2. Fatty acid oxidation occurs in mitochondria and peroxisomes, with acetyl coA the end product of the oxidation
3. Protein can be broken down into amino acids which can be converted to acetyl coA

Question 3

Give a summary of the TCA/Krebs/Citric acid cycle

Answer 3

Citrate—>Isocitrate (isomerism)—>a-ketoglutarate (oxidative decarboxylation)—>Succinyl CoA (oxidative decarboxylation)—>Succinate (Phosphorylation)—>fumarate(reduction)—>malate(hydration)—>oxaloacetate(reduction)—>Citrate(hyrdration+CoA)

Main reactions in TCA cycle:
1. Oxaloacetate + Acetyl CoA —> citrate + CoA
2. Citrate isomerised by aconitase
3. Isocitrate oxidised and decarboxylated to a-KG
4. Oxidative decarboxylation and addition of CoA of a-KG results in Succinyl-CoA (aKG+NAD++COA—>Succinyl CoA+CO2+NADH

Reactions continued:
1. SuccinylcoA + GDP + Pi —> Succinate + CoA +GTP (substrate level phosphorylation)
2. Succinate + FAD —> Fumarate + FADH2 (succinate dehydrogenase)
3. Fumarate + H20 —> Malate (fumarase hydration)
4. Malate + NAD —> Oxaloacetate + NADH + H+ (malate dehydrogenase)

Question 4

Summary of TCA cycle reactions

Answer 4

1. Two decarboxylations
2. Four reductions
3. One GTP generated in substrate level phosphorylation
4. Two water molecules are consumed

Overall reaction
Acetyl-CoA +3 NAD+ +FAD +GDP +P +2H2O —> CoA-SH +3NADH + FADH2 +3H+ +GTP +2CO2

Question 5

How is the TCA cycle regulated

Answer 5

1. Pyruvate —> Acetyl coA
   Positive regulator: AdP and pyruvate
   Negative regulator: ATP, acetyl coA and NADH
2. Isocitrate to a ketoglutarate
   Positive regulator: ADP
   Negative regulator: ATP and NADH
3. A ketoglutarate to succinyl coA
   Negative regulator: ATP, NADH, succinyl coA
4. In muscle Ca2+ is a positive regulator on reactions in the TCA cycle

Question 6

Describe how the TCA cycle is a source of precursor molecules for different bio synthetic pathways

Answer 6

1. Fatty acid and sterol synthesis pathway (citrate)
2. Glutamate, amino acids and purines pathway (a-ketoglutarate)
3. Porphyrins, heme, chlorophyll pathway (succinyl coA)
4. Glucose pathway. Aspartate, amino acids, purines, pyrimidines pathway (oxaloacetate)

Question 7

Define and give examples of anaplerotic pathways for the TCA cycle

Answer 7

1. Anaplerotic pathways replenish intermediates within the TCA cycle
2. Major anaplerotic reaction is the ATP-dependent carboxylation of pyruvate to oxaloacetate
3. Phosphoenolpyruvate (PEP) can be carboxylated to oxaloacetate
4. A malic enzyme can interconvert pyruvate and malate
5. Glutamic acid -> aKG and aspartic acid -> Oxaloactetate by transaminases