Lecture 10. The Citric Acid Cycle Flashcards
Why is pyruvate oxidised?
Further oxidation of pyruvate in citric acid cycle releases most of the energy out of the pyruvate molecule
What was the interpretation of the sparker effect?
Organic acids act as a catalyst and increases the O₂ consumption
How much pyruvate oxidation can be sparked by one molecule of oxaloacetate?
Infinite
What is malonate?
A potent inhibitor of respiration in all animal tissues
What type of inhibitor is malonate?
Competitive inhibitor - mimics succinate
What does the citric acid cycle break down?
Carbohydrates, fats and amino acids
Where does the citric acid cycle take place?
The mitochondrial matrix
What is pyruvate from glycolysis converted to before being entered into the citric acid cycle?
Acetyl CoA
What is used to convert pyruvate into acetyl CoA?
Coenzyme A - (catalysed by pyruvate dehydrogenase multi-enzyme complex)
What makes up the pyruvate dehydrogenase complex?
Pyruvate dehydrogenase component (E1)
Dihydrolipoyl transacetylase (E2)
Dihydrolipoyl dehydrogenase (E3)
Coenzyme A function
Serves as a carrier of activated acyl groups linked via a thioester bond
What is coenzyme A a derivative of?
An adenine nucleotide
What is flavin adenine dinucleotide (FAD)?
A coenzyme for redox reactions - it accepts two electrons and two protons
What forms the swinging arm of E2?
Lipoamide formed by amide linkage of lipoic acid to a lysine residue of the enzyme
Function of E1
Decarboxylates pyruvate
Lipoamide picks up acetyl group
Function of E2
Transfers to CoA
Function of E3
Regenerates lipoamide
Structure of E1E2 complex
E2 forms the core
E1 is the outer layer
What is the definition of a multi-enzyme complex?
Groups of two or more non-covalently associated enzymes catalyse two or more sequential steps in a metabolic pathway
Advantages of multi-enzyme complexes
Product of the first reaction in the sequence remains attached
Serves directly as a substrate for the second reaction Therefore rate of second reaction not limited by diffusion
Can channel intermediates between successive enzymes, thereby minimising side reactions
The reactions may be coordinately regulated
How many times does the citric acid cycle go round per glucose molecule
Twice
When are NADH and FADH₂ re-oxidised?
During oxidative phosphorylation
How is pyruvate DH switched off?
Phosphorylation - Kinase is stimulated by acetyl CoA, ATP and NADH
How is pyruvate DH switched on?
Dephosphorylation - Kinase is inhibited by ADP and NAD⁺
What are the principal negative regulators in the citric acid cycle?
ATP and NADH
What is the main positive regulator in the citric acid cycle?
The need for energy and for carbon skeletons
What will happen to the citric acid cycle is oxaloacetate is depleted?
The cycle will stop
What are anaplerotic reactions?
Reactions that replenish cycle intermediates to prevent withdrawl
What is the main anaplerotic reaction in humans?
Pyruvate + CO₂+ ATP + H₂O → oxaloacetate + ADP + Pi + 2H⁺
What catalyses the main anaplerotic reaction in humans?
Pyruvate carboxylase
What amino acids can be used in anaplerotic reactions if needed?
Glucogenic amino acids
What amino acids can’t be used in anaplerotic reactions?
Ketogenic amino acids
