The tricarboxylic acid cycle

What is cellular respiration?

• Catabolic process in which cells consume
  O2 and produce CO, to break down organic molecules

• Carbohydrates, lipids, and amino acids are catabolised in three stages of cellular respiration

• Provides more energy (ATP) from glucose than glycolysis

What is stage 1 of the citric acid cycle?

Acetyl-CoA production

• organic fuels such as glucose are oxidised to two-carbon fragments in the form of acetyl-CoA

• Site of synthesis: mitochondrial matrix

• Generates ATP/NADH

What is stage 2 of the citric acid cycle?

Acetyl-CoA oxidation

• Also known as the tricarboxylic acid Cycle/Krebs cycle

• central hub of cellular metabolism

• meets cellular energy requirements by oxidising the products of carbohydrate and fat metabolism

• Generates NADH, FADH2 and GTP

What is step 3 of the citric acid cycle?

Oxidative decarboxylation by isocitrate dehydrogenase

• NAD-dependent enzyme occurs in the mitochondrial matrix and serves in the citric acid cycle

• NADP-dependent enzymes are present in both the mitochondrial matrix and the cytosol, generating NADPH necessary for fatty acid and sterol synthesis.

What is step 4 of citric acid cycle?

Oxidative decarboxylation by a-Ketoglutarate dehydrogenase

• Catalyses the conversion of a-ketoglutarate to succinyl-CoA

• Produces NADH directly, providing electrons for the respiratory chain

• Highly regulated enzyme- determines the metabolic flux through the TCA cycle

What is step 5 citric acid cycle?

• Reversible conversion of succinyl-CoA to succinate, coupled with the phosphorylation of GDP to GTP

• GTP formed by succinyl-CoA synthetase donates its terminal phosphoryl group to ADP to form ATP, in a reversible reaction catalysed by nucleoside diphosphate kinase

What is step 6 of the citric acid cycle?

Oxidation of an alkane to alkene by succinate dehydrogenase

• SDH is embedded in the inner membrane of the mitochondria, allowing FADH2 to directly transfer its electrons into the electron transport chain

• Electron flow through these carriers to the final electron acceptor, 02, is coupled to the synthesis of ~1.5 ATP molecules

What is Step 7 of the citric acid cycle?

Hydration of a double bond by fumarase

• reversible hydration/dehydration of fumarate to malate

What is step 8 of the citric acid cycle?

Oxidation of malate to oxaloacetate by malate dehydrogenase

• regenerates oxaloacetate for the next cycle

How is the citric acid cycle regulated?

• regulated at highly thermodynamically favourable steps

• general regulatory mechanisms

  • activated by substrate availability

  • inhibited but product accumulation

• both glycolysis and TCA cycle pathways are inhibited by high levels of ATP, NADH and citrate