Question 22

Outline the importance of the citric acid cycle in metabolism

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College Answer

Only an outline of the importance of the citric acid cycle (CAC) was expected, and not a 
detailed understanding. Candidates struggled to appreciate its importance. For a good 
answer candidates were expected to mention that the CAC has two main functions: energy 
production and biosynthesis. Some understanding of the overall reaction 
( AcCoA + 3NAD+ + FAD + GDP + Pi + 2H2O  2CO2 + 3NADH + FADH2 + GTP + 
CoA ), the link between oxidation of metabolic fuel (carbohydrates, lipids and protein) and 
aerobic energy production (oxidative phosphorylation), that Acetyl CoA is final common 
product of these oxidations (Glucose via glycolysis (cytoplasm), Free fatty acids via β 
oxidation (mitochondrial matrix) and Amino acids – glucogenic and ketogenic reactions), 
that CAC is first stage of aerobic respiration, requires oxygen to proceed, that the CAC 
together with oxidative phosphorylation accounts for 2/3 to 3/4 of ATP generated from fuel 
oxidation and anabolic involvement, whereby several biosynthetic pathways utilize CAC 
intermediates, e.g. Glucose biosynthesis (gluconeogenesis) via malate then oxaloacetate, fatty acid and cholesterol biosynthesis via citrate + CoA  AcCoA, Amino acid biosynthesis 
via reductive amination and transamination reactions, Porphyrin (organic component of 
haeme) via succinyl CoA and Purine and pyrimidine biosynthesis – precursors of nucleotide 
bases for DNA and RNA