The citrate-malate shuttle allows the cell to produce fatty acid with excess acetyl-CoA for storage. The principle is similar to that of insulin, which turns excess glucose in the body into glycogen for storage in the liver cells and skeletal muscles, so that when there is a lack of energy intake, the body could still provide itself with glucose by breaking down glycogen. The citrate-malate shuttle enables more compact storage of chemical energy in the body in the form of fatty acid by transporting acetyl-CoA into the cytosol for fatty acid and cholesterol synthesis. The lipids produced can then be stored so that they can be used in the future.
Acetyl-CoA is generated in the mitochondrial matrix from two sources: pyruvate decarboxylation in glycolysis and the breakdown of fatty acids through β-oxidation, which are both essential pathways of energy production in humans. Pyruvate decarboxylation is the step that connects glycolysis and the Krebs cycle and is regulated by the pyruvate dehydrogenase complex when blood glucose levels are high. Otherwise, fatty acid β-oxidation occurs, and acetyl-CoA is required to generate ATP through the Krebs cycle. In a subject with defective citrate-malate shuttle, acetyl-CoA in mitochondria cannot exit into the cytosol. Fatty acid synthesis is hence hindered, and the body would not be able to store excess energy as efficiently as a normal subject.
In addition, improper functioning of the citrate-malate shuttle can result in disruption of the Krebs cycle.