Malonyl-CoA is a fatty acid precursor that is very important in the body’s regulation of fatty acid metabolism. It is necessary for the function of an enzyme known as Malonyl-CoA decarboxylase. A genetic deficiency for this enzyme can result in a very rare disorder known as Malonyl-CoA decarboxylase deficiency.
The human body obtains fatty acids both from dietary sources and from fatty acid biosynthesis. These compounds are necessary to be broken down as sources of energy, as components of cellular structures such as membranes, and as hormones. Excessive amounts of carbohydrates and protein in one’s diet can be easily converted to fatty acids. When needed for energy, the fatty acids are then readily broken down.
The metabolism of fatty acids involves cofactors — non-protein components that loosely bind to an enzyme, making it a coenzyme. CoA is the coenzyme utilized in the synthesis of fatty acids. The essential control point in the biosynthesis of fatty acids is the production of Malonyl-CoA. This coenzyme is produced from the addition of carbon dioxide to Acetyl-CoA. The role of Malonyl-CoA in fatty acid biosynthesis is to provide growing fatty acid chains with two units of carbon.
When fatty acids are needed for energy, the reverse reaction takes place under some conditions. Acetyl-CoA can be used in energy production. Malonyl-CoA decarboxylase catalyzes the breakdown of Malonyl-CoA, into Acetyl-CoA and carbon dioxide. Mutations in the gene for this enzyme cause Malonyl-CoA decarboxylase deficiency. This disrupts fatty acid metabolism in the body.
With this condition, fatty acids can no longer be converted to energy. This can lead to low blood sugar, also known as hypoglycemia. A lack of energy from fatty acids poses a particular problem for heart muscle, which relies heavily on these compounds as a source of energy. There is also a build-up of fatty acid breakdown products, which contributes to other symptoms.
This disorder manifests in early childhood, almost always with delayed development. Additional symptoms include seizures, vomiting, diarrhea, and weak muscle tone. A common infirmity is weakening and enlargement of the heart muscle. Experts suggest that a high-fat, low-carbohydrate diet might mitigate some of the symptoms of this disorder.
To inherit this enzyme deficiency, a person must inherit a copy of a defective gene from each parent. A carrier with only one copy of a defective gene will usually not show any symptoms. It requires two copies of defective genes to inherit a decarboxylase deficiency. Fortunately, this is an extremely rare disorder. As of 2010, fewer than 30 cases have been reported.