Medium-chain acyl-CoA dehydrogenase (MCAD) is an enzyme involved in β-oxidation, and is encoded by the autosomal ACADM gene. MCAD deficiency is caused by a mutation in ACADM, and results in impaired ability to digest medium-chain fatty acids for energy, and in their subsequent accumulation. Which of the following interventions would best relieve the negative effects of MCAD deficiency?

Question

Medium-chain acyl-CoA dehydrogenase (MCAD) is an enzyme involved in β-oxidation, and is encoded by the autosomal ACADM gene.  MCAD deficiency is caused by a mutation in ACADM, and results in impaired ability to digest medium-chain fatty acids for energy, and in their subsequent accumulation.  Which of the following interventions would best relieve the negative effects of MCAD deficiency?

Quizplus · Accepted Answer

11ecba2d_0e42_dbad_a3bf_e3f2b2caf870_MD0008_00 Inborn errors of metabolism are genetic disorders caused by deleterious mutations in genes that code for metabolic enzymes. These disorders result in the accumulation of metabolites upstream of the affected enzyme and decreased levels of the downstream products in the pathway. The resulting changes in metabolite levels frequently have negative clinical effects such as lethargy, impaired development, and toxicity. According to the question, medium-chain acyl-CoA dehydrogenase (MCAD) is an enzyme involved in β-oxidation, a metabolic process that hydrolyzes fatty acids into acetyl-CoA and generates reduced electron carriers for ATP production. β-oxidation is an important source of ATP during periods of fasting, after glycogen stores are exhausted. Because mutations within the gene that encodes MCAD result in impaired β-oxidation, therapies for MCAD deficiency should be aimed at restoring energy production either by supplementing the deficient enzyme with a functional version or providing an alternate fuel source that follows a different metabolic pathway. A diet rich in glucose is an effective therapy because, like β-oxidation, digestion of glucose leads to the production of acetyl-CoA, reduced electron carriers, and ultimately ATP. (Choice A) Although β-oxidation occurs in the mitochondria, the gene that encodes MCAD (ACADM) is autosomal. Autosomal genes are found in the nucleus, so mitochondrial gene therapy would neither affect functional MCAD levels nor relieve the negative effects of MCAD deficiency. (Choice B) Long-chain fatty acids are digested into medium-chain fatty acids, which must be processed by MCAD. Supplementation with long-chain fatty acids in an MCAD-deficient patient would lead to an increased buildup of medium-chain fatty acids and yield little ATP. (Choice C) β-oxidation is an important energy source during periods of fasting. MCAD deficiency inhibits β-oxidation, so fasting is harmful to MCAD-deficient individuals. Educational objective: Inborn errors of metabolism are genetic disorders that result in impaired metabolic pathways. These disorders are typically treated either by supplementing the deficient enzyme with a functional version or by providing an alternate source of the desired metabolic products. Alternate sources must follow a separate, independent metabolic pathway from the defective one.

Medium-Chain Acyl-CoA Dehydrogenase (MCAD) Is an Enzyme Involved in β-Oxidation