MCAD

1400 Words3 Pages

Triglycerides are a main source of energy for humans, which are storage molecules composed of fatty acids that may undergo fatty acid beta-oxidation when in need of energy (D. R. de Assis et al, 2003). Medium-chain acyl-CoA dehydrogenase deficiency (MCAD deficiency) is the most commonly diagnosed mitochondrial fatty acid β-oxidation disorder that prevents fatty acid conversion to energy (Rinaldo et al., 2002). MCAD deficiency is caused by mutations in the gene coding for the MCAD enzyme, and the disorder occurs in 1 of every 17,000 people, with the highest frequency in Northern European populations (Kompare & Rizzo, 2008; Rinaldo et al., 2002). Individuals are often diagnosed using genetic and molecular testing by looking at DNA, as well as the contents of urine samples (Matern & Rinaldo, 2012 ). Newborn screening may help identify affected individuals before the onset of symptoms and take preventative measures against this disorder (Kompare & Rizzo, 2008). MCAD normally metabolizes medium-chain acyl-CoAs in the matrix of the mitochondria. In fatty acid β-oxidation, MCAD catalyzes the dehydrogenation of acyl-CoAs with four to 12 carbons in chain length (Matern & Rinaldo, 2012). In MCAD deficiency, this initial dehydrogenation step of the beta-oxidation process if significantly hindered, resulting in ineffective fatty acid degradation. A deficiency in the MCAD enzyme is caused by premature degradation due to an accumulation of improperly folded proteins and tetramer assembly. Beta-oxidation is severely impacted because the enzyme also has reduced enzymatic function due to higher Km values for medium-chain fatty acid substrates and lower affinity for its substrates (Kieweg et al., 1997). Because access of energy via beta-oxidation... ... middle of paper ... ... which is catalyzed by b-ketoacyl CoA thiolase. The products are acetyl-CoA and a long chain fatty acyl CoA that is 2 carbons shorter than the original fatty acyl CoA. One complete round of β-oxidation cleaves 2 carbons from the fatty acid chain, and the process continues until the entire fatty acid chain is broken down into acetyl propinoyl CoA. For example, an 18 carbon chain fatty acid would need to go through 9 rounds of β-oxidation in order to be completely metabolized. Thus, a normal ACADM gene will encode for a fully functioning medium-chain specific acyl-Coenzyme A dehydrogenase. In fatty acid β-oxidation, the MCAD enzyme is responsible for catalyzing the initial step of the mitochondrial β-oxidation pathway for medium-chain fatty acids (C6-C12). The initial step is crucial to allow the progresssion of the β-oxidation pathway. MCAD Deficiency and β-oxidation

Open Document