MCAD medium-chain fatty

Medium-chain fatty acyi CoA dehydrogenase (MCAD) deficiency impairs metaboiism of medium-chain (C6-Ci2) fatty acids. 

Table 3.1.3 Pathologic acylglycine species detected by organic acid analysis. CoA coenzyme A, FAO fatty acid oxidation, ILE isoleucine, LEU Leucine, MCAD medium-chain acyl-CoA dehydrogenase, MET methionine,...

A couple has a child who has been diagnosed with medium-chain acyl coenzyme A (CoA) dehydrogenase deficiency (MCAD), a condition that allects the body s ability to metabolize medium-chain fatty acids. This couple is now expecting another child. What is the risk that this child will have MCAD ... 

Fig. 5. Diacylglycerol (DAG) stimulates mRNA production of enzymes for p-oxidation in the small intestine of C57BL/6J mice. C57BL/6J male mice, 7 wk old, were fed 5% triacylglyc-erols (TAG low-fat control), 30% TAG + 13% sucrose (high-fat control), 15% DAG + 15% TAG -I- 13% sucrose for 10 d (before obesity development). Values are means SEM, n = 6. P< 0.01, p< 0.001. Abbreviations AGO, acyl-CoA oxidase MCAD, medium-chain acyl-CoA dehydrogenase UCP, uncoupling protein-2 FAT, fatty acid translocase L-FABP, liver fatty acid binding protein.

In both long-chain fatty add oxidation disorders (LCFAOD) and medium-chain fatty acid oxidation disorders (MCAD), emergency management of acute illness and the avoidance of prolonged fasting are key treatment strategies. 

Medium-chain fatty acid (6-12 carbons) oxidation disorders Medium-chain acyl-CoA dehydrogenase deficiency (MCAD)... 

MCAD is responsible for catalysing the first step of p-oxidation of medium chain fatty adds. Although the maximum catalytic activity is attained with... 

Among the fatty acid oxidation disorders, medium-chain acyl-CoA dehydrogenase deficiency (MCAD) is the most common and its frequency is similar to that of phenylketonuria. The disorder can be identified by mutant alleles and some key abnormal metabolites. An A G transition mutation occurs at position 985 of MCAD-cDNA in about 90% of cases. This mutation leads to replacement of lysine with glutamate at position 329 (K329E) of the polypeptide. 

As noted above, there have been reports that link some cases of APLP with a defect in fatty acid metabolism in the fetus. These include fetal deficiencies of long chain 3-hydroxyacyl-coenzyme A dehydrogenase (LCHAD), carnitine-palmitoyl transferase 1 (CPT 1), and medium chain acyl-coenzyme A dehydrogenase (MCAD). The mechanism by which defective fetal fatty acid oxidation causes maternal illness is not known. However, since the fetus uses primarily glucose metabolism for its energy needs, it is likely that toxic products from the placenta, which does use fatty acid oxidation, cause the maternal liver failure. 

Acyl-CoA dehydrogenases (ACADs), flavoproteins found in the mitochondria, are involved in /3-oxidation of fatty acids. Currently, there are five types of ACADs classified according to substrate specificity. Short-chain ACAD (SCAD), medium-chain ACAD (MCAD), long-chain ACAD (LCAD), and very long-chain ACAD... 

Compared with controls, 22 6n-3 biosynthesis was normal in cells from patients with deficiencies of the mitochondrial fatty acid p-oxidation enzymes, vay-long-chain acyl-CoA dehydrogenase (VLCAD) or medium-chain acyl-Co A dehydrogenase (MCAD) (Table 2). These findings confirmed that retro-conversion of 24 6n-3 to 22 6n-3 is via the peroxisomal, but not mitochondrial fatty acid p-oxidation pathway. 

Sometimes a test for more than one protein is needed and mass spectrometry is the method of choice for that purpose. A good example for this would be the use of tandem mass spectrometry to screen neonates for metabolic disorders such as amino acidemias (e.g., phenylketonuria—PKU), organic acidemias (e.g., propionic acidemia—PPA), and fatty acid oxidation disorders (e.g.. Medium-chain acyl-CoA Dehydrogenase deficiency—MCAD) [9]. Although the price of this capital equipment could be high, costs of using it as a sensor is quite low (usually < U.S. 50.00 to screen for more than 20 metabolic disorders), and many states in the United States provide the service to newborns during the first week of life. 

Other genes involved in mitochondrial lipid metabolism, such as acyl-CoA synthetase" or medium-chain acyl-CoA dehydrogenase (MCAD), are also targets of PPAR, indicating that different steps of fatty acid metabolism, like activation, oxidation, and utilization of fatty acids are regulated by the levels of the substrate, the fatty acids. Therefore, we speculated that the main control step in fatty acid P-oxidation, the outer membrane component of carnitine palmitoyltransferase enzyme system, CPT 1, could also be a PPAR target. 

Comparison of the absolute and relative activities obtained with fliese two substrates can often pinpoint the nature of the fatty acid oxidation defect. Medium chain acyl-CoA dehydrogenase deficiency (MCAD) is characterised by a much decreased oxidation of myristate and a high palmitate/myristate (P/M) ratio, mean percentage activity relative to simultaneous controls being 11.5 5.1 (n = 18) with a corresponding P/M ratio of 4.6 1.7 (Fig. 1). 

Medium chain acyl-CoA dehydrogenase (MCAD EC 1.3.99.3) is one of the family of enzymes that catalyse the first of the four reactions that comprise the P-oxidation cycle, the oxidation of fatty acyl-CoA to enoyl-CoA with the insertion of an a-p double bond. MCAD is specific for 6-12 carbon long, straight chain fatty acyl-CoAs. The human enzyme consists of 421 amino acids 25 of which are cleaved upon entry into mitochondria. In the mitochondria, MCAD folding is assisted by heat shock protein 60. Subsequently the monomers are assembled to die active tetramer, incorporating one FAD molecule per subunit. ... 

Gregersen N., Andiesen B.S., Bross P., Bolund L. Kolvraa S. (1994) Disorders of mitochondrial fatty acid oxidation especially medium-chain acyl-CoA dehydrogenase (MCAD) deficiency. In Farriaux J.P. Dhondt J.L. eds New Horizons in Neonatal Screening. Elsevier Science BV, pp 247-55. 

Bross P., Jensen T.G., Krautle E, Winter V., Andresen B.S., Engst S., Bolund L., Kolvraa S, Ghisla S, Rasched 1. Gregersen N. (1992) Characterisation of medium-chain acyl-Co A dehydrogenase (MCAD) with a point mutation associated with MCAD deficiency. In New Developments in Fatty Acid Oxidation, Coates P.M. Tanaka K. eds, pp 473-8. Wiley-Liss, New York. 

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