Medium chain fatty acid:coenzyme

Diagnosis of medium-chain acyl-coenzyme A dehydrogenase deficiency in the neonatal period by measurement of medium-chain fatty acids in plasma and filter paper blood samples. 

The synthesis of fatty acids for incorporation into milk fat within the mammary gland is similar to that seen in other tissues. There are two basic reactions the conversion of acetyl-coenzyme A (CoA) to malonyl-CoA, followed by incorporation of the latter into a growing acyl chain via the action of the fatty acid-synthetase complex. However, the product of these reactions in lactating mammary tissue from many species is short and medium chain fatty acids. In most other tissues the product is palmitate. For more complete details see Moore and Christie, (1978), Bauman and Davis (1974), and Patton and Jensen (1976). 

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 ... 

Fatty acyl-CoA ligases (specific for short, medium, or long chain fatty acids) catalyze formation of fatty acyl thioester conjugate with coenzyme A (Diagram)... 

It is, however, better known that flavoenzymes (i.e., enzymes utilizing the flavin adenine dinucleotide [FAD FADH2] redox system) mediate the introduction of a,P carbon-carbon double bonds into carboxylic acids and into acetyl Coenzyme A (acetyl CoA) thioesters of long-, medium-, and short-chain fatty acids. In carboxylic acids, such as those of the tricarboxylic acid (citric acid, TCA, or Krebs) cycle (Chapter 11) the oxidation is affected by the enzyme sucdnate dehydrogenase (fumerate reductase— EC 1.3.99.1), which utilizes the cofactor flavin adenine dinucleotide (FAD) The latter is reduced to FADH2 and an ( )-double bond is introduced. The process shown in Scheme 9.105, for the conversion of succinate (1,4-butanedioic acid) to fumerate [(E)-l,4-butenedioic acid], is a fragment of the tricarboxylic acid (citric acid, TCA, or Krebs) cycle (Chapter 11), which is the pathway commonly utilized for oxidative degradation of acetate to carbon dioxide. 

Interestingly, when the dehydrogenation of coenzyme-bound thioester (Scheme 8.70, et se )—in the growing chain of acetyl CoA thioesters of long-, medium-, and short-chain fatty acids generated in the polyketide synthase cassette of reactions— occurs, it still appears that the FAD. FADH cofactor is involved, but there are... 

Kamijo T, Indo Y, Souri M, Aoyama T, Hara T, Yamamoto S et al. Medium chain 3-ketoacyl-coenzyme A thiolase deficiency a new disorder of mitochondrial fatty acid beta-oxidation. Pediatr Res 1997 42 569-576. 

Thiolester hydrolases (EC 3.1.2) play an important role in the biochemistry of lipids. They catalyze the hydrolysis of acyl-coenzyme A thiolesters of various chain lengths to free fatty acids and coenzyme A. The current list of over 20 specific enzymes includes acetyl-CoA hydrolase (EC 3.1.2.1), pal-mi toy 1-Co A hydrolase (EC 3.1.2.2), and an acyl-CoA hydrolase (EC 3.1.2.20) of broad specificity for medium- to long-chain acyl-CoA [128],... 

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,...

In laying hens, induction of this riboflavin protein results in a 100-fold increase in plasma riboflavin, compared with males or nonlaying females. In mutant chickens lacking the protein, the adult has massive urinary loss of riboflavin. The embryo develops normally for about 10 days, then develops severe hypoglycemia associated with a reduction in medium-chain acyl coenzyme A (CoA) dehydrogenase to 20% of normal activity and the accumulation of intermediates of fatty acid oxidation (White, 1996). 

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. 

He, X.-Y., Yang, S.-Y. Schulz, H. ( 992)Arch. Biochem. Biophys. 298, 527-531. Inhibition ofenoyl-CoA hydratase by long-chain L-3-hydroxyacyl-CoA and its possible effect on fatty acid oxidation. Powell, P.J., Lau, S.M., Killian, D. Thorpe, C. (1987) Biochem. 26, 3704-3710. Interaction of acyl coenzyme A substrates and analogues with pig kidney medium-chain acyl-CoA dehydrogenase. 

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