The [beta]-oxidation cycle consists of four reactions, catalyzed by acyl-CoA dehydrogenases
(ACADs), enoyl-CoA hydratases, L-3-hydroxyacyl-CoA dehydrogenase, and 3-ketoacyl-CoA thiolase, that sequentially remove two carbons--one acetyl-CoA molecule, until the acyl-CoA is completely converted to acetyl-CoA.
Tanaka, "Purification and characterization of short-chain, medium-chain, and long-chain acyl-CoA dehydrogenases
from rat liver mitochondria.
Selective Inhibition of Acyl-CoA Dehydrogenases
by a Metabolite of Hypoglycin.
In my own specialist area of lipid metabolism, deficiencies of the fatty acid metabolizing acyl-CoA dehydrogenases
are defined as a group of diseases that may be potentially treatable with a combination of dietary manipulation and prevention of fasting, because these are essentially diseases of fasting intolerance.
The first step of the [beta]-oxidation cycle is catalyzed by acyl-CoA dehydrogenases
, whereas the enzymes of MTP catalyze the last 3 steps of [beta]-oxidation.
This is in contrast to the situation for human very long-chain, long-chain, and medium-chain acyl-CoA dehydrogenases
, which are stereospecific for the S-enantiomers only of their methyl branched-chain substrates (24).
Isolated 2-methylbutyrylglycinuria caused by short/branched-chain acyl-CoA dehydrogenase
deficiency: iden tification of a new enzyme defect, resolution of its molecular basis, and evidence for distinct acyl-CoA dehydrogenases
in isoleucine and valine metabolism.
MADD patients showed the whole range of unusual fatty acids observed in both MCAD and vLCAD deficiencies, reflecting the generalized defect of all the mitochondrial acyl-CoA dehydrogenases
. In the neonatal form, there was a strong increase of all these metabolites, whereas in the mild forms of MADD, the increase of [C.sub.10:1] and [C.sub.12:1] was pathognomonic, and the increase of [C.sub.14:2].
In special severe metabolic diseases of [beta]-oxidation, like multiple acyl-CoA dehydrogenase
deficiency (MADD), a direct intake of ketone bodies for energy supply is necessary.
First described in a neonate with hypotonia who subsequently developed a severe pyramidal disorder, EE was initially labeled as a branched-chain acyl-CoA dehydrogenase
ACADM, a member of the acyl-CoA dehydrogenase
(ACAD) family that comprises 9 known proteins, is involved in the oxidation of medium-chain fatty acids and amino acids (Kim Miura, 2004).
The four enzymes making up this pathway, in the order that they are utilized, are: (a) an acyl-CoA dehydrogenase
, (b) a 2,3-encyl-CoA hydratase, (c) an L-3-hydroxyacyl-CoA dehydrogenase, and (d) a 3-ketoacyl-CoA thiolase.