Mammalian mitochondrial β-oxidation

Abstract

The enzymic stages of mammalian mitochondrial beta-oxidation were elucidated some 30-40 years ago. However, the discovery of a membrane-associated multifunctional enzyme of beta-oxidation, a membrane-associated acyl-CoA dehydrogenase and characterization of the carnitine palmitoyl transferase system at the protein and at the genetic level has demonstrated that the enzymes of the system itself are incompletely understood. Deficiencies of many of the enzymes have been recognized as important causes of disease. In addition, the study of these disorders has led to a greater understanding of the molecular mechanism of beta-oxidation and the import, processing and assembly of the beta-oxidation enzymes within the mitochondrion. The tissue-specific regulation, intramitochondrial control and supramolecular organization of the pathway is becoming better understood as sensitive analytical and molecular techniques are applied. This review aims to cover enzymological and organizational aspects of mitochondrial beta-oxidation together with the biochemical aspects of inherited disorders of beta-oxidation and the intrinsic control of beta-oxidation.

Role of ERAB/l-3-Hydroxyacyl-coenzyme A Dehydrogenase Type II Activity in Aβ-induced Cytotoxicity

“…1.1.1.35) (17,18), a participant in the third reaction of the fatty acid ␤-oxidation spiral (19,20). This identification is consistent with a recent report concerning properties of a human L-3-hydroxyacyl-CoA dehydrogenase (21), the cDNA sequence of which is identical to that of human ERAB.…”

“…This identification is consistent with a recent report concerning properties of a human L-3-hydroxyacyl-CoA dehydrogenase (21), the cDNA sequence of which is identical to that of human ERAB. 2 Although consequences of ERAB/HADH II deficiency are not known, heritable disorders with defects in fatty acid ␤-oxidation have been identified (19,20). These patients have hepatomegaly, cardiomegaly, encephalopathies, peripheral neuropathy, rhabdomyolysis, and myoglobinuria, suggesting a role for fatty acid ␤-oxidation enzymes in the metabolic balance of a range of organs.…”

Deorphanization of GPR109B as a Receptor for the β-Oxidation Intermediate 3-OH-octanoic Acid and Its Role in the Regulation of Lipolysis

“…In contrast, 3-OH fatty acids are produced during ␤-oxidation of fatty acids in various mammalian tissues (3). Under basal conditions, the plasma concentrations of 3-hydroxylated medium-chain fatty acids are below 0.4 M (24, 28).…”

“…The net rate of lipolysis is increased during fasting or periods of increased energy demand. Fatty acids generated via lipolysis undergo ␤-oxidation in the muscle and liver to serve directly as a source of energy or as a precursor for ketone bodies (3). The major intracellular regulator of lipolysis is cyclic AMP, which stimulates cAMPdependent kinase to activate lipolytic enzymes (2, 4 -6).…”

A Defect in β-Oxidation Causes Abnormal Inflorescence Development in Arabidopsis

“…Plants are able to degrade fatty acids completely within their peroxisomes, whereas animals require an additional mitochondrial ␤ -oxidation system because the peroxisomal ␤ -oxidation system seems to function only as a chain-shortening system (Tolbert, 1981;Mannaerts and Debeer, 1982;Gerhardt, 1986). The ␤ -oxidation systems in animals have been well characterized both molecularly and biochemically (reviewed in Kunau et al, 1995;Eaton et al, 1996;Hashimoto, 1996;Mannaerts and van Veldhoven, 1996).…”