The chemical biology of branched-chain lipid metabolism

• Published in: Progress in Lipid Research 2003-09, Vol.42 (5), p.359-376
• Main Authors: Mukherji, Mridul, Schofield, Christopher J., Wierzbicki, Anthony S., Jansen, Gerbert A., Wanders, Ronald J.A., Lloyd, Matthew D.
• Format: Article
• Language: English
• Subjects: (Very) Long-chain fatty acyl-CoA synthetase; 2-Hydroxyphytanoyl-CoA lyase; Adult Refsum’s disease; Aldehyde dehydrogenase 10; Fatty Acids - chemistry; Fatty Acids - metabolism; Humans; Oxidation-Reduction; Peroxisomal Disorders - metabolism; Peroxisomes - metabolism; Phytanic acid; Phytanic Acid - metabolism; Phytanoyl-CoA 2-hydroxylase; Pristanic acid; Sterol-carrier-protein-2; α-Methylacyl-CoA Racemase
• ISSN: 0163-7827; 1873-2194
• DOI: 10.1016/S0163-7827(03)00016-X

Mammalian metabolism of some lipids including 3-methyl and 2-methyl branched-chain fatty acids occurs within peroxisomes. Such lipids, including phytanic and pristanic acids, are commonly found within the human diet and may be derived from chlorophyll in plant extracts. Due to the presence of a methyl group at its β-carbon, the well-characterised β-oxidation pathway cannot degrade phytanic acid. Instead its α-methylene group is oxidatively excised to give pristanic acid, which can be metabolised by the β-oxidation pathway. Many defects in the α-oxidation pathway result in an accumulation of phytanic acid, leading to neurological distress, deterioration of vision, deafness, loss of coordination and eventual death. Details of the α-oxidation pathway have only recently been elucidated, and considerable progress has been made in understanding the detailed enzymology of one of the oxidative steps within this pathway. This review summarises these recent advances and considers the roles and likely mechanisms of the enzymes within the α-oxidation pathway.