Peroxisomal β‐Oxidation and Polyunsaturated Fatty Acids^a

Abstract

Peroxisomes are capable of oxidizing a variety of substrates including (poly)unsaturated enoyl-CoA esters. The beta-oxidation of unsaturated enoyl-CoA esters in peroxisomes, and also in mitochondria, is not just chain-shortening but also involves the metabolizing of pre-existing carbon-to-carbon double bonds. In addition to the enzymes of the beta-oxidation spiral itself, this metabolism requires the participation of auxiliary enzymes: delta 3, delta 2-enoyl-CoA isomerase; 2,4-dienoyl-CoA reductase; 2-enoyl-CoA hydratase 2 or 3-hydroxyacyl-CoA epimerase; and delta 3,5 delta 2,4-dienoyl-CoA isomerase. Many of these enzymes are present as isoforms, and can be found located in multiple subcellular compartments, for example, peroxisomes, mitochondria or the endoplasmic reticulum, while some of the activities are integral parts of multifunctional enzymes of beta-oxidation systems.

Characterization of PECI, a Novel Monofunctional Δ3,Δ2-Enoyl-CoA Isomerase of Mammalian Peroxisomes

“…These proteins appear to represent a previously unrecognized branch of the hydratase/isomerase superfamily and may lack the active site glutamate residue that has been proposed previously for these enzymes (31,39). However, the significance of these structural differences remain to be determined.…”

“…Previously characterized ⌬ 3 ,⌬ 2 -enoyl-CoA isomerases have been grouped into the hydratase/isomerase superfamily of acylCoA-binding proteins (31,39) and contain the sequence fingerprint VSXINGX 3 AGGXLX 4 CDY (31). However, yeast Eci1p and the mammalian PECI proteins lack this motif (7).…”

“…-enoyl-CoA isomerase, Eci1p, from the yeast S. cerevisiae (7). This apparently monofunctional enzyme is the sole physiologically relevant source of ⌬ 3 ,⌬ 2 -enoyl-CoA isomerase activity in S. cerevisiae and is required to completely oxidize unsaturated fatty acids (7,30,31). Peroxisomes of mammalian cells also contain a ⌬ 3 ,⌬ 2 -enoylCoA isomerase.…”

Molecular Characterization of Saccharomyces cerevisiae Δ3,Δ2-Enoyl-CoA Isomerase

“…-enoyl-CoA isomerases have placed these proteins into the hydratase/isomerase superfamily (8,36). The members of this family catalyze similar transformations on a variety of enoylCoA thioesters (8,36), and some have been shown to possess both isomerase and hydratase activities (37).…”

“…This group of enzymes includes ⌬ 3 ,⌬ 2 -enoyl-CoA isomerase (7,8), ⌬ 3,5 ,⌬ 2,4 -dienoyl-CoA isomerase (9,10), an NADPH-consuming 2,4-dienoyl-CoA reductase (11), and an NADPH-regenerating isocitrate dehydrogenase (12,13) (Fig. 1).…”