Publications

• Regulation of the biosynthesis of 4,7,10,13,16,19-docosahexaenoic acid.

  Luthria D.L., Mohammed B.S., Sprecher H.

  The synthesis of 4,7,10,13,16,19-docosahexaenoic acid (22:6(n-3)) requires that when 6,9,12,15,18,21-tetracosahexaenoic acid (24:6(n-3)) is produced in the endoplasmic reticulum, it preferentially moves to peroxisomes for one cycle of beta-oxidation rather than serving as a substrate for membrane ... >> More

  The synthesis of 4,7,10,13,16,19-docosahexaenoic acid (22:6(n-3)) requires that when 6,9,12,15,18,21-tetracosahexaenoic acid (24:6(n-3)) is produced in the endoplasmic reticulum, it preferentially moves to peroxisomes for one cycle of beta-oxidation rather than serving as a substrate for membrane lipid synthesis. Both 24:6(n-3) and its precursor, 9,12,15,18,21-tetracosapentaenoic acid (24:5(n-3)), were poor substrates for acylation into 1-acyl-sn-glycero-3-phosphocholine (1-acyl-GPC) by rat liver microsomes. When peroxisomes were incubated with 1-14C- or 3-14C-labeled 7,10,13,16,19-docosapentaenoic acid (22:5(n-3)), [1-14C]22:6(n-3), [3-14C]24:5(n-3), or [3-14C]24:6(n-3), only small amounts of acid-soluble radioactivity were produced when double bond removal at positions 4 and 5 was required. When microsomes and 1-acyl-GPC were included in incubations, the preferred metabolic fate of acids, with their first double bond at either positions 4 or 5, was to move out of peroxisomes for esterification into the acceptor rather than serving as substrates for continued beta-oxidation. When [1-14C]22:6(n-3) or [3-14C]24:6(n-3) was incubated with peroxisomes, 2-trans-4,7,10,13,16,19-22:7 accumulated. The first cycle of 20:5(n-3) beta-oxidation proceeds through 2-trans-4,8,11,14,17-20:6 and thus requires both Delta3,5,Delta2, 4-dienoyl-CoA isomerase and 2,4-dienoyl-CoA reductase. The accumulation of the substrate for 2,4-dienoyl-CoA reductase, as generated from 22:6(n-3), but not from 20:5(n-3), suggests that this enzyme distinguishes between subtle structural differences. When 22:6(n-3) is produced from 24:6(n-3), its continued degradation is impaired because of low 2,4-dienoyl-CoA reductase activity. This slow reaction rate likely contributes to the transport of 22:6(n-3) out of peroxisomes for rapid acylation into 1-acyl-GPC by microsomes. << Less

  J Biol Chem 271:16020-16025(1996) [PubMed] [EuropePMC]

• Characterisation of human peroxisomal 2,4-dienoyl-CoA reductase.

  De Nys K., Meyhi E., Mannaerts G.P., Fransen M., Van Veldhoven P.P.

  Based on the primary structure of the rat peroxisomal 2,4-dienoyl-CoA reductase (M. Fransen, P.P. Van Veldhoven, S. Subramani, Biochem. J. 340 (1999) 561-568), the cDNA of the human counterpart was cloned. It contained an open reading frame of 878 bases encoding a protein of 291 amino acids (calcu ... >> More

  Based on the primary structure of the rat peroxisomal 2,4-dienoyl-CoA reductase (M. Fransen, P.P. Van Veldhoven, S. Subramani, Biochem. J. 340 (1999) 561-568), the cDNA of the human counterpart was cloned. It contained an open reading frame of 878 bases encoding a protein of 291 amino acids (calculated molecular mass 30778 Da), being 83% identical to the rat reductase. The gene, encompassing nine exons, is located at chromosome 16p13. Bacterially expressed poly(His)-tagged reductase was active not only towards short and medium chain 2,4-dienoyl-CoAs, but also towards 2,4,7,10,13,16,19-docosaheptaenoyl-CoA. Hence, the reductase does not seem to constitute a rate limiting step in the peroxisomal degradation of docosahexaenoic acid. The reduction of docosaheptaenoyl-CoA, however, was severely decreased in the presence of albumin. << Less

  Biochim. Biophys. Acta 1533:66-72(2001) [PubMed] [EuropePMC]

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