+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Peroxisomes and beta-oxidation of long-chain unsaturated carboxylic acids



Peroxisomes and beta-oxidation of long-chain unsaturated carboxylic acids



Scandinavian Journal of Clinical and Laboratory Investigation. Supplementum 204: 33-46



Degradation of unsaturated long-chain carboxylic acids by beta-oxidation, which is a compartmentalized process occurring in both mitochondria and peroxisomes in mammalian cells, was studied using rat liver as a model tissue. Inclusion of (poly)unsaturated fatty acids in the perfusion medium resulted in an increased concentration of catalase-H2O2 complex indicating on-going peroxisomal beta-oxidation. For this to occur, an active peroxisomal delta 3, delta 2-enoyl-CoA isomerase was required for metabolism of the double bonds at odd-numbered positions in acyl-CoA. Experiments with isolated subcellular organelles from rat liver confirmed the presence of isomerase in the peroxisomes, and the enzyme was subsequently isolated with apparent homogeneity. Comparison of amino acid sequences from the enzyme with a published sequence for a bifunctional protein from rat liver identified them representing the same molecule. The peroxisomal bifunctional protein can thus act as a multifunctional hydratase-dehydrogenase-isomerase enzyme. Examination of the mitochondrial isomerase revealed that rat liver mitochondria possess two isoenzymes: a long-chain isomerase not induced by clofibrate-treatment and showing a preference for C10-C12 substrates, and a clofibrate-inducible short-chain isomerase which gave the highest catalytic activity with C6 substrates. Experiments with isolated peroxisomes and unsaturated acyl-CoAs demonstrated that the beta-oxidation of fatty acids having double bonds at even-numbered positions was dependent on 2,4-dienoyl-CoA reductase in peroxisomes, as in mitochondria. Immunocytochemical experiments using the protein A-gold labelling technique, and comparison of their physicochemical properties indicated that all the mammalian reductases purified so far are mitochondrial isoenzymes. It turned out during the isolation of 3-hydroxyacyl-CoA epimerase that there was no monofunctional epimerase at all in the rat liver. Instead, the epimerization reaction occurred via dehydration-hydration catalyzed by two distinct stereospecific hydratases, 2-enoyl-CoA hydratase 1 (the classic hydratase) and 2-enoyl-CoA hydratase 2 (a novel hydratase). The present data demonstrate that peroxisomes contain all the enzymes required for the beta-oxidation of unsaturated fatty acids and support the notion that one of the physiological functions of peroxisomal beta-oxidation is to metabolize long-chain hydrophobic carboxylic acids to shorter, more polar metabolites which are then either metabolized further in the body or excreted.

Please choose payment method:






(PDF emailed within 1 workday: $29.90)

Accession: 040949221

Download citation: RISBibTeXText

PMID: 2042025


Related references

Peroxisomes and β-Oxidation of Long-Chain Unsaturated Carboxylic Acids. Scandinavian Journal of Clinical & Laboratory Investigation 51(Sup204): 33-46, 1991

A direct comparison between peroxisomal and mitochondrial preferences for fatty-acyl beta-oxidation predicts channelling of medium-chain and very-long-chain unsaturated fatty acids to peroxisomes. Biochimica et Biophysica Acta 796(1): 1-10, 1984

Formation of alpha, beta-unsaturated carboxylic acids from amino acids in plant peroxisomes. Phytochemistry 10 (11) 2627-2631, 1971

Differential effect of valproate and its Delta2- and Delta4-unsaturated metabolites, on the beta-oxidation rate of long-chain and medium-chain fatty acids. Chemico-Biological Interactions 137(3): 203-212, 2001

The beta oxidation of di carboxylic acids in isolated mitochondria and peroxisomes. Journal of Inherited Metabolic Disease 6(Suppl. 2): 123-124, 1983

Long-chain acyl-CoA dehydrogenase is a key enzyme in the mitochondrial beta-oxidation of unsaturated fatty acids. Biochimica et Biophysica Acta 1485(2-3): 121-128, 2000

Direct demonstration that the deficient oxidation of very long chain fatty acids in X-linked adrenoleukodystrophy is due to an impaired ability of peroxisomes to activate very long chain fatty acids. Biochemical and Biophysical Research Communications 153(2): 618-624, 1988

Inhibitory effects of some long-chain unsaturated fatty acids on mitochondrial beta-oxidation. Effects of streptozotocin-induced diabetes on mitochondrial beta-oxidation of polyunsaturated fatty acids. Biochemical Journal 230(2): 329-337, 1985

Oxidation of very-long-chain fatty acids in rat brain: cerotic acid is beta-oxidized exclusively in rat brain peroxisomes. Biochimica et Biophysica Acta 1085(3): 381-384, 1991

Long-chain acyl-CoA ester intermediates of beta-oxidation of mono- and di-carboxylic fatty acids by extracts of Corynebacterium sp. strain 7E1C. Biochemical Journal 285: 117-122, 1992

The Conversion of Long Chain Saturated Fatty Acids to their Alpha, Beta-Unsaturated, Beta, Gamma-Unsaturated, and Beta-Hydroxy Derivatives by Enzymes from the Cellular Slime Mold, Dictyostelium Discoideum. Journal of Biological Chemistry 239: 2496-2506, 1964

Analysis of the Alternative Pathways for the beta -Oxidation of Unsaturated Fatty Acids Using Transgenic Plants Synthesizing Polyhydroxyalkanoates in Peroxisomes. Plant Physiology 124(3): 1159-1168, 2000

Analysis of the alternative pathways for the beta-oxidation of unsaturated fatty acids using transgenic plants synthesizing polyhydroxyalkanoates in peroxisomes. Plant Physiology 124(3): 1159-1168, 2000

Accumulation of medium chain acyl-CoAs during beta-oxidation of long chain fatty acid by isolated peroxisomes from rat liver. Biological and Pharmaceutical Bulletin 24(6): 600-606, 2001

Formation of α,β-unsaturated carboxylic acids from amino acids in plant peroxisomes. Phytochemistry 10(11): 2627-2631, 1971