Abstract：
:3-Methyl-substituted fatty acids are first oxidatively decarboxylated (alpha-oxidation) before they are degraded further via beta-oxidation. We synthesized [1-14C]phytanic and 3-[1-14C]methylmargaric acids in order to study their alpha-oxidation in isolated rat hepatocytes, rat liver homogenates and subcellular fractions. alpha-Oxidation was measured as the production of radioactive CO2. In isolated hepatocytes, maximal rates of alpha-oxidation amounted to 7 and 10 nmol/min x 10(8) cells with phytanic acid and 3-methylmargaric acid, respectively. At equimolar substrate concentrations, alpha-oxidation of branched fatty acids was approximately 10- to 15-fold slower than the beta-oxidation of the straight chain palmitate. In whole liver homogenates, rates of alpha-oxidation that equaled 60 to 70% of those observed in the hepatocytes were obtained. Optimum rates required O2, NADPH, Fe3+, and ATP. Fe3+ could be replaced by Fe2+ and ATP could be replaced by a number of other phosphorylated nucleosides and even inorganic phosphate without loss of activity. NADH could substitute for NADPH but not always with full restoration of activity. A variety of other cofactors and metal ions was either inhibitory or without effect. Scavengers of reactive oxygen species, known to be formed during the NADPH-dependent microsomal reduction of ferric-phosphate complexes, were without effect on alpha-oxidation. No evidence was found for the accumulation of NADPH-dependent or Fe(3+)-dependent reaction intermediates. Subcellular fractionation of liver homogenates demonstrated that alpha-oxidation was located predominantly, if not exclusively, in the endoplasmic reticulum. alpha-Oxidation, measured in microsomal fractions, was not inhibited by CO, cytochrome c, or ferricyanide, indicating that NADPH cytochrome P450 reductase and cytochrome P450 are not involved in alpha-oxidation. Our results indicate that, contrary to current belief, alpha-oxidation is catalyzed by the endoplasmic reticulum. The cofactor requirements suggest that alpha-oxidation involves the reduction of Fe3+ by electrons from NADPH and that it is stimulated by phosphate ions and nucleotides.
journal_name
Arch Biochem Biophysjournal_title
Archives of biochemistry and biophysicsauthors
Huang S,Van Veldhoven PP,Vanhoutte F,Parmentier G,Eyssen HJ,Mannaerts GPdoi
10.1016/0003-9861(92)90565-esubject
Has Abstractpub_date
1992-07-01 00:00:00pages
214-23issue
1eissn
0003-9861issn
1096-0384pii
0003-9861(92)90565-Ejournal_volume
296pub_type
杂志文章abstract：:Proteolysis of glucose dehydrogenase from Bacillus megaterium with proteinase K apparently generated two fragments. The small fragment, designated as K-peptide, was sequenced and its covalent structure was determined as Ser-Ser-Glu-Ala-Ser-Tyr-Val-Thr-Gly-Ile-Thr-Leu-Phe-Ala-Asp-Gly-Gly-Met-Thr- Gln-Tyr-Pro-Ser-Phe-Gl...
journal_title：Archives of biochemistry and biophysics
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journal_title：Archives of biochemistry and biophysics
pub_type： 杂志文章,评审
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journal_title：Archives of biochemistry and biophysics
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journal_title：Archives of biochemistry and biophysics
pub_type： 杂志文章
doi：10.1006/abbi.1994.1385
更新日期：1994-09-01 00:00:00
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journal_title：Archives of biochemistry and biophysics
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journal_title：Archives of biochemistry and biophysics
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journal_title：Archives of biochemistry and biophysics
pub_type： 杂志文章
doi：10.1006/abbi.1996.0380
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journal_title：Archives of biochemistry and biophysics
pub_type： 杂志文章
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journal_title：Archives of biochemistry and biophysics
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journal_title：Archives of biochemistry and biophysics
pub_type： 杂志文章
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journal_title：Archives of biochemistry and biophysics
pub_type： 杂志文章
doi：10.1006/abbi.1993.1290
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journal_title：Archives of biochemistry and biophysics
pub_type： 杂志文章
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journal_title：Archives of biochemistry and biophysics
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journal_title：Archives of biochemistry and biophysics
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更新日期：2013-09-01 00:00:00
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journal_title：Archives of biochemistry and biophysics
pub_type： 杂志文章
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更新日期：2003-12-01 00:00:00
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journal_title：Archives of biochemistry and biophysics
pub_type： 杂志文章
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journal_title：Archives of biochemistry and biophysics
pub_type： 杂志文章
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更新日期：2002-03-15 00:00:00
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journal_title：Archives of biochemistry and biophysics
pub_type： 杂志文章
doi：10.1006/abbi.2000.2043
更新日期：2000-11-15 00:00:00
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journal_title：Archives of biochemistry and biophysics
pub_type： 杂志文章
doi：10.1016/0003-9861(85)90015-3
更新日期：1985-07-01 00:00:00
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journal_title：Archives of biochemistry and biophysics
pub_type： 杂志文章
doi：10.1016/j.abb.2008.07.006
更新日期：2008-10-15 00:00:00
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journal_title：Archives of biochemistry and biophysics
pub_type： 杂志文章
doi：10.1006/abbi.1994.1375
更新日期：1994-08-15 00:00:00
