Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: KEGG:D02011 (FAD)
 5,530 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The metabolism of [14C]pipecolic acid was studied in peroxisomal fractions of rat liver obtained by density gradient centrifugation in Percoll. The production rate of [14CO2] was used to measure the metabolic activity of the fractions towards [14C]carboxypipecolic acid as a substrate. It was shown that this activity was located in the peroxisomal fractions by comparison with the peroxisomal marker enzyme urate oxidase (EC 1.7.3.3). The process was markedly elevated by the addition of FAD. The apparent Km for DL-pipecolic acid was found to be 1.2 mmol L-1. Addition of ATP (1 mmol L-1) did not influence the decarboxylation rate of pipecolic acid. These results might explain the defective metabolism of pipecolic acid in patients with Zellweger syndrome who are lacking peroxisomes.
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PMID:Localization of pipecolic acid metabolism in rat liver peroxisomes: probable explanation for hyperpipecolataemia in Zellweger syndrome. 311 31

Evidence is presented that peroxisomes are more important than other subcellular fractions in rat liver for the final reactions in the biosynthesis of cholic acid from cholesterol. The peroxisomal conversion of 3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta-cholestanoic acid (THCA) into cholic acid was studied in detail and optimal assay conditions were defined. It was shown that the reaction involves intermediary formation of 3 alpha, 7 alpha, 12 alpha, 24-tetrahydroxy-5 beta-cholestanoic acid and that ATP, CoA, Mg++, NAD+ and FAD are necessary. With use of 18O2 and 2H2O it was further shown that the introduction of the 24-hydroxyl group in 3 alpha, 7 alpha, 12 alpha, 24 alpha-tetrahydroxy-5 beta-cholestanoic acid is the combined result of a desaturase and a hydratase. The reaction mechanism is thus analogous to that for beta-oxidation of fatty acids. The role of peroxisomes under conditions in vivo was studied in three patients with the rare inborn cerebro-hepato-renal syndrome of Zellweger. Apparently infants with this fatal disease have a complete lack of peroxisomes in the liver and kidneys. The patients were found to accumulate THCA and various polar metabolites of THCA in serum and bile. Administration of two 3H-labelled C27-precursors to bile acids (5 beta-cholestane-3 alpha, 7 alpha, 12 alpha-triol and 7 alpha-hydroxy-4-cholesten-3-one) resulted in a rapid conversion into THCA and a subsequent slow conversion into cholic acid. Administration of 3H-labelled THCA resulted in a slow conversion into cholic acid.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of peroxisomes in the biosynthesis of bile acids. 386 45

Degradation of the cysteinyl leukotrienes LTE4 and N-acetyl-LTE4, and of LTB4 by beta-oxidation from the omega-end has been recognized as an important pathway in the inactivation of these mediators. The contribution of peroxisomes to leukotriene degradation and inactivation was studied in isolated hepatocytes, in isolated liver peroxisomes, and in patients with inherited peroxisome deficiency. (1) Isolated hepatocytes from rats pretreated with the peroxisome proliferator clofibrate produced highly increased amounts of beta-oxidation products derived from omega-carboxy-LTB4 and omega-carboxy-N-acetyl-LTE4 as compared to normal hepatocytes. (2) Isolated peroxisomes purified from normal and clofibrate-treated liver produced omega-carboxy-dinor-LTB4 and omega-carboxy-tetranor-LTB3 when nucleotide cofactors, including CoA, ATP, NAD+, FAD, and NADPH, were added. beta-Oxidation of the cysteinyl leukotriene omega-carboxy-N-acetyl-LTE4 was observed only with isolated peroxisomes together with a microsome fraction providing an acyl-CoA synthetase activity. (3) Peroxisomal leukotriene-binding proteins were identified by photo-affinity labeling with omega-carboxy-[3H]leukotrienes and precipitation of labeled polypeptides with antibodies against enzymes of the peroxisomal beta-oxidation system. (4) Peroxisomal degradation of leukotrienes in humans was studied by analyses of endogenous leukotrienes and their catabolites in urine from patients with an inherited peroxisomal deficiency disorder (Zellweger syndrome) and healthy infant controls. Urinary LTE4, relative to creatinine, was increased 10-fold in the patients, whereas the beta-oxidation product omega-carboxy-tetranor-LTE3 was only detectable in healthy infants. In addition, LTB4 was exclusively detected in the urine of patients with peroxisome deficiency. The increased levels of biologically active, proinflammatory mediators might be of pathophysiological significance. In addition, the altered pattern of leukotriene metabolites in urine may be of diagnostic value. The measurements in these patients underline the essential role of peroxisomes in the catabolism and inactivation of leukotrienes in humans.
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PMID:Peroxisomal leukotriene degradation: biochemical and clinical implications. 835 7

Cerebronic acid (2-hydroxytetracosanoic acid), an alpha-hydroxy very long-chain fatty acid (VLCFA) and a component of cerebrosides and sulfatides, is unique to nervous tissues. Studies were carried out to identify the pathway and the subcellular site involved in the oxidation of cerebronic acid. The results from these studies revealed that cerebronic acid was catabolized by alpha-oxidation to CO2 and tricosanoic acid (23:0). Studies with subcellular fractions indicated that cerebronic acid was alpha-oxidized in fractions having particulate bound catalase and enzyme systems for the beta-oxidation of VLCFA (e.g., lignoceric acid), suggesting peroxisomes as the subcellular organelle responsible for alpha-oxidation of cerebronic acid. Etomoxir, an inhibitor of mitochondrial fatty acid oxidation, had no effect on cerebronic acid alpha-oxidation. Further, cerebronic acid oxidation was found to be dependent on the presence of NAD+ but not FAD, NADPH, ATP, Mg2+, or CoASH. Intraorganellar localization studies indicated that the enzyme system for the alpha-oxidation of cerebronic acid was associated with the peroxisomal limiting membranes. Studies on cultured fibroblasts from normal subjects and patients with peroxisomal disorders indicated an impairment of alpha-oxidation of cerebronic acid in cell lines that lack peroxisomes [e.g., Zellweger syndrome (ZS)]. On the other hand, alpha-oxidation of cerebronic acid was found to be normal in cell lines from X-linked adrenoleukodystrophy, adult Refsum disease, and rhizomelic chondrodysplasia punctata. Our results clearly demonstrate that alpha-oxidation of alpha-hydroxy VLCFA (cerebronic acid) is a peroxisomal function and that this oxidation is impaired in ZS. Furthermore, this alpha-oxidation enzyme system is distinct from the one for the alpha-oxidation of beta-carbon branched-chain fatty acids (e.g., phytanic acid).
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PMID:Identification of the pathway of alpha-oxidation of cerebronic acid in peroxisomes. 1110 19