Beta-oksidation, alfa-oksidation ja isopreenirakenteet . AMACR geeni , alfa-metyyli-Coa Rasemaasi, koliininmuodostuksessa tärkeä kohta

 https://pubmed.ncbi.nlm.nih.gov/11893780/

. 2002 Mar;43(3):438-44.

Stereochemistry of the peroxisomal branched-chain fatty acid alpha- and beta-oxidation systems in patients suffering from different peroxisomal disorders

S Ferdinandusse 1, H Rusch, A E M van Lint, G Dacremont, R J A Wanders, P Vreken

Affiliations

• PMID: 11893780

Free articleAbstract

Phytanic acid (3,7,11,15-tetramethylhexadecanoic acid) is a branched-chain fatty acid derived from dietary sources and broken down in the peroxisome to pristanic acid (2,6,10,14-tetramethylpentadecanoic acid) via alpha-oxidation. Pristanic acid then undergoes beta-oxidation in peroxisomes. Phytanic acid naturally occurs as a mixture of (3S,7R,11R)- and (3R,7R,11R)-diastereomers. In contrast to the alpha-oxidation system, peroxisomal beta-oxidation is stereospecific and only accepts (2S)-isomers. Therefore, a racemase called alpha-methylacyl-CoA racemase is required to convert (2R)-pristanic acid into its (2S)-isomer. To further investigate the stereochemistry of the peroxisomal oxidation systems and their substrates, we have developed a method using gas-liquid chromatography-mass spectrometry to analyze the isomers of phytanic, pristanic, and trimethylundecanoic acid in plasma from patients with various peroxisomal fatty acid oxidation defects. In this study, we show that in plasma of patients with a peroxisomal beta-oxidation deficiency, the relative amounts of the two diastereomers of pristanic acid are almost equal, whereas in patients with a defect of alpha-methylacyl-CoA racemase, (2R)-pristanic acid is the predominant isomer. Furthermore, we show that in alpha-methylacyl-CoA racemase deficiency, not only pristanic acid accumulates, but also one of the metabolites of pristanic acid, 2610-trimethylundecanoic acid, providing direct in vivo evidence for the requirement of this racemase for the complete degradation of pristanic acid.

• https://www.sciencedirect.com/science/article/abs/pii/S1096719217302378?via%3Dihub

https://www.genecards.org/search/results?q=alpha-methylacyl-CoA+racemase%2c

GeneCards Summary(1 record)

• GeneCards: AMACR encodes alpha-methylacyl-CoA racemase, an enzyme that converts pristanoyl-CoA and C27-bile acyl-CoAs between their (R)- and (S)-stereoisomers. This reaction is required for degradation of these substrates by peroxisomal beta-oxidation. The protein functions in metabolic pathways linked to bile acid biosynthesis and fatty acid metabolism. The encoded enzyme localizes to the mitochondrion, peroxisome, cytoplasm, and plasma membrane, placing it at the center of intracellular lipid handling. Its activity is associated with catalytic function and binding, and tissue expression is high in the respiratory system and renal system, with substantial expression in the hepatobiliary system and proximal digestive tract. Read-through transcription also exists between AMACR and the upstream neighboring C1QTNF3 gene. Pathogenic variants in AMACR are reported in congenital bile acid synthesis defect type 4 and alpha-methylacyl-CoA racemase deficiency. Mutations in AMACR have also been associated with adult-onset sensorimotor neuropathy, pigmentary retinopathy, and adrenomyeloneuropathy due to defects in bile acid synthesis.
• Alias: Alpha-Methylacyl-CoA Racemase
• Alias: 2-Methylacyl-CoA Racemase
• NCBI Gene: This gene encodes a racemase. The encoded enzyme interconverts pristanoyl-CoA and C27-bile acylCoAs between their (R)- and (S)-stereoisomers. The conversion to the (S)-stereoisomers is necessary for degradation of these substrates by peroxisomal beta-oxidation. Encoded proteins from this locus localize to both mitochondria and peroxisomes. Mutations in this gene may be associated with adult-onset sensorimotor neuropathy, pigmentary retinopathy, and adrenomyeloneuropathy due to defects in bile acid synthesis. Alternatively spliced transcript variants have been described. Read-through transcription also exists between this gene and the upstream neighboring C1QTNF3 (C1q and tumor necrosis factor related protein 3) gene. [provided by RefSeq, Mar 2011]
• Molecular Function(3 records)
  • alpha-methylacyl-CoA racemase,expressed in liver,peroxisomal,converting pristanoyl-CoA and C27 beta acyl-CoA to their (5) stereoisomers,essential step for the formation of cholic acid by the normal peroxisomal pathway (GENATLAS)
  • Acts only on coenzyme A thioesters, not on free fatty acids, and accepts as substrates a wide range of alpha-methylacyl-CoAs, including pristanoyl-CoA, trihydroxycoprostanoyl-CoA (an intermediate in bile acid synthesis), and arylpropionic acids like the anti-inflammatory drug ibuprofen (2-(4-isobutylphenyl)propionic acid) but neither 3-methyl-branched nor linear-chain acyl-CoAs. (UniProtKB/TrEMBL)
  • Disorder(2 records)
    • Alpha-Methylacyl-Coa Racemase Deficiency Gene-disease relationship from OMIM®, UniProtKB/Swiss-Prot, ClinVar and three more
      Aliases:

      Alpha-Methylacyl-Coa Racemase Deficiency
      Symptoms:

      reduced alpha-methylacyl-coa racemase activity in cultured fibroblasts
      Summaries:

      • Alpha-methylacyl-CoA racemase (AMACR) deficiency is a disorder that causes a variety of neurological problems that begin in adulthood and slowly get worse. People with AMACR deficiency may have a gradual loss in intellectual functioning (cognitive decline), seizures, and migraines. They may also have acute episodes of brain dysfunction (encephalopathy) similar to stroke, involving altered consciousness and areas of damage (lesions) in the brain. Other features of AMACR deficiency may include weakness and loss of sensation in the limbs due to nerve damage (sensorimotor neuropathy), muscle stiffness (spasticity), and difficulty coordinating movements (ataxia). Vision problems caused by deterioration of the light-sensitive layer at the back of the eye (the retina) can also occur in this disorder.
    • Bile Acid Synthesis Defect, Congenital, 4 Gene-disease relationship from OMIM®, UniProtKB/Swiss-Prot, ClinVar and two more
      Aliases:

      • 2-Methylacyl-Coa Racemase Deficiency
      • Alpha-Methyl-Acyl-Coa Racemase Deficiency
      • Alpha-Methylacyl-Coa Racemase Deficiency