Disease relevance of pristanic acid

• It is shown that in generalized peroxisomal disorders, the absolute concentrations of 2,3-pristenic acid, 3-hydroxypristanic acid, and 3-ketopristanic acid were comparable to those in the controls, whereas relative to the pristanic acid concentrations these intermediates were significantly decreased [1].
• In the blood spot from a patient with rhizomelic chondrodysplasia punctata, the concentration of phytanic acid was increased, whereas pristanic acid was within the control range, resulting in a low pristanic acid/phytanic acid ratio [2].
• Phytanic acid accumulated in plasma from the Refsum's disease patient [649 mumol/L, controls > 1 y (n = 100): < 10 mumol/L], whereas the pristanic acid concentration was within the control range [1.4 mumol/L, controls > 1 y (n = 100): < 3 mumol/L] [3].
• In livers from patients with the cerebro-hepato-renal syndrome of Zellweger, a genetic disease characterized by the absence of morphologically distinguishable peroxisomes, pristanic acid oxidase activity was found to be deficient [4].
• Biochemical investigations revealed typical features of Niemann-Pick disease type C. In addition, there was evidence of defective peroxisomal beta-oxidation of branched-chain substrates (3 alpha, 7 alpha, 12 alpha-trihydroxycholestanoic acid and pristanic acid) [5].

High impact information on pristanic acid

• Oxidation of pristanic acid in fibroblasts and its application to the diagnosis of peroxisomal beta-oxidation defects [6].
• Pristanic acid oxidation measurements proved a reliable tool for assessing complementation in fused heterokaryons from patients with peroxisomal biogenesis defects [6].
• Peroxisomes are organelles that function in the beta-oxidation of long- and very long-chain acyl-CoAs, bile acid-CoA intermediates, prostaglandins, leukotrienes, thromboxanes, dicarboxylic fatty acids, pristanic acid, and xenobiotic carboxylic acids [7].
• Under the conditions used, the apoptosis-promoting effect of BCFAs was neither shared by saturated or unsaturated straight chain fatty acids nor by artificial peroxisome proliferators, which, like phytanic and pristanic acid, have been shown to activate the peroxisome proliferator-activated receptor alpha (PPARalpha) [8].
• Here we show that phytanic and pristanic acid, two BCFAs that are metabolized in peroxisomes, promote apoptosis in cultured vascular smooth muscle cells of human, rat, and porcine origin [8].

Chemical compound and disease context of pristanic acid

• Concentrations of phytanic acid and pristanic acid were measured in stored dried blood spots collected at neonatal screening from patients with peroxisomal disorders, and compared with concentrations in control blood spots [2].

Biological context of pristanic acid

• METHODS: Multiple peroxisomal functions including de novo plasmalogen synthesis, dihydroxyacetonephosphate acyltransferase (DHAPAT) activity, C26:0/C22:0 ratio, C26:0 and pristanic acid beta-oxidation, and phytanic acid alpha-oxidation were analyzed in fibroblasts from a series of patients with defined clinical phenotypes [9].
• The phytol derivatives phytanic acid and pristanic acid may activate nuclear hormone receptors and influence gene expression and cell differentiation [10].
• The three biochemical markers measured in fibroblasts (DHAPAT activity, C26:0 beta-oxidation and pristanic acid beta-oxidation) also correlated with the genotypes [11].
• Genetic heterogeneity in patients with a disorder of peroxisomal beta-oxidation: a complementation study based on pristanic acid beta-oxidation suggesting different enzyme defects [12].

Anatomical context of pristanic acid

• Isoprenoid (branched) fatty acids such as pristanic acid can be degraded via beta-oxidation in peroxisomes [13].
• Biochemically, these disorders are characterized by accumulation of phytanic and/or pristanic acid in tissues and body fluids [14].
• Furthermore, peroxisomal beta-oxidation substrates, such as very-long-chain fatty acids and pristanic acid, accumulated in the testis, whereas the concentration of docosapentaenoic acid, a polyunsaturated fatty acid and peroxisomal beta-oxidation product, was reduced [15].
• However, the effects of phytanic acid were not mediated by its alpha-oxidation product pristanic acid, which did not promote brown adipocyte differentiation or stimulate transcription of the uncoupling protein-1 gene [10].
• To identify potential AMACR-regulating factors, we treated LNCaP cells (an androgen-responsive CaP-derived cell line) and NPrEC cells (a normal prostate basal epithelial cell line) with increasing concentrations of pristanic acid, phytanic acid, 5alpha-dihydrotestosterone, and 17beta-estradiol [16].

Associations of pristanic acid with other chemical compounds

• The relationship between peroxisomal and mitochondrial oxidation of the methyl branched fatty acids, phytanic acid and pristanic acid, was studied in normal and mutant human skin fibroblasts with established enzyme deficiencies [17].
• Patients with a deficiency of alpha-methylacyl-CoA racemase accumulate in their plasma pristanic acid and the bile acid intermediates di- and trihydroxycholestanoic acid, which are all substrates of the peroxisomal beta-oxidation system [18].
• This implies that phytanoyl-CoA is synthesized on the cytoplasmic surface of peroxisomal membrane and is translocated through the membrane for its alpha-oxidation to pristanic acid in the matrix of peroxisomes [19].
• Phytanic acid, but not pristanic acid, mediates the positive effects of phytol derivatives on brown adipocyte differentiation [10].
• Defective oxidation of pristanic acid by fibroblasts from patients with disorders in propionic acid metabolism [20].

Gene context of pristanic acid

• Branched-chain fatty acids (such as phytanic and pristanic acid) are ligands for the nuclear hormone receptor peroxisome proliferator-activated receptor alpha (PPARalpha) in vitro [21].
• Recently, gene targeting of the SCP2/SCPx gene has shown in mice that the SCPx beta-ketothiolase is involved in peroxisomal beta-oxidation of 2-methyl-branched chain fatty acids like pristanic acid [22].
• A fairly good correlation was found for pristanic acid beta-oxidation, but the best correlation was found for DHAPAT activity and C26:0 beta-oxidation [9].
• Here we show that both phytanic acid and pristanic acid activate the peroxisome proliferator-activated receptor alpha (PPARalpha) in a concentration-dependent manner [23].
• We investigated the role of microsomal fatty aldehyde dehydrogenase (FALDH) in the conversion of pristanal into pristanic acid [24].

Analytical, diagnostic and therapeutic context of pristanic acid

• Phytanic acid, pristanic acid, and very-long-chain fatty acid methyl esters measured simultaneously by capillary gas chromatography [25].
• Separation of phytanic and pristanic acid by high-pressure liquid chromatography: application of the method [26].
• The synthesis of pristanic acid from phytanic acid, and a simple reversed-phase high-pressure liquid chromatographic (HPLC) method for the separation and purification of these acids, is described [26].
• On the basis of competition experiments and immunoprecipitation studies using antibodies raised against rat liver microsomal long-chain fatty acyl-CoA synthetase (EC 6.2.1.3) we conclude that pristanic acid is activated by the same enzyme which activates long-chain fatty acids, i.e., long-chain fatty acyl-CoA synthetase [27].
• No epimerization at the 2-methyl carbon of pristanic acid and its methyl or (--) menthyl esters was detected after treatment in 1N aqueous or methanolic NaOH under reflux for 1 hr or at 120 degrees (sealed tube) for 24 hr [28].

References