Disease relevance of hexacosanoic acid

• We therefore measured the plasma concentrations of very-long-chain saturated fatty acids in eight patients with adrenal insufficiency; of these, five had elevated plasma hexacosanoic acid concentrations (range, 2.42 to 6.43 mumol per liter; mean normal level [+/- SD], 0.83 +/- 0.45), confirming the presence of adrenomyeloneuropathy [1].
• Cultured skin fibroblasts and plasma from patients with the infantile, but not the adult, disorder show marked increases in the concentration of the long-chain fatty acid, hexacosanoic acid (C26), a feature once thought pathognomonic of adrenoleukodystrophy or Zellweger's syndrome [2].
• However, INH treatment of Mycobacterium tuberculosis causes the accumulation of hexacosanoic acid (C(26:0)), a result unexpected for the blocking of an enoyl-reductase [3].
• X-linked adrenoleukodystrophy (X-ALD) is a peroxisomal disorder biochemically characterized by the accumulation of very long chain fatty acids (VLCFA), particularly hexacosanoic acid (C(26:0)) and tetracosanoic acid (C(24:0)), in tissues and biological fluids [4].
• The inhibition zones of isolated terpenoids were also recorded and the activity index was calculated and it was found that hexacosane was more active (IZ = 13.39) against E. coli and hexacosanoic acid had greater activity against A. flavus (IZ = 11.56) [5].

High impact information on hexacosanoic acid

• In this study we demonstrate fivefold or greater increases of very-long-chain fatty acid levels, particularly hexacosanoic acid (C26:0) and hexacosenoic acid (C26:1), in plasma and cultured skin fibroblasts from 20 patients [6].
• In response to INH treatment, saturated hexacosanoic acid (C26:0) accumulated on a 12-kilodalton acyl carrier protein (AcpM) that normally carried mycolic acid precursors as long as C50 [7].
• Adrenoleukodystrophy (ALD) is an inherited disorder of fatty acid metabolism marked by accumulation of very long chain saturated fatty acids (VLCFA), especially the 26-carbon acid, hexacosanoic acid (HA), in membranes and tissues [8].
• By complementing the homologous yeast mutants, we found that Ssc1 could rescue normal sphingolipid synthesis in the sur4/elo3 mutant lacking the ability to synthesize cerotic acid (C(26:0)) [9].
• It is associated with the accumulation of saturated very-long-chain fatty acids (VLCFAs), such as hexacosanoic acid (C26:0), that occurs as a result of the impaired capacity to degrade these substances, a reaction that normally takes place in the peroxisome [10].

Biological context of hexacosanoic acid

• The content of hexacosanoic acid (C26:0), tetracosanoic acid (C24:0) and docosanoic acid (C22:0) in adrenoleukodystrophy (ALD) hemizygotes and heterozygotes was significantly higher than in controls [11].

Anatomical context of hexacosanoic acid

• The ratio of hexacosanoic acid (C26:0) to docosanoic acid (C22:0) in erythrocyte membrane sphingomyelin from ALD patients was 2.6-fold higher than that of the controls [12].
• Free radical release in C6 glial cells enriched in hexacosanoic acid: implication for X-linked adrenoleukodystrophy pathogenesis [13].
• Hexadecanoic and tuberculostearic acids were identified as the major cell wall fatty acids by gas-liquid chromatographic analysis; hexacosanoic acid was the major mycolic acid cleavage product, and 2-eicosanol was the major alcohol [14].
• The prenatal diagnosis of adrenoleukodystrophy. Demonstration of increased hexacosanoic acid levels in cultured amniocytes and fetal adrenal gland [15].
• We have investigated the palmitic acid (C16:0) and cerotic acid (C26:0) activating activities in rat-liver microsomes and peroxisomes [16].

Associations of hexacosanoic acid with other chemical compounds

• In postmortem human control and adrenoleukodystrophy brains, the esterifying activity toward cerotic acid was on the average 25% of that toward oleic acid [17].
• The beta-oxidation of lignoceric acid (C24:0), hexacosanoic acid (C26:0), and their coenzyme A derivatives was investigated in human skin fibroblast homogenates [18].
• We identified three fatty acids as cis-16-pentacosenoic acid (C25:1), cis-17-hexacosenoic acid (C26:1), and hexacosenoic acid (C26:1), and hexacosanoic acid (C26:0) by gas chromatography-mass spectrometry [19].
• Further fractionation of the glycerophospholipids by high performance liquid chromatography showed a significant (up to 39-fold) accumulation of hexacosanoic acid (C26:0) in phosphatidylcholine, but not in other phosphatidyl derivatives [20].
• C 26:0/C 22:0 ratio can be experimentally increased in serum of normal rats by oral administration of hexacosanoic acid (C 26:0) or of thioridazine, an inhibitor of peroxisomal beta-oxidation [21].

Gene context of hexacosanoic acid

• VLCFAs did not affect the expression of gp91phox or p22phox whereas the mRNA and protein levels of p47phox were significantly (two or three-fold) increased following treatment of fibroblasts with lignoceric acid or cerotic acid [22].
• Increased concentrations of hexacosanoic acid (C26:O) were consistently found in the Zellweger syndrome [23].

Analytical, diagnostic and therapeutic context of hexacosanoic acid

• The most consistently observed increase is that in hexacosanoic acid (C26:0); thus, measurement of plasma C26:0 concentration by gas-liquid chromatography provides a rapid, sensitive method of diagnosis [24].

References