Abstract
Fatty acids with from 24 to 28 carbon atoms (very long-chain fatty acids, VLCFA) are present in small amounts in all mammalian tissues. Even longer chain fatty acids with from 30 to 38 carbon atoms (ultra-long-chain fatty acids, ULCFA) are found in certain specialized tissues including retina, brain, and spermatozoa. In patients with inherited defects in peroxisomal structure and/or function, there is an accumulation of VLCFA in most tissues, while VLCFA and ULCFA levels are increased in brain. The most pronounced changes occur in those patients who have defects in peroxisomal assembly (Zellweger syndrome, infantile Refsumts disease, and neonatal adrenoleukodystrophy). In the brain of these individuals, ULCFA are distributed largely in molecular species of phosphatidylcholine with penta-, hexa-, and heptaenoic acids. In contrast, patients with X-linked adrenoleukodystrophy have increased levels of phosphatidylcholine with monoenoic rather than polyenoic ULCFA. A defect in a peroxisomal VLCFA CoA synthetase or ligase has been reported for these patients, but assembly of their peroxisomes is apparently normal.
We speculate that ULCFA are normal products of carbon chain elongation. We have confirmed this by demonstrating the elongation of [1-14C]hexacosatetraenoic acid (26:4n-6) by rat brain in vivoto a series of longer chain tetraenoic acids with carbon chain lengths up to 34. Elongation to ULCFA can occur as well in non-neural tissues as shown by detection of labeled saturated and monoenoic fatty acids with up to 32 carbon atoms after incubation of normal and Zellweger syndrome fibroblasts with [2-14C] acetate. Increased labeling of VLCFA and ULCFA is observed in cells from patients with peroxisomal disorders.
Our data suggest that ULCFA with up to at least 32 carbon atoms are formed normally, as a part of the elongation process in most mammalian tissues, and that control of carbon chain elongation is a major function of peroxisomes. Impairment of this function as occurs in peroxisomal disease results in the accumulation of VLCFA and ULCFA. The relative enrichment in normal tissues of ULCFA such as 32:6n-3 in ram and bull spermatozoa and 36:4n-6 in human and rat brain suggests a probable physiological role for this class of fatty acids in these tissues.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Aveldaño M and Sprecher H (1987) Very long-chain (C24-C36) polyenoic fatty acids of the n-3 and n-6 series in dipolyunsaturated phosphatidylcholines from bovine retina. J Biol Chem 262: 1180–1186.
Bligh BG and Dyer WJ (1959) A rapid method of total lipid extraction and purification, Can J Biochem Physiol 37: 911–917.
Johnson DW (1990) A synthesis of unsaturated very long-chain fatty acids. Chem Phys Lipids 56: 65–71.
Johnson DW, Beckman K, Robinson BS, Fellenberg AF, Poulos A (in press). Monoenoic fatty acids in human brain: Isomer identification and distribution. Lipids.
Lazo O, Contreras M, Bhushan A, Stanley W, Singh I (1989) Adrenoleukodystrophy: Impaired oxidation of fatty acids due to peroxisomal lignoceroyl-CoA ligase deficiency. Arch Biochem Biophys 270: 722–728.
Naughton JM (1981) Supply of polyenoic fatty acids to the mammalian brain: The ease of conversion of the short chain fatty acids to their longer chain polyunsaturated metabolites in liver, brain, placenta and blood. Int J Biochem 13: 21–32.
Poulos A, Sharp P, Johnson DW (1989) Polyenoic very long-chain fatty acids in peroxisomal disease. Biochemical discrimination of Zellweger’s syndrome from other phenotypes. Neurology 39: 44–47.
Poulos A, Sharp P, Johnson DW, Easton C (1988) The occurrence of polyenoic very long chain fatty acids with greater than 32 carbon atoms in molecular species of phosphatidylcholine in normal and peroxisome-deficient (Zellweger’s syndrome) brain. Biochem J 253: 645–650.
Poulos A, Sharp P, Johnson D, White IG, Fellenberg A (1986a) The occurrence of polyenoic fatty acids with greater than 22 carbon atoms in mammalian spermatozoa. Biochem J 240: 891–895.
Poulos A, Sharp P, Singh H, Johnson D, Fellenberg AJ, Pollard AC (1986b) Detection of a homologous series of C26-C38 polyenoic fatty acids in the brains of patients without peroxisomes (Zellweger’s syndrome). Biochem J 235: 607–610.
Poulos A, Singh H, Paton B, Sharp P, Derwas N (1986c) Accumulation and defective ß-oxidation of very long-chain fatty acids in Zellweger’s syndrome, adrenoleukodystrophy, and Refsum’s disease variants. Clin Genet 29: 397–408.
Robinson BS, Johnson DW, Poulos A (1990a) Metabolism of hexacosatetraenoic acid (C26:4, n-6) in immature rat brain. Biochem J 267: 561–564.
Robinson BS, Johnson DW, Poulos A (1990b) Unique molecular species of phosphatidylcholine containing very-long-chain (C24-C38) polyenoic fatty acids in rat brain. Biochem J 265: 763–767.
Sharp P, Johnson DW, Poulos A (1991) Molecular species of phosphatidylcholine containing very long chain fatty acids in human brain: Enrichment in X-linked adrenoleukodystrophy brain and diseases of peroxisomal biogenesis brain. J Neurochem 56: 30–37.
Sharp P, Pernios A, Fellenberg AJ, Johnson D (1987) Structure and distribution of polyenoic very long-chain fatty acids in the brain of peroxisome-deficient patients (Zellweger syndrome). Biochem J 248: 61–67.
Singh H, Usher S, Johnson DW, Poulos A (1990) A comparative study of straight chain and branched chain fatty acid oxidation in skin fibroblasts from patients with peroxisomal disorders. J Lipid Res 31: 217–225.
Street JM, Johnson DW, Singh H, Poulos A (1989) Metabolism of saturated and polyunsaturated fatty acids by normal and Zellweger syndrome skin fibroblasts. Biochem J 260: 647–655.
Wanders RJA, Heymans HSA, Schutgens RB, Barth PG, van den Bosch H, Tager JM (1988a) Peroxisomal disorders in neurology. J Neurol Sci 88: 1–39.
Wanders RJA, van Roermund CWT, van Wijland MJA, Schutgens RBH, Heikoop J, van den Bosch H, Schram AW, Tager JM (1987) Peroxisomal fatty acid ß-oxidation in relation to the accumulation of very long-chain fatty acids in cultured skin fibroblasts from patients with Zellweger syndrome and other peroxisomal disorders. J Clin Invest 80: 1778–1783.
Wanders RJA, van Roermund CWT, van Wijland MJA, Schutgens RBH, van den Bosch H, Schram AW, Tager JM (1988b) Direct demonstration that the deficient oxidation of very long-chain fatty acids in X-linked adrenoleukodystrophy is due to an impaired ability of peroxisomes to activate very long-chain fatty acids. Biochem Biophys Res Commun 153: 618–624.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1992 Springer Science+Business Media New York
About this chapter
Cite this chapter
Poulos, A. et al. (1992). Very Long-Chain Fatty Acids in Peroxisomal Disease. In: Bazan, N.G., Murphy, M.G., Toffano, G. (eds) Neurobiology of Essential Fatty Acids. Advances in Experimental Medicine and Biology, vol 318. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-3426-6_30
Download citation
DOI: https://doi.org/10.1007/978-1-4615-3426-6_30
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4613-6515-0
Online ISBN: 978-1-4615-3426-6
eBook Packages: Springer Book Archive