Localization of nervonic acid β-oxidation in human and rodent peroxisomes: impaired oxidation in Zellweger syndrome and X-linked adrenoleukodystrophy

Abstract

Studies with purified subcellular organelles from rat liver indicate that nervonic acid (C 24:1 ) is ␤ -oxidized preferentially in peroxisomes. Lack of effect by etomoxir, inhibitor of mitochondrial ␤ -oxidation, on ␤ -oxidation of lignoceric acid (C 24:0 ), a peroxisomal function, and that of nervonic acid (24:1) compared to the inhibition of palmitic acid (16:0) oxidation, a mitochondrial function, supports the conclusion that nervonic acid is oxidized in peroxisomes. Moreover, the oxidation of nervonic and lignoceric acids was deficient in fibroblasts from patients with defects in peroxisomal ␤ -oxidation [Zellweger syndrome (ZS) and X-linked adrenoleukodystrophy (X-ALD)]. Similar to lignoceric acid, the activation and ␤ -oxidation of nervonic acid was deficient in peroxisomes isolated from X-ALD fibroblasts. Transfection of X-ALD fibroblasts with human cDNA encoding for ALDP (X-ALD gene product) restored the oxidation of both nervonic and lignoceric acids, demonstrating that the same molecular defect may be responsible for the abnormality in the oxidation of nervonic as well as lignoceric acid. Moreover, immunoprecipitation of activities for acyl-CoA ligase for both lignoceric acid and nervonic acid indicate that saturated and monoenoic very long chain (VLC) fatty acids may be activated by the same enzyme. These results clearly demonstrate that similar to saturated VLC fatty acids (e.g., lignoceric acid), VLC monounsaturated fatty acids (e.g., nervonic acid) are oxidized preferentially in peroxisomes and that this activity is impaired in X-ALD. In view of the fact that the oxidation of unsaturated VLC fatty acids is defective in X-ALD patients, the efficacy of dietary monoene therapy, "Lorenzo's oil," in X-ALD needs to be evaluated.-Sandhir, R., M. Khan, A. Chahal, and I. Singh. Localization of nervonic acid ␤ -oxidation in human and rodent peroxisomes: impaired oxidation in Zellweger syndrome and X-linked adrenoleukodystrophy.

Plasma Lipolysis and Changes in Plasma and Cerebrospinal Fluid Signaling Lipids Reveal Abnormal Lipid Metabolism in Chronic Migraine

“…C24:1 is formed from C18:1 by three successive elongation reactions, and lower C24:1 levels are reported in demyelinating diseases ( Sargent et al, 1994 ). While the mitochondria oxidize most medium and long-chain fatty acids, peroxisomes are the oxidation site for VLC fatty acids ( Sandhir et al, 1998 ). C24:1 levels are regulated by biosynthesis/dietary uptake and by β-oxidation, and the higher C24:1 in CM suggests altered VLC fatty acid metabolism in plasma.…”

Prevention of Bortezomib-Induced Peripheral Neuropathy in Newly Multiple Myeloma Patients Using Nervonic Acid, Curcuma Rizoma, and L-Arginine Compound: A Pilot Study

“…2,3,5,25 The pathogenesis of neural damage underlying BINP is still limited, 42,45 however some studies report in animal models that the toxic effect is mainly directed toward satellite cell (Shwan cells, myelin) although axonal degeneration, oxidative stress and inflammation could also be present. 42,47,48 On this basis, we assumed that a nutraceutical compound composed of nervonic acid, curcumin and L-arginine, which are implicated in the biosynthesis of nerve cell myelin and exert an anti-inflammatory activity, [19][20][21][22][23][24][25] could preserve patients against BIPN. The neuroprotective effect that we expected did not occur.…”

“…It is also implicated as an intermediate in the biosynthesis of nerve cell myelin. 19 - 21 Curcumin has been demonstrated to have a variety of biologic activities, including anti-inflammatory activities and anticancer properties. 22 , 23 L-Arginine is an α-amino acid that is used in the biosynthesis of proteins.…”

“…17,18 There are new lines of evidence suggesting that other compounds, such as nervonic acid, curcumin, and L-arginine may play an important role against oxidative stress, favoring normal myelin function in neurodegenerative diseases as well as mitigating or preventing neuropathic and postoperative pain. [19][20][21][22][23][24][25] Nervonic acid is a monounsaturated fatty acid and exists in nature as an elongation product of oleic acid. It is also implicated as an intermediate in the biosynthesis of nerve cell myelin.…”

Bearing Habits of Acer truncatum and the Relationship Between Its Branch Characteristics and Fruiting Performance

“…Nervonic acid, 24:1 (n-9), is the most important fatty acid in the myelin sheath of nerve cells and plays an important role in maintaining the normal function of the brain and nervous system (Martínez and Mougan, 1998;Amminger et al, 2011;Kageyama et al, 2017;. A lack of nervonic acid is associated with demyelinating diseases such as multiple sclerosis and adrenoleukodystrophy (Sargent et al, 1994;Sandhir et al, 1998;. Oral supplementation of nervonic acid could be beneficial patients suffering from these diseases (Bettger et al, 2001;Lewkowicz et al, 2019).…”