Dual influence of aging and vitamin B6 deficiency on delta-6-desaturation of essential fatty acids in rat liver microsomes

Bordoni, Alessandra; Hrelia, Silvana; Lorenzini, Antonello; Bergami, R; Cabrini, Luciana; Biagi, Pierluigi; Tolomelli, B

doi:10.1016/s0952-3278(98)90163-6

Cited by 41 publications

(48 citation statements)

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“…In this regard, the changes of C20:3n-6 and C22:6n-3 weight percentages in the deficient medium were indicative of nutritionally relevant responses. This finding is consistent with studies of vitamin B-6 deficiency in rats (5,11,13,38). It also should be noted that the intracellular PLP concentration in our study was approximately four times higher in the 2,000 nM PL group than the 10 nM PL group.…”

Section: Discussionsupporting

confidence: 93%

“…These findings reflect the greater supply of PL for cellular uptake but also the buffering of intracellular PLP concentrations in response to large variation in extracellular exposure to vitamin B-6. The fatty acid patterns reported here were consistent with those of previous rat studies showing higher linoleic and ␣-linolenic acid and lower arachidonic acid, EPA, and DHA in various tissue lipids with severe vitamin B-6 deficiency (5,11,13,38) and with those from our recent study of marginal vitamin B-6 deficiency induced by dietary vitamin B-6 restriction in healthy men and women (45). One hypothesis for this particular fatty acid pattern is an impaired synthesis of n-3 and n-6 LCPUFA in vitamin B-6 deficiency.…”

Section: Discussionsupporting

confidence: 91%

“…The observed effects of dietary vitamin B-6 restriction in healthy humans on plasma fatty acid profiles are consistent with this hypothesis (45). The activity of the first and rate-limiting enzyme of LCPUFA synthesis, ⌬-6 desaturase activity, has been reported to be 20 -50% lower in vitamin B-6-deficient rats compared with their pair-fed, vitamin B-6-adequate controls (5,38). However, the relation of such in vitro enzyme activity and the actual in vivo metabolic flux was not examined by previous studies.…”

Section: Discussionsupporting

confidence: 68%

“…⌬-6 Desaturase is the first rate-limiting enzyme of n-3/n-6 LCPUFA synthesis (8). Vitamin B-6-deficient rats have been reported to have 40 -60% less ⌬-6 desaturase activity than pair-fed vitamin B-6-adequate controls (5,38). Whether such effects are associated with the gene expression of ⌬-6 desaturase or associated enzymes in LCPUFA synthesis has not been determined.…”

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confidence: 99%

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Vitamin B-6 restriction impairs fatty acid synthesis in cultured human hepatoma (HepG2) cells

Zhao

Ralat

Silva

et al. 2013

American Journal of Physiology-Endocrinology and Metabolism

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Vitamin B-6 deficiency has been reported to alter n-6 and n-3 fatty acid profiles in plasma and tissue lipids; however, the mechanisms underlying such metabolic changes remain unclear. The objective of this study was to determine the effects of vitamin B-6 restriction on fatty acid profiles and fatty acid synthesis in HepG2 cells. Cells were cultured for 6 wk in media with four different vitamin B-6 concentrations (10, 20, 50, and 2,000 nM added pyridoxal, representing deficient, marginal, adequate, and supraphysiological conditions) that induced a range of steady-state cellular concentrations of pyridoxal phosphate. Total cellular lipid content was greatest in the deficient (10 nM pyridoxal) medium. The percentage of arachidonic acid and the ratio of arachidonic acid to linoleic acid in the total lipid fraction were ∼15% lower in vitamin B-6-restricted cells, which suggests that vitamin B-6 restriction affects n-6 fatty acid interconversions. Metabolic flux studies indicated significantly lower fractional synthesis rate of oleic acid and arachidonic acid at 10, 20, and 50 nM pyridoxal, whereas that of eicosapentaenoic acid was lower in the cells cultured in 10 nM pyridoxal. Additionally, relative mRNA expressions of Δ5 and Δ6 desaturases were 40–50% lower in vitamin B-6-restricted cells. Overall, these findings suggest that vitamin B-6 restriction alters unsaturated fatty acid synthesis, particularly n-6 and n-3 polyunsaturated fatty acid synthesis. These results and observations of changes in human plasma fatty acid profiles caused by vitamin B-6 restriction suggest a mechanism by which vitamin B-6 inadequacy influences the cardiovascular risk.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 68%

mentioning

confidence: 99%

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Vitamin B-6 restriction impairs fatty acid synthesis in cultured human hepatoma (HepG2) cells

Zhao

Ralat

Silva

et al. 2013

American Journal of Physiology-Endocrinology and Metabolism

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“…Iron is present in each terminal protein of the ‰6-desaturase enzyme complex [7] catalysing the initial step of CoA derivatives of linoleic and ·-linolenic acids to the longer-chain fatty acids. ‰6-Desaturase activity is affected by many nutritional and nonnutritional factors [8]. Relatively little is known about the interactions between vitamin B 6 and fatty acid metabolism [8,9].…”

Section: Introductionmentioning

confidence: 99%

Polyunsaturated Fatty Acid Plasma Content in Groups of General Population with LowVitamin B<sub>6</sub> or Low Iron Serum Levels

Krajcovicová-Kudlácková

Klvanová

Dušinská

2004

Ann Nutr Metab

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Experimental and human studies describe the adverse effect of iron or vitamin B₆ deficiencies on polyunsaturated fatty acid metabolism. Iron is present in end proteins of the δ6-desaturase enzyme complex, and vitamin B₆ deficiency can affect the transmethylation reaction of proteins. Plasma polyunsaturated fatty acid content was estimated in apparently healthy subjects of the general population with no consumption of fish and low vitamin B₆ serum levels (<3 µg/l; n = 21) or with low iron serum levels (men: <12 µmol/l; women: <10 µmol/l; n = 16) and compared to a control group (n = 22) with normal vitamin B₆ and iron serum levels (in reference range). The activities of the δ6-desaturase enzyme complex were calculated as product/precursor (conversion indices). In groups of subjects with low vitamin B₆ and low iron levels, δ6-desaturase activity together with δ5-desaturase activity (conversion of α-linolenic/18:3,n–3/ into eicosapentaenoic acid/20:5,n–3/) as well as the conversion index of docosahexaenoic acid formation (22:6,n–3) from 22:5,n–3 (second δ6-desaturase activity) were significantly reduced. The inhibition effect on fatty acid synthesis was more pronounced in subjects with low iron levels than in those with low vitamin B₆ levels. The conversion indices correlated significantly positively with vitamin B₆ or iron levels.

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Diet and Nutrition, and their Influence on Alzheimer's Disease and other Neurodegenerative Diseases

Rainey‐Smith

Creegan

Fuller³

et al. 2019

Neurodegeneration and Alzheimer's Disease

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Dual influence of aging and vitamin B6 deficiency on delta-6-desaturation of essential fatty acids in rat liver microsomes

Cited by 41 publications

References 11 publications

Vitamin B-6 restriction impairs fatty acid synthesis in cultured human hepatoma (HepG2) cells

Vitamin B-6 restriction impairs fatty acid synthesis in cultured human hepatoma (HepG2) cells

Polyunsaturated Fatty Acid Plasma Content in Groups of General Population with LowVitamin B<sub>6</sub> or Low Iron Serum Levels

Diet and Nutrition, and their Influence on Alzheimer's Disease and other Neurodegenerative Diseases

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