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口服抗吡哆醇化合物1-氨基-D-脯氨酸会进一步扰乱中度维生素B₆缺乏大鼠通过转硫途径的同型半胱氨酸代谢。

Oral exposure to the anti-pyridoxine compound 1-amino D-proline further perturbs homocysteine metabolism through the transsulfuration pathway in moderately vitamin B₆ deficient rats.

作者信息

Mayengbam Shyamchand, Raposo Sara, Aliani Michel, House James D

机构信息

Department of Human Nutritional Sciences, University of Manitoba, Winnipeg R3T2N2, Canada.

Department of Human Nutritional Sciences, University of Manitoba, Winnipeg R3T2N2, Canada; Department of Animal Science, University of Manitoba, Winnipeg R3T2N2, Canada.

出版信息

J Nutr Biochem. 2015 Mar;26(3):241-9. doi: 10.1016/j.jnutbio.2014.10.014. Epub 2014 Dec 3.

DOI:10.1016/j.jnutbio.2014.10.014
PMID:25524630
Abstract

Pyridoxal 5'-phosphate (PLP; a B₆ vitamer) serves as an important cofactor in a myriad of metabolic reactions, including the transsulfuration (TS) pathway, which converts homocysteine (Hcy) to cysteine. While overt vitamin B₆ deficiency is rare, moderate deficiency is common and may be exacerbated by anti-pyridoxine factors in the food supply. To this end, we developed a model of moderate B₆ deficiency and a study was conducted to examine the in vivo effect of 1-amino D-proline (1ADP), an anti-pyridoxine factor found in flaxseed, on indices of Hcy metabolism through the TS pathway in moderately B₆ deficient rats. Male weaning rats received a semi-purified diet containing either 7 mg/kg (control; CD) or 0.7 mg/kg (moderately deficient; MD) diet of pyridoxine·hydrochloride (PN∙HCl), each with 1 of 4 levels of 1ADP, viz. 0, 0.1, 1 and 10 mg/kg diet for 5 weeks. Perturbations in vitamin B₆ biomarkers were more pronounced in the MD group. Plasma PLP was significantly reduced, while plasma Hcy (8-fold) and cystathionine (11-fold) were increased in rats consuming the highest amount of 1ADP in the MD group. The activities of hepatic cystathionine β-synthase and cystathionine γ-lyase enzymes were significantly reduced in rats consuming the highest 1ADP compared to the lowest, for both levels of PN∙HCl. Dilation of hepatic central veins and sinusoids, mild steatosis and increased liver triglycerides were present in MD rats consuming the highest 1ADP level. The current data provide evidence that the consumption of an anti-pyridoxine factor linked to flaxseed may pose a risk for subjects who are moderate/severe vitamin B₆ deficient.

摘要

磷酸吡哆醛(PLP;一种维生素B₆形式)是众多代谢反应中的重要辅助因子,包括转硫途径(TS),该途径可将同型半胱氨酸(Hcy)转化为半胱氨酸。虽然明显的维生素B₆缺乏很少见,但中度缺乏很常见,并且食物供应中的抗吡哆醇因子可能会使其加剧。为此,我们建立了中度维生素B₆缺乏模型,并进行了一项研究,以检查亚麻籽中发现的抗吡哆醇因子1-氨基D-脯氨酸(1ADP)对中度维生素B₆缺乏大鼠通过TS途径的Hcy代谢指标的体内影响。雄性断奶大鼠接受含7 mg/kg(对照;CD)或0.7 mg/kg(中度缺乏;MD)盐酸吡哆醇(PN∙HCl)的半纯化饮食,每种饮食含有4种水平的1ADP中的1种,即0、0.1、1和10 mg/kg饮食,持续5周。MD组中维生素B₆生物标志物的扰动更为明显。在MD组中,摄入最高量1ADP的大鼠血浆PLP显著降低,而血浆Hcy(8倍)和胱硫醚(11倍)增加。对于两种水平的PN∙HCl,与最低量1ADP相比,摄入最高量1ADP的大鼠肝脏胱硫醚β-合酶和胱硫醚γ-裂解酶的活性显著降低。摄入最高量1ADP水平的MD大鼠出现肝中央静脉和肝血窦扩张、轻度脂肪变性和肝脏甘油三酯增加。目前的数据表明,食用与亚麻籽相关的抗吡哆醇因子可能对中度/重度维生素B₆缺乏的受试者构成风险。

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