College of Agricultural and Environmental Sciences, University of California, Davis, CA, 95616, USA.
Department of Food & Nutritional Sciences, University of Reading, Reading, RG56 6DX, UK.
Mol Nutr Food Res. 2023 Sep;67(17):e2300281. doi: 10.1002/mnfr.202300281. Epub 2023 Jul 9.
Dietary flavan-3-ols are known to mediate cardiovascular benefits. Currently, it is assumed that the levels of flavan-3-ol catabolites detected in humans, 5-(3',4'-dihydroxyphenyl)-γ-valerolactone (γVL) and 5-(3',4'-dihydroxyphenyl)-γ-valeric acid (γVA), and their corresponding phase II metabolites, are determined exclusively by the action of the gut microbiome. However, a family of human proteins, paraoxonase (PON), can theoretically hydrolyze γVL metabolites into the corresponding γVAs. This study aims to determine if PON is involved in γVL and γVA metabolism in humans.
A rapid conversion of γVL into γVA is detected in serum ex vivo (half-life = 9.8 ± 0.3 min) that is catalyzed by PON1 and PON3 isoforms. Phase II metabolites of γVL are also reacted with PON in serum. Following an intake of flavan-3-ol in healthy males (n = 13), the profile of γVA metabolites detected is consistent with that predicted from the reactivity of γVL metabolites with PON in serum. Furthermore, common PON polymorphisms are evaluated to assess the use of γVL metabolites as biomarkers of flavan-3-ol intake.
PONs are involved in flavan-3-ol metabolic pathway in humans. PON polymorphisms have a minor contribution to inter-individual differences in the levels of γVL metabolites, without affecting their use as a nutritional biomarker.
膳食黄烷-3-醇已知具有调节心血管益处的作用。目前，人们认为在人体中检测到的黄烷-3-醇代谢物水平，即 5-(3',4'-二羟基苯基)-γ-缬草酸（γVL）和 5-(3',4'-二羟基苯基）-γ-戊酸（γVA），及其相应的 II 相代谢物，仅由肠道微生物组的作用决定。然而，人类蛋白家族对氧磷酶（PON）理论上可以将 γVL 代谢物水解为相应的 γVAs。本研究旨在确定 PON 是否参与人体中 γVL 和 γVA 的代谢。
在血清外体中检测到 γVL 快速转化为 γVA（半衰期=9.8±0.3 分钟），这一过程由 PON1 和 PON3 同工酶催化。γVL 的 II 相代谢物也与血清中的 PON 发生反应。在健康男性（n=13）摄入黄烷-3-醇后，检测到的 γVA 代谢物谱与 γVL 代谢物与血清中 PON 反应所预测的谱一致。此外，还评估了常见的 PON 多态性，以评估 γVL 代谢物作为黄烷-3-醇摄入的生物标志物的使用。
PON 参与了人类黄烷-3-醇代谢途径。PON 多态性对 γVL 代谢物水平的个体间差异只有很小的影响，而不影响其作为营养生物标志物的使用。
