Patients with lysine‐related inborn errors of metabolism (pyridoxine‐dependent epilepsy [PDE] and glutaric aciduria type 1 [GA1]), follow a lysine‐restricted diet with arginine‐fortified lysine‐free amino acid formula and additional oral arginine supplementation as a newer therapy for PDE. The rationale of arginine supplementation is based on arginine's ability to compete with lysine transport across cell membranes via shared transporter systems. Adequate doses of arginine required to competitively inhibit enteral lysine uptake has not been studied in humans This proof‐of‐concept study investigates the effect of incremental enteral arginine doses on whole‐body lysine oxidation using an in vivo stable isotope tracer, L‐[1‐¹³C] lysine, in healthy humans. Five healthy men completed six study days each consuming one dose of l‐arginine HCl per study day; range = 50‐600 mg/kg/d. Lysine intake was at DRI (30 mg/kg/d). Breath samples were analysed for L‐[1‐¹³C] lysine oxidation to ¹³CO₂ using an isotope ratio mass spectrometer. Plasma amino acid concentrations were analysed using an amino acid analyser. Increasing doses of l‐arginine HCl caused a linear decrease in whole‐body lysine oxidation. Plasma arginine concentration increased, and plasma lysine concentration decreased below normal range with high arginine intakes. We provide the first empirical evidence of arginine‐lysine antagonism in response to increasing oral arginine doses. Results suggest 300‐600 mg/kg/d of l‐arginine HCl and lysine intake restricted to DRI is needed to reduce enteral lysine uptake and systemic lysine oxidation. This could potentially lead to a recommended dose for arginine in lysine‐related inborn errors of metabolism.

中文翻译：

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肠内精氨酸补充剂对人类赖氨酸代谢的影响：赖氨酸相关先天性代谢错误的概念验证。

患有赖氨酸相关先天性代谢障碍（吡哆醇依赖性癫痫 [PDE] 和 1 型戊二酸尿症 [GA1]）的患者，遵循赖氨酸限制饮食和精氨酸强化的无赖氨酸氨基酸配方和额外的口服精氨酸补充剂PDE 的新疗法。补充精氨酸的基本原理是基于精氨酸通过共享转运系统与赖氨酸跨细胞膜转运竞争的能力。尚未在人体中研究竞争性抑制肠内赖氨酸摄取所需的足量精氨酸 该概念验证研究使用体内稳定同位素示踪剂 L-[1] 研究了增加肠内精氨酸剂量对全身赖氨酸氧化的影响- ¹³C] 赖氨酸，在健康人体内。五名健康​​男性完成了六个研究日，每个研究日每人服用一剂l-精氨酸 HCl；范围 = 50-600 mg/kg/d。赖氨酸摄入量为 DRI (30 mg/kg/d)。使用同位素比质谱仪分析呼气样品的 L-[1- ¹³ C] 赖氨酸氧化为¹³ CO ₂。使用氨基酸分析仪分析血浆氨基酸浓度。增加剂量的l‐精氨酸 HCl 导致全身赖氨酸氧化呈线性下降。血浆精氨酸浓度增加，血浆赖氨酸浓度降低至精氨酸摄入量高的正常范围以下。我们提供了精氨酸-赖氨酸拮抗作用对增加口服精氨酸剂量的反应的第一个经验证据。结果表明，需要 300-600 mg/kg/d 的l-精氨酸 HCl 和赖氨酸摄入量限制在 DRI 中，以减少肠内赖氨酸摄取和全身赖氨酸氧化。这可能会导致在赖氨酸相关的先天性代谢错误中推荐使用精氨酸剂量。