College of Pharmacy, Seoul National University, San 56-1 Shinrim-Dong, Kwanak-Ku, Seoul 151-742, Korea.
Food Funct. 2019 Feb 20;10(2):1225-1234. doi: 10.1039/c8fo01457d.
Betaine is a methyl donor utilized in regeneration of methionine from homocysteine in a metabolic reaction catalyzed by betaine-homocysteine methyltransferase (BHMT), an enzyme mostly localized in the liver. However, we recently showed that the metabolism of sulfur-containing amino acids in the kidney was also influenced by betaine, which is attributable to elevation of renal methionine availability resulting from an increase in its supply through blood. In this study we investigated the change in pulmonary sulfur-containing amino acid metabolism by betaine and its potential beneficial effect on paraquat (PQ)-induced lung injury. Male rats were provided with betaine for 2 weeks prior to an intratracheal instillation of PQ (0.3 mg/500 μl kg-1). Two weeks after PQ exposure, histopathological assessment revealed severe fibrotic lesions accompanied with elevation of 4-hydroxyproline in the lung, which were all prevented effectively by betaine supplementation. PQ-induced DNA fragmentation in lymphocytes, reduction of oxidant scavenging capacity, expression of heme oxygenase 1 and inducible nitric oxide synthase in the lung, and elevation of serum transforming growth factor beta 1 were also inhibited. PQ instillation increased cysteine, but depleted glutathione in the lung. Betaine supplementation before PQ exposure suppressed the cysteine accumulation and increased the glutathione synthesis. The polyamine synthesis, which requires decarboxylated S-adenosylmethionine as a substrate, was also increased significantly. The results suggest that betaine may enhance pulmonary antioxidant capacity by modulating the metabolism of sulfur-containing amino acids and related substances despite the lack of BHMT in the lung.
甜菜碱是一种甲基供体，在甜菜碱同型半胱氨酸甲基转移酶（BHMT）催化的代谢反应中，用于从同型半胱氨酸中再生蛋氨酸，BHMT 主要定位于肝脏。然而，我们最近表明，肾脏中含硫氨基酸的代谢也受到甜菜碱的影响，这归因于通过血液增加其供应，从而导致肾脏蛋氨酸可用性增加。在这项研究中，我们研究了甜菜碱对肺部含硫氨基酸代谢的变化及其对百草枯（PQ）诱导的肺损伤的潜在有益作用。雄性大鼠在气管内滴注 PQ（0.3mg/500μlkg-1）前用甜菜碱处理 2 周。PQ 暴露 2 周后，组织病理学评估显示严重的纤维化病变，伴有肺 4-羟脯氨酸水平升高，这些病变均被甜菜碱补充有效预防。PQ 诱导的淋巴细胞 DNA 片段化、抗氧化能力降低、肺血红素加氧酶 1 和诱导型一氧化氮合酶的表达以及血清转化生长因子β 1 的升高也被抑制。PQ 滴注增加了半胱氨酸，但消耗了肺中的谷胱甘肽。PQ 暴露前补充甜菜碱可抑制半胱氨酸积累并增加谷胱甘肽合成。多胺合成也显著增加，其需要脱羧 S-腺苷甲硫氨酸作为底物。研究结果表明，尽管肺中缺乏 BHMT，甜菜碱仍可通过调节含硫氨基酸及其相关物质的代谢来增强肺部抗氧化能力。
