Research and Development of Liver Cytochrome p-450 Function Inspection Medicine by a ^<13>C-Breath Test

_L-[3^&13]丙氨酸，_L-[3-^&lt；13&>C]苯丙氨酸，_L-[3-^&lt；13&>C]酪氨酸，_L-[2-^&lt；13&>C]天冬氨酸，_L-[4-^&lt；13&>C]赖氨酸，_L-[4-^&lt；13&>C]谷氨酸，_L-[4-^&lt；13&g；C]谷氨酸；以溴乙酸苯酯和(S)-2-苯甘氨酚为手性甘氨酸代谢物，合成了谷氨酰胺、_L-[3-^&lt；13&gt；C]、_L-[5‘-^&lt；13&gt；C]和_L-[6’-^&lt；13&gt；C]。恶嗪酮与[^&lt；13&gt；C]烷基卤化物或[^&lt；13&gt；C]恶嗪酮与卤代烷的烷基化反应具有很高的非对映选择性。烷基化恶嗪酮的手性助剂的水解和去除得到了多种_L-[13&gt；C]氨基酸。肝病与血浆芳香族氨基酸苯丙氨酸和酪氨酸的异常升高有关。肝脏是芳香酸代谢的主要部位，特别是苯丙氨酸羟化为酪氨酸并进一步降解。我们研究了_L-苯丙氨酸呼气试验和_L-[1-^&t；13&gt；C]酪氨酸呼气试验对肝硬变患者肝损害的诊断价值。首先，比较了_L-[1-^&t；13&gt；C]苯丙氨酸和_L-[1-^&lt；13&gt；C]酪氨酸的排泄时间。峰值时间为20min。在两种呼气试验中，BUT_L-[1-^&lt；13&gt；C]酪氨酸呼气试验的峰值均高于_L-[1-^&lt；13&gt；C]苯丙氨酸呼气试验。将_L-苯丙氨酸呼气试验和_L-[1-^&t；13&gt；C]酪氨酸呼气试验参数与生化肝功能检测值进行比较。这些参数与传统上被认为是衡量肝细胞储备的几个肝脏血液测试值有很好的相关性。因此，_L-苯丙氨酸呼气试验和_L-[1-^&t；13&gt；C]酪氨酸呼气试验可用于评估肝功能障碍的程度和进展。

_L-[3^<-13>C]Alanine, _L-[3-^<13>C]phenylalanine, _L-[3-^<13>C]tyrosine, _L-[2-^<13>C]aspartic acid, and _L-[4-^<13>C]lysine, _L-[4-^<13>C]glutamic acid, _L-[4-^<13>C]glutamine, _L-[3-^<13>C]triptophan, _L-[5'-^<13>C] and _L-[6'-^<13>C]triptophan were synthesized using Dellaria's oxazinone, prepared from phenylbromoacetate and (S)-2-phenylglycinol, as achiral glycine equivalent. Alkylation of the oxazinone with [^<13>C]alkyl halide or the [^<13>C] oxazinone with alkyl halide was achieved with high diastereoselectivity. Hydrolysis and removal of chiral auxiliary of the alkylated oxazinone gave a variety of _L-[^<13>C]amino acid.Liver disease is associated with an abnormal elevation of the plasma concentrations of the aromatic amino acids phenylalanine and tyrosine. The liver is the main site of aromatic acid metabolism, particularly the hydroxylation of phenylalanine to tyrosine and further degradation. We have examined the usefulness of the _L-[1-^<13>C]phenylalanine breath test and _L-[1-^<13>C]tyrosine breath test for the detection of hepatic damage in patients with liver cirrhosis. First, the time course of ^<13>CO_2 excretion after the administration of _L-[1-^<13>C]phenylalanine and _L-[1-^<13>C]tyrosine were compared. The peak times were 20 min. in both breath test, but _L-[1-^<13>C]tyrosine breath test gave a higher peak than _L-[1-^<13>C]phenylalanine breath test. Next the parameter of _L-[1-^<13>C]phenylalanine breath test and _L-[1-^<13>C]tyrosine breath test were compared with biochemical liver function test values. These parameters were well correlated with several liver blood test values conventionally regarded as measures of hepatocyte reserve. Therefore, _L-[1-^<13>C]phenylalanine breath test and _L-[1-^<13>C]tyrosine breath test may be useful to assess the degree and progression of hepatic dysfunctions.