An overview of phenylalanine and tyrosine kinetics in humans
An overview of phenylalanine and tyrosine kinetics in humans
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DOI：
10.1093/jn/137.6.1549s
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发表时间：
2007-06-01
影响因子：
4.2
通讯作者：
Matthews, Dwight E.
中科院分区：
文献类型：
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作者：
Matthews, Dwight E.
Moss 和 Schoenheimer 于 1940 年首次在大鼠中使用苯丙氨酸示踪剂，以确定苯丙氨酸被羟基化为酪氨酸，首次确定了该途径的首要地位。直到 20 世纪 70-80 年代，苯丙氨酸和酪氨酸动力学才在人体中进行测量。首次应用是确定高苯丙氨酸血症和苯丙酮尿症患者苯丙氨酸羟基化的阻断程度，但该方法扩展到正常受试者中苯丙氨酸羟基化的测定。与患有先天性代谢缺陷的患者相比，在相对正常的受试者中测量苯丙氨酸处理和酪氨酸产生率的用途已被证明更多。使用示踪剂确定苯丙氨酸和酪氨酸代谢率的关键是开发适当的示踪剂模型。大多数应用都使用相对简单的模型，忽略细胞内羟化率成分。由于肝脏是体内羟基化的主要部位，因此可以通过肝脏制造和分泌的快速周转血浆蛋白（例如 Apo-B）在同位素稳态时的示踪剂富集来评估羟基化位点的细胞内富集。尽管使用氘代苯丙氨酸示踪剂存在潜在问题，但合适的示踪剂是可用的，并且已被证明可用于人体苯丙氨酸和酪氨酸动力学的一般测量。
The initial use of a tracer of phenylalanine was by Moss and Schoenheimer in rats in 1940 to determine that phenylalanine was hydroxylated to tyrosine, defining for the first time the primacy of this pathway. Phenylalanine and tyrosine kinetics were not measured in humans until the 1970-80s. The first application was to determine the degree of blockage of phenylalanine hydroxylation in patients with hyperphenylalanemia and phenylketonuria, but this approach was expanded to determination of phenylalanine hydroxylation in normal subjects. Far more uses have been demonstrated for measuring rates of phenylalanine disposal and tyrosine production in relatively normal subjects than in patients with in-born errors of metabolism. Key to use of tracers to determine phenylalanine and tyrosine metabolic rates has been the development of appropriate tracer models. Most applications have used relatively simple models ignoring the intracellular hydroxylation rate component. Because the liver is the primary site of hydroxylation in the body, the intracellular enrichment at the site of hydroxylation can be assessed from the tracer enrichments at isotopic steady state in rapid-turnover plasma proteins, such as Apo-B, made and secreted by the liver. Although there are potential problems with use of deuterated tracers of phenylalanine, suitable tracers are available and have been demonstrated for general measurement of phenylalanine and tyrosine kinetics in humans.