Uncertainties remain in the catabolism of valine
Uncertainties remain in the catabolism of valine
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缬氨酸的分解代谢仍存在不确定性
DOI：
10.1016/0968-0004(86)90147-7
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发表时间：
1986
影响因子：
13.8
通讯作者：
H. Akers
中科院分区：
文献类型：
--
作者：
D. Wolf;H. Akers
已知缬氨酸的oxMalive降解通过甲基丙二酸酯系列/-非酶促脱羧反应进行，生成醛中间体sucdnyl-CoA。良好的证据表明，至少一种C3间丙醛在生理介导下参与甲基丙二酸半醛向琥珀酰-CoA的转化条件。人类也使用一个C一个中间然而，细节&是转换，至少在高等生物体中，仍然不清楚，介导的降解途径的缬氨酸。一名患有遗传缺陷的患者，虽然完整的分解代谢途径是丙醛的氧化，但MM-CoA位点（大多数氨基酸的甲基化是通过丙酸，丙酰-CoA，丙二酸血症）在几十年前被给予13 C-，问题和MM-CoA;以及直接氧化标记的缬氨酸。关于MMS到MM-CoA的缬氨酸的末端步骤的核磁共振以及随后的降解产物的核磁共振（NMR）光谱仍然未得到解决。缬氨酸羧化成丙酰辅酶A（图1）。尿代谢物的研究表明，在第一次努力阐明存在，但不是身份，一个C3微生物和高等动物，但很少分解代谢的命运，缬氨酸是针对中间体之前，MM-CoA的研究已经与植物，确定潜在的第9阶段，一个发现后来扩展到nor-Valine代谢物也是重要的，这种氨基酸。Rose和同事3只雄性大鼠10只。因此，证据支持，因为他们贡献他们的碳证明在1942年，在狗至少有一个C中间缬氨酸骨架的物质，如根皮苷诱导的糖尿，一半cataline。saicin I，辛辣成分辣椒-腹腔注射缬氨酸周围的不确定性的pers，或维生素泛酸2.其中，α-酮异戊酸被转化为将MMS转化为α的方法，对于初始事件普遍一致，没有伴随C的尿糖，1968年澄清了缬氨酸分解代谢的中间体，其中包括酮尿的反式增加。由于通过鉴定丙二酸甲酯胺化，随后氧化，缬氨酸半醛脱氢酶H在假羧化产生异丁酰辅酶A中的这些性质与异丁酸酯的性质（一种铜绿假单胞菌）不相似。该酶催化随后的13-氧化和硫酯易形成的中间体，在催化MMS直接转化为水解前体的过程中产生S-甲基丙二酸缬氨酸，他们认为α-丙酰-CoA与半醛（MMS）同时还原。随后的酮异戊酸由NAD的脱氨形成。以上证据表明，MMS转化为R-甲基化的缬氨酸被脱羧产生，表明缬氨酸丙二酰辅酶A（MM-CoA）在葡萄糖形成之前代表异丁酸，从1-羟基异丁酸转移到该途径的未解析区段。Atchley 4确定丙酸为MMS，然后为丙酰辅酶A（其中一种可能的途径涉及异丁酸酯代谢的脱碳中间体损失缬氨酸的原始碳-2）。在兔肾匀浆中氧化MMS以产生丙酰-CoA，这是一种系统。丙酰-CoA可能会被进一步代谢以产生不能进一步氧化丙酸的物质，被羧化以产生MM-CoA，即琥珀酰-CoA。Atchley提出的一个明显的困境是，~-氧化路线将经历重排，以在这条路线中的前存在，因为甲基为…
The oxMalive degradation of valine is known to proceed through a methylmalonate sere/-a non-enzymatic decarboxylation to aldehyde intermediate to sucdnyl-CoA. Good evidence suggests that at least one C 3 inter- propionaldehyde under physiological mediate i~ involved in the conversion of methylmalonate semialdehyde to succinyl-CoA, conditions. Humans also use a C a inter-However, the details of&is conversion, at least in higher organisms, remain unclear, mediate in the degradation pathway of valine. A patient with a genetic defect at While the complete catabolic pathways sequent oxidation of propionaldehyde the MM-CoA mutase locus (methylfor most of the amino acids were eluci-through propionate, propionyl-CoA, malonicacidemia) was administered 13C-dated several decades ago, questions and MM-CoA; and the direct oxidation labeled valine. Nuclear magnetic resonconcerning the terminal steps of valine of MMS to MM-CoA followed by de-ance (NMR) spectroscopy of the resultdegradation remain unresolved. Valine carboxylationtopropionyl-CoA (Fig. 1). ing urinary metabolites indicated the catabolism has been investigated in The first efforts toward elucidating the existence, but not the identity of, a C 3 microbes and higher animals, but few catabolic fate of valine were directed at intermediate prior to the MM-CoA studies have been made with plants, determining the gluconeogenic potential stage 9, a finding later extended to nor-Valine metabolites are also important of this amino acid. Rose and colleagues 3 mal rats 10. Thus, the evidence supports because they contribute their carbon demonstrated in 1942 that in dogs with at least one C a intermediate in valine skeletons to substances such as cap-phlorhizin-induced glycosuria, one half catabolism. saicin I, the pungent component in pep-of the intraperitoneally injected valine The uncertainty surrounding the pers, or the vitamin pantothenate 2. There or ct-ketoisovalerate was converted to method of the conversion of MMS to a is general agreement on the initial events urinary glucose with no concomitant C a intermediate was clarified in 1968 of valine catabolism which include trans-increase in ketonuria. Because of the by the identification of methylmalonate amination followed by oxidative de-similarities of these properties of valine semialdehyde dehydrogenase H in Pseudo-carboxylation to yield isobutyryI-CoA, to the properties of isobutyrate, a plaus- monas aeruginosa. This enzyme catalyses Subsequent 13-oxidation and thioester ible intermediate in the catabolism of the direct conversion of MMS to prohydrolysis produces S-methylmalonate valine, they suggested that the ct-pionyl-CoA with the concurrent reduction semi-aldehyde (MMS). The ensuing ketoisovalerate formed from deamin-of NAD. The above lines of evidence conversion of MMS to R-methyl-ation of valine is decarboxylated to yield suggest that the catabolism ofvaline promalonyl-CoA (MM-CoA) represents isobutyrate prior to glucose formation, ceeds from~ l-hydroxyisobutyric acid to the unresolved segment of the pathway. Atchley 4 identified propionate as an MMS, then to propionyl-CoA (with the One possible route involves the decarb-intermediate of isobutyrate metabolism loss of the original carbon-2 of valine). oxylation of MMS to give propionyl-CoA in a rabbit kidney homogenate, a system The propionyl-CoA would presumably which is further metabolized to produce that cannot further oxidize propionate, be carboxylated to yield MM-CoA which succinyl-CoA. An apparent dilemma Atchley proposed a~-oxidation route would undergo a rearrangement to proexists in this route because the methyl-for the …