INITIAL STAGES IN THE BIOSYNTHESIS OF PORPHYRINS .2. FORMATION OF DELTA-AMINOLAEVULIC ACID FROM GLYCINE AND SUCCINYL-COENZYME-A BY PARTICLES FROM CHICKEN ERYTHROCYTES
INITIAL STAGES IN THE BIOSYNTHESIS OF PORPHYRINS .2. FORMATION OF DELTA-AMINOLAEVULIC ACID FROM GLYCINE AND SUCCINYL-COENZYME-A BY PARTICLES FROM CHICKEN ERYTHROCYTES
复制标题
DOI：
10.1042/bj0700071
复制
发表时间：
1958-01-01
影响因子：
4.1
通讯作者：
NEUBERGER, A
中科院分区：
文献类型：
--
作者：
GIBSON, KD;LAVER, WG;NEUBERGER, A
从贫血鸡的红细胞中获得的冻干颗粒的制剂由琥珀酸辅酶A和甘氨酸合成[增量]氨基酮戊酸。这是正确的，无论琥珀酸辅酶A是由琥珀酸或[α]-氧代戊二酸通过化学合成还是酶促生成的，除非添加了二磷酸吡啶核苷酸。从这些证据和其他证据可以得出结论，Laver，W.G.，Neuberger，A和UdenFriend，S(1958)所描述的从全颗粒中的[α]-氧-戊二酸合成[三角洲]氨基戊二酸。生物化学。J.70，4，涉及通过[α]-氧代戊二酸脱氢酶的作用形成琥珀酰辅酶A。磷酸吡哆醛的加入使[Delta]-氨基酮戊酸的合成增加1.5~3倍。有证据表明，磷酸吡哆醛与该酶结合牢固。琥珀酰辅酶A和甘氨酸的缩合过程中似乎没有其他辅因子参与。对氯苯甲酸汞、氰化物、L青霉胺和L半胱氨酸对该反应有较强的抑制作用。D-青霉胺、D-半胱氨酸和谷胱甘肽有轻微抑制作用，碘乙酰胺、叠氮化钠、[α][α]‘’联吡啶和一氧化碳无抑制作用，8-羟基喹啉和乙二胺四乙酸酯有轻微激活作用。氰化物的抑制作用在吡哆醛磷酸盐过量十倍的情况下不变。冻干颗粒与甘氨酸、乙酰辅酶A和磷酸吡哆醛孵育形成氨基丙酮，当乙酰辅酶A被丙酰和戊二酰辅酶A取代时，生成氨基酮类物质。整个颗粒由丙酮酸和甘氨酸生成氨基丙酮。这些反应比[Delta]-氨基酚-Vulic酸的合成要慢。认为甘氨酸的[α]-碳在与琥珀酰辅酶A缩合之前，通过甘氨酸的氨基与酶结合的磷酸吡哆醛之间形成席夫S碱而被活化，并在此基础上解释了氰化物、青霉胺和半胱氨酸对[Delta]-氨基酮戊酸合成的抑制作用。
Preparations of freeze-dried particles obtained from erythrocytes of anemic chickens synthesize [delta]-aminolevulic acid from succinylcoenzyme A and glycine. This is true, whether succinyl-coenzyme A is chemically synthesized or generated enzymically from succinate or [alpha]-oxoglutarate, unless diphosphopyridine nucleotide is added. It is concluded from this and other evidence that the synthesis of [delta]aminole-vulic acid from [alpha]-oxoglutarate in whole particles, described by Laver, W.G., Neuberger, A and Udenfriend, S (1958). Biochem. J. 70,4, involves the formation of succinyl-coenzyme A by the action of [alpha]-oxoglutaric dehydrogenase. The addition of pyridoxal phosphate stimulates the synthesis of [delta]-aminolevulic acid 1.5 to 3-fold. Evidence was obtained that pyridoxal phosphate is firmly bound to the enzyme. No other cofactor appears to be involved in the condensation of succinyl-coenzyme A and glycine. p-Chloromercuribenzoate, cyanide, L-penicillamine and L-cysteine inhibit the reaction strongly. D-Penicillamine, D-cysteine and glutathione inhibit slightly; iodoacetamide, sodium azide, [alpha][alpha]'' dipyridyl and carbon monoxide have no effect, while 8-hydroxyquinoline and ethy-lenediamine-tetra-acetate activate slightly. Inhibition by cyanide is unchanged in the presence of a tenfold excess of pyridoxal phosphate. Freeze-dried particles form aminoacetone on incubation with glycine, acetyl-coenzyme A and pyridoxal phosphate, and substances reacting as aminoketones when acetyl-coenzyme A is replaced by propionyl- and glutaryl-coenzyme A. Whole particles form aminoacetone from pyruvate and glycine. These reactions are slower than the synthesis of [DELTA]-aminole-vulic acid. It is suggested that the [alpha]-carbon of glycine is activated, before condensing with succinyl-coenzyme A, by the formation of a Schiff''s base between the amino group of glycine and enzyme-bound pyridoxal phosphate. The inhibition of the synthesis of [delta]-aminolevulic acid by cyanide, penicillamine and cysteine is explained on this basis.