Argininosuccinate lyase

Turner MA et al Human argininosuccinate lyase a structural basis for intragenic complementation. Proc Natl Acad Sci U S A 1997 94 9063. 

Argininosuccinate lyase (AL) (Fig. 40-5 reaction 4) cleaves argininosuccinate to form fumarate, which is oxidized in the tricarboxylic acid cycle, and arginine, which is hydrolyzed to urea and ornithine via hepatic arginase. Both AL and arginase are induced by starvation, dibutyryl cyclic-AMP and corticosteroids. 

R. Debuchy, S. Purton, J.-D. Rochaix (1989) The argininosuccinate lyase gene of Chlamydomonas reinhardtii. An important tool for nuclear transformation and for correlating the genetic and molecular maps of the arg7 locus. EMBOJ., 8 2803-2809... 

Condition Carbamoyl- phosphate synthetase Ornithine transcarbamoylase Argininosuccinate synthetase Argininosuccinate lyase Arginase... 

In view of the toxicity of ammonia, complete absence of any one of the enzymes of the cycle is fatal. Nonetheless, disorders of the cycle do occur, which are caused by a low activity of one of the enzymes or carbamoyl phosphate synthetase. In addition, defects in N-acetylglutamate synthase have been reported, but they are very rare. With the exception of ornithine transcarbamoylase, the deficiencies have an autosomal recessive mode of inheritance. The transcarbamoylase deficiency is inherited as an X-linked dominant trait, usually lethal in male patients. A deficiency of carbamoyl phosphate synthetase, ornithine transcarbamoylase or argininosuccinate synthetase results in accumulation and excretion of citrulline. A deficiency of argininosuccinate lyase results in the accumulation and excretion of argininosuccinate and arginine (Table 10.5). The abbreviations CPSD, OTCD, ASD, ALD and AD stand, respectively, for the deficiencies of these enzymes, where D stands for deficiency. 

Fumarate NADH Formation Fumarase, Malate Dehydrogenase Argininosuccinate Lyase ... 

OCTOPINE DEHYDROGENASE ARGININOSUCCINATE LYASE ARGININOSUCCINATE SYNTHETASE ARISTOLOCHENE SYNTHASE Arogenate dehydrogenase,... 

Other enzymes that catalyze elimination reactions that produce fumarate are aspartate ammonia-lyase (aspartase),63 argininosuccinate lyase (Fig. 24-10, reaction g),64/65 and adenylosuccinate lyase... 

Arginine Proline Proline oxidase Ornithine-glutamate transaminase Ornithine transcarbamoylase Argininosuccinate synthase Argininosuccinate lyase... 

The complete urea cycle as it occurs in the mammalian liver requires five enzymes Argininosuccinate synthase, arginase, and argininosuccinate lyase (which function in the cytosol), and ornithine transcarbamoylase, and carbamoyl phosphate synthase (which function in the mitochondria). Additional specific transport proteins are required for the mitochondrial uptake of L-ornithine, NH3, and HC03 and for the release of L-citrulline. 

Fumarate is a product of both argininosuccinate lyase (fig. 22.7) and fumarylacetoacetase (fig. 22.12), even though the reactions are quite different. If you were describing these two reactions to an organic chemistry student using one word per reaction, what words would you pick ... 

Quantitation of plasma amino acids, especially of citrullinc, is the first step in determining the precise enzyme or transport protein defect in patients with a UCD. If the defect involves N-acetyglutamate synthetase (NAGS), CPSI, or OTC, then plasma citrulline concentration will be low. Marked hypercitrullinemia (>2000 pmol/I.) is seen in argininosuccinate synthetase (AS) deficiency, while moderate increases (>200 pmol/L, normal undetectable) are found in argininosuccinate lyase (AL) and citrin deficiencies. In AL deficiency, the presence of argininosuccinic acid and its anhydrides further distinguishes this disorder. 

The most important part of the search for sequence relationships is the completeness of the database. Early in the discovery that taxon-specific crystallins were related to enzymes, no relatives of relationship between yeast argininosuccinate lyase (ASL) and chicken lens -crystallins was seen. In fact, the yeast ASL sequence was published on the same day as a personal database the sequence of human ASL, which was just being published.28 There is no substitute for complete and up-to-date databases. 

Argininosuccinate lyase (the third enzyme) reversibly catalyzes the cleavage of argininosuccinate to arginine and fumarate. 

The main reason is probably that the system evolved to keep the fumarate concentration low, because fumarate (and arginine) readily inhibits argininosuccinate lyase. Thus, this enzyme is cytoplasmic it is not inhibited by the high concentration of fumarate from the citric acid cycle since this fumarate is in the mitochondrion. 

M.A. Turner, A. Simpson, R.R. Mclnnes, and P.L. Howell. 1997. Human argininosuccinate lyase A structural basis for... 

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