Arginine biosynthesis pathway

L-argininosuccinate from citrulline and L-aspartate in the arginine biosynthesis pathway potential Cdc28p substrate... 

S. Moncada, R.MJ. Palmer, and E.A. Higgs, Biosynthesis of nitric-oxide from L-arginine — a pathway for the regulation of cell-function and communication. Biochem. Pharmacol. 38, 1709-1715 (1989). 

Farago, A. Denes, G. Mechanism of arginine biosynthesis in Chlamydomo-nas reinhardti. II. Purification and properties of N-acetylglutamate 5-phos-photransferase, the allosteric enzyme of the pathway. Biochim. Biophys. Acta, 136, 6-18 (1967)... 

By use of synthetic medium the formation of 3,4-trans-CH D was maintained for a 36-h cultivation period, resulting in accumulation of up to 790 mg L 1 3,4-trans-CHD 1 [11]. With this strain, however, it is necessary to separate the growth and production phases, because the substances for which E. coli strain BN117 is known to be auxotrophic, i.e. tryptophan, tyrosine, phenylalanine, proline, arginine, histidine, and p-aminobenzoate, also partially inhibit entry to the chorismate biosynthesis pathway (feedback inhibition of DAHP-synthase). 

Dihydroorotate dehydrogenase, the enzyme catalyzing the dehydrogenation of dihydroorotate to orotate (reaction 4 of the pathway Fig. 15-15), is located on the outer side of the inner mitochondrial membrane. This enzyme has FAD as a prosthetic group and in mammals electrons are passed to ubiquinone. The de novo pyrimidine pathway is thus compartmentalized dihydroorotate synthesized by trifunctional DHO synthetase in the cytosol must pass across the outer mitochondrial membrane to be oxidized to orotate, which in turn passes back to the cytosol to be a substrate for bifunctional UMP synthase. Mammalian cells contain two carbamoyl phosphate synthetases the glutamine-dependent enzyme (CPSase II) which is part of CAD, and an ammonia-dependent enzyme (CPSase /) which is found in the mitochondrial matrix, and which is used for urea and arginine biosynthesis. Under certain conditions (e.g., hyperammonemia), carbamoyl phosphate synthesized in the matrix by CPSase I may enter pyrimidine biosynthesis in the cytosol. 

Intensive study of mitomycin (18) biosynthesis 56 has not resolved all the problems of its origin. D-Glucosamine provides carbon and nitrogen for the aziridine ring and possibly a CgN unit joins with a C7N unit of less certain origin in the biosynthesis. The latter may be related to some intermediate of the shikimate pathway 57 and intermediates of the arginine biosynthetic pathway contribute the carbamoyl group 59,57, 60, 58t... 

Figure 22 Biosynthesis of polyamines through the arginine decarboxylase pathway. Putrescine derived from L-arginine through the action of three successive enzymes arginine decarboxylase (ADC), agmatine iminohydrolase (AIH), and N-carbamoylputrescine amidohydrolase (NCPAH).

Figure 30 The creatine (42) biosynthesis pathway consists of two enzymes L-arginine glycine amidinotransferase (AGAT) and guanidinoacetate A/-methyltransferase (GAMT). Atoms derived from glycine are shown in green, arginine in blue, and S-adenosylmethionine (AdoMet) in black.

Most pyrrolizidine alkaloids are esters of basic alcohols known as necine bases. The most frequently studied pyrrolizidine alkaloids are formed from the polyamines, putrescine and spermidine, and possess one of three common necine bases retronecine, heliotridine, and otonecine. Putrescine is utilized exclusively as a substrate in secondary metabolism, whereas spermidine is a universal cell-growth factor involved in many physiological processes in eukaryotes. Spermidine biosynthesis begins with the decarboxylation of SAM by SAM decarboxylase 165). The aminopropyl group is then transferred from decarboxylated SAM to putrescine by spermidine synthase to form spermidine (Scheme 5). Putrescine can be produced from ornithine by ODC. However, putrescine is derived from the arginine-agmatine pathway in pyrrolizidine alkaloid-producing plants due to the absence of ODC activity 166). 

Let us begin by examining arginine biosynthesis in Escherichia coli (Fig. 2). Natural selection puts a premium on the efficiency with which bacteria can utilize nutrients for growth and has thus led to the emergence of mechanisms for the feedback control of biosynthetic pathways. 

Recently a regulatory link has been established between the pathways of pyrimidine and arginine biosynthesis, each of which utilizes carbamoyl phosphate [89]. Orotate exercises an allosteric effect on ornithine transcar-bamylase and this effect is dependent upon both the carbamoyl phosphate and ornithine concentrations. When the carbamoyl phosphate level is high, orotate has the effect of changing the normally negative co operativity of ornithine transcarbamylase to a positive one, thus accelerating the conversion of carbamoyl phosphate in the arginine biosynthetic pathway. 

---