Decarboxylated S- adenosylmethionine

The assay was carried out in phosphate buffer with radioactive putrescine, decarboxylated S-adenosylmethionine, and enzyme. Reactions were incubated at 37°C for 90 minutes and terminated by addition of perchloric acid. The solutions were clarified by centrifugation, and the polyamines were benzoyl-ated and extracted and then analyzed. Figure 9.55 shows the analysis of samples removed at zero time (blank) and in after 60 minutes incubation (sample) at 37°C. The appearance of radioactive spermidine is shown. The rate of product formation is shown in Figure 9.56. 

Dufe, V. T., Qiu, W., Muller, I. B., Hui, R., Walter, R. D., and Al-Karadaghi, S. (2007). Crystal structure of Plasmodium falciparum spermidine synthase in complex with the substrate decarboxylated S-adenosylmethionine and the potent inhibitors 4MCHA and Ado-DATO. ]. Mol. Biol. 373,167-177. 

Polyamine metabolism by parasites differs in several significant ways from the mammalian host these include, but are not limited to, enzyme half-life, turnover, substrate specificity, types and quantities of polyamines produced. The production of the novel bis glutathionyl spermidine adduct by trypanosomatids, its role as an antioxidant and the protein structure of trypanothione reductase is discussed with respect to the more conventional glutathione reductase system. The role of S-adenosylmethionine and decarboxylated S-adenosylmethionine as critical precursors in the biosynthesis of the higher polyamines is explored with respect to differences in the function and control of the pathway by various parasites. Polyamine biosynthesis in parasites is sufficiently different from that of the host to afford multiple opportunities for drug development, these may be aimed directly at circumventing polyamine biosynthesis or at inhibiting precursors necessary for polyamine synthesis. 

Phosphatidylcholine can be synthesized by the pathway shown in Figure 14.3. Decarboxylation of phosphatidylserine to phosphatidylethanolamine (cephalin) is followed by methylation in which S-adenosylmethionine is the methyl donor to yield successively the relatively rare mono- and dimethyl derivatives, then phosphatidylcholine. 

Methionine is converted into succinyl CoA in nine steps (Figure 23.2.7). The first step is the adenylation of methionine to form methyl donor in the cell (Section 24.2.7). Methyl donation and deadenylation yield homocysteine, which is eventually processed to a-ketobutyrate. The enzyme a-ketoacid dehydrogenase complex oxidatively decarboxylates a-ketobutyrate to propionyl CoA, which is processed to succinyl CoA as described in Section 23.3.3. 

In bacteria, the decarboxylation of phosphatidyl serine by a pyridoxal phosphate-dependent enzyme yields phosphatidyl ethanolamine, another common phospholipid. The amino group of this phosphoglyceride is then methylated three times to form phosphatidyl choline. S-Adenosylmethionine is the methyl donor. 

In bacteria, decarboxylation of this phosphoglyceride yields phosphatidyl ethanolamine, which is methylated by S-adenosylmethionine to form phosphatidyl choline. In mammals, this phosphoglyceride is synthesized by a pathway that utilizes dietary choline. CDP-choline is the activated intermediate in this route. 

The type II pneumocytes synthesize phosphatidylcholine in a fashion quite different from that in other cells. Most other cells synthesize phosphatidylserine from cytidine diphosphate diacylglycerol and serine. The phosphatidylserine is then decarboxylated to yield phosphatidyl ethanoiamine. The final step is the successive donation of three methyl groups via S-adenosylmethionine to form phosphatidylcholine. The pulmonary biosynthetic pathway is shown in Figure 54-2. The enzyme choline phosphotransferase forms PC directly from cytidine diphosphocholine and diacylglycerol. Phosphatidylinositol formation peaks at about 35 weeks. As PI decreases in concentration, PG begins to increase. 

Synthesis of uroporphyrinogen III from 6-ALA via porphobilinogen. - 2) C-Methylation of uroporphyrinogen III by a series of different methyltransferases with use of S-adenosylmethionine (SAM), decarboxylation, ring contraction, and incorporation of cobalt with formation of cobyrinic acid, the simplest representative of the naturally occurring corrins. - 3) Conversion of cobyrinic acid to cobalamin and then to the coenzyme form of V. B 2. 

The pyrrolidine moiety in nicotine originates from ornithine, which is first decarboxylated in apyridoxal phosphate-mediated step. After methylation with S-adenosylmethionine (SAME) and ring-closure, cleavage of pyridoxamine phosphate yields the 1-methyl-3,4-dihydropyrrolium salt. 

Like the thyroid hormone thyroxine, noradrenaline and adrenaline originate as well from the amino acid tyrosine, which is formed in the liver by hydroxylation of phenylalanine. Tyrosine is hydroxylated a second time in the aromatic ring and, subsequent to decarboxylation, again in the side-chain. The JV-methylation of noradrenaline with S-adenosylmethionine in the chromaffin cells of the adrenal medulla leads finally to adrenaline. [107]... 

Among these polyamines, putrescine is biosynthesized from ornithine by decarboxylation with ornithine decarboxylase. Putrescine receives a propyl-amino rmit (C3N unit) from decarboxylated SAM (S-adenosylmethionine) to form spermidine. SAM is derived from methionine. Spermidine synthase catalyzes this biosynthetic process. Spermine is formed from spermidine through the addition of a C3N unit from a decarboxylated SAM unit under the catalysis of spermine synthase [3]. 

A. Schenone, Specific inhibition of the enzyme decarboxylation of S-adenosylmethionine by methylglyoxal bis (guanilhydrazone) and related substances, Biochem. J., 139 351 (1974). 

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