Adenosine triphosphate synthetase

Fig. 8.10. The organisation of the mitochondrial genome from the domestic fowl (Desjardins Morals, 1990). The genes for the tRNAs for each amino acid are indicated by the single amino acid code. Genes for proteins are indicated thus Cyt b, cytochrome b ND, NADH dehydrogenase CO, cytochrome oxidase ATPase, adenosine triphosphate synthetase. In each, the subunit number is given as the suffix. The two concentric circles represent the L- (light) and H- (heavy) strands.

Such enzymes catalyse the condensation of specific compounds, accompanied by the breakdown of a pyrophosphate bond in adenosine triphosphate (10.64). Adenosine is the condensation product of a pentose (D-ribofuranose) and a purine (adenine). Scheme 10.15 shows the action of glutamine synthetase on a mixture of L-glutamic acid (10.65) and... 

Phosphoribosylpyrophosphate (PRPP) synthetase is one of the very few enzymes which transfer a pyrophosphoryl group from ATP in one step. When the synthesis is carried out in lsO-enriched water, lsO is incorporated into the PRPP, but not into AMP.91 The lsO in the PRPP arises from a pre-exchange between the H2180 and the ribose phosphate, and hence the results confirm that fission of the /5-P—O bond takes place. PRPP and ATP are starting materials in the biosynthesis of histidine, and Ai-(5 -phospho-D-ribosyl)adenosine triphosphate (29) is an intermediate. The... 

For most amino acids, the ester linkage between the ct-COOH group of the amino acid and the 3 -terminal adenosine of a cognate tRNA is formed in a two-step mechanism catalyzed by an aminoacyl-tRNA synthetase (aaRS). ° In this so-called direct pathway, the aaRS first catalyzes the reaction of the amino acid with adenosine triphosphate (ATP), yielding the enzyme-bound high-energy intermediate aa AMP and PPi in the second step, this aaRS-bound intermediate reacts with tRNA to yield aa-tRNA and AMP (Figure 1). 

The first step of this sequence, which is not unique to de novo purine nucleotide biosynthesis, is the synthesis of 5-phosphoribosylpyrophosphate (PRPP) from ribose-5-phosphate and adenosine triphosphate. Phosphoribosyl-pyrophosphate synthetase, the enzyme that catalyses this reaction [278], is under feedback control by adenosine triphosphate [279]. Cordycepin interferes with thede novo pathway [229, 280, 281), and cordycepin triphosphate inhibits the synthesis of PRPP in extracts from Ehrlich ascites tumour cells [282]. Formycin [283], probably as the triphosphate, 9-0-D-xylofuranosyladenine [157] triphosphate, and decoyinine (LXXlll) [284-286] (p. 89) also inhibit the synthesis of PRPP in tumour cells, and this is held to be the blockade most important to their cytotoxic action. It has been suggested but not established that tubercidin (triphosphate) may also be an inhibitor of this reaction [193]. 

Some of the reactions of PO3- parallel enzymatic reactions promoted by adenosine triphosphate (ATP). Pyruvate kinase catalyzes the equilibration of ATP and pyruvate with adenosine diphosphate (ADP) and phosphoenol pyruvate (11,12). In a formal sense, this reaction resembles the preparations of enol phosphate (eqs. 6 and 7). Cytidine triphosphate synthetase catalyzes the reaction of uridine triphosphate with ammonia to yield cytidine triphosphate (13). In a formal sense, this reaction resembles the replacement of the ester carbonyl group of ethyl acetate by the nitrogen of aniline (eq. 8). 

Jhe synthesis of proteins, as characterized by the in vitro incorporation of amino acids into the protein component of cytoplasmic ribonu-cleoprotein, is known to require the nonparticulate portion of the cytoplasm, ATP (adenosine triphosphate) and GTP (guanosine triphosphate) (15, 23). The initial reactions involve the carboxyl activation of amino acids in the presence of amino acid-activating enzymes (aminoacyl sRNA synthetases) and ATP, to form enzyme-bound aminoacyl adenylates and the enzymatic transfer of the aminoacyl moiety from aminoacyl adenylates to soluble ribonucleic acid (sRNA) which results in the formation of specific RNA-amino acid complexes—see, for example, reviews by Hoagland (12) and Berg (1). The subsequent steps in pro-... 

Animal and bacterial enzymes that utilize or synthesize carbamyl phosphate have activity with acetyl phosphate. Acyl phosphatase hydrolyzes both substrates, and maybe involved in the specific dynamic action of proteins. Ornithine and aspartic transcarbamylases also synthesize acetylornithine and acetyl aspartate. Finally, bacterial carbamate kinase and animal carbamyl phosphate synthetase utilize acetyl phosphate as well as carbamyl phosphate in the synthesis of adenosine triphosphate. The synthesis of acetyl phosphate and of formyl phosphate by carbamyl phosphate synthetases is described. The mechanism of carbon dioxide activation by animal carbamyl phosphate synthetase is reviewed on the basis of the findings concerning acetate and formate activation. 

Eugene Kennedy and Albert Lehninger showed in 1949 that fatty acids are oxidized in mitochondria. Subsequent work demonstrated that they are activated before they enter the mitochondrial matrix. Adenosine triphosphate (ATP) drives the formation of a thioester linkage between the carboxyl group of a fatty acid and the sulfhydryl group of CoA. This activation reaction takes place on the outer mitochondrial membrane, where it is catalyzed by acyl CoA synthetase (also called fatty acid thiokinase). 

Figure 24-2 The urea cycle pathway. CPS I, Carbamyl phosphate synthetase I N-acetyigiutamate as positive allosteric effector OTC, ornithine transcarbamyiase MS, argininosuccinate synthetase Ai, argininosuccinate iyase AR, arginase ADP, adenosine diphosphate, ATf adenosine triphosphate, P, inorganic phosphate.

Synthetase, adenosine triphosphate 429b, 922d, 3844b, 4249... 

In 1990, La wen and Zocher (49) described the purification and characterization of the enzyme cyclosporin synthetase, isolated from the mycelium of the strain T. inflatum NRRL 8044 (S 7939/45). This enzyme synthesizes cyclosporin A by a thiotemplate mechanism starting from the precursor amino acids in their unmethylated form, utilizing adenosine triphosphate ATP)/Mg, and with S-adenosyl-L-methionine as methyl donor. The first attempts (50) to establish the cell-firee synthesis of cyclosporin A were not successful, but they led to a partially enriched enzyme that could synthesize the diketopipcr-... 

Nonribosomal peptide synthesis means that the peptide is not produced by the tRNA-mRNA mechanism described in Chapter 28, Section 28.6. Each amino acid found in 224 is directly selected for incorporation into the growing peptide chain by one of the domains of surfactin synthetase, shown with the pendant SH groups. Substrate activation occurs after binding the amino acid, and the enzyme catalyzes the formation of an aminoacyl adenylate intermediate using Mg2+-ATP and release of a cofactor. Subsequently, the amino acid-O-AMP oxoester is converted into a thioester by a nucleophilic attack of the free thiol-bound cofactor of an adjacent PCP domain. (Note that ATP is adenosine triphosphate and AMP is adenosine monophosphate see Chapter 28, Section 28.5.)... 

Apart from dietary intake, riboflavin is also obtained from endogenous synthesis by microflora in the large intestine and is subsequently absorbed. Inside the cell, FMN is formed from vitamin B2 via adenosine triphosphate (ATP) phosphorylation and a flavokinase. FMN can be subsequently converted to FAD through a FAD synthetase also in the presence of ATP (Figure 37. IB). 

ScHUEGRAF, A., Ratner, S. and Warner, R. C. (1960) Free energy changes of the argininosuccinate synthetase reaction and of the hydrolysis of the inner pyrophosphate bond of adenosine triphosphate. J. Biol. Chem. 235, 3597-3602. 

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