Amino acid depletion

Shimoyama A. and Harada K. (1984) Amino acid depleted carbonaceous chondrites (C2) from Antarctica. Geochem. J. 18, 281-286. 

New Directions in Tumor Therapy -Amino Acid Depletion with ClutaDON ... 

A new amino acid depleting anticancer drug approach. ASCO 2003. 

Ames test 1632 Amevive 454—455, 1119 Amiloride 1525 Amino acid depletion... 

Variations in the level of aminoacylation of tRNA arising from the altered specificity of an aminoacyl-tRNA synthetase or from an amino acid depletion would be expected to exert a profound effect on the rate and level of protein synthesis. There are reports that qualitative changes in aminoacyl-tRNA synthetases may occur during embryo development [58] and in different tissues and organs [15] and that multiple synthetases may occur [59]. However, with the knowledge that mitochondria contain unique synthetases, a reexamination of these data in terms of the localization of the enzymes would help in clarification. 

In nucleotide-depleted yeast, protein synthesis and amino acid incorporation is dependent on and is proportional to the amount of added purines and pyrimidines, which serve as precursors for RNA (379). Conversely, in amino acid-depleted S. aureus, RNA and protein synthesis both are dependent on and proportional to the amount of added amino acids (411). Furthermore, as we have already seen, no synthesis of protein takes place in pyrimidineless mutants in the absence of the missing RNA precursors and, conversely, no synthesis of RNA takes place in amino acid auxotrophs in the absence of the missing amino acid (412-416). The dependence of RNA synthesis on the presence of amino acids was also established for animal systems (liver) by Munro and co-workers (4l7, 418). 

Lipase-catalyzed methanolysis of racemic N-benzyloxycarbonyl (Cbz) amino acid trifluoroethyl esters carrying aliphatic side chains afforded the L-methyl esters and the D-trifluoromethyl esters (Figure 6.16). The released alcohol (CF3CH2OH) is a weak nucleophile that cannot attack the ester product. The nucleophilidty of the leaving group is depleted by the presence of an electron-withdrawing group [63]. 

Carnivores rely on a protein-rich diet and produce new biomass primarily from dietary amino acids, although the enzymes required for de novo amino acid synthesis are present (Garmes et al., 1998). Bone collagen, muscle (meat) and apatite were analyzed for a set of modern southern African herbivores and carnivores (Lee-Thorp et al., 1989). The isotopic analyses showed i C enrichment in bone collagen, apatite and muscle, and depletion in lipids. Difference in values between herbivores and carnivores indicates a trophic effect, which for carbon in bone collagen is 2.5-3%o (Fig. 2). 

Six compounds have vitamin Bg activity (Figure 45-12) pyridoxine, pyridoxal, pyridoxamine, and their b -phosphates. The active coenzyme is pyridoxal 5 -phos-phate. Approximately 80% of the body s total vitamin Bg is present as pyridoxal phosphate in muscle, mostly associated with glycogen phosphorylase. This is not available in Bg deficiency but is released in starvation, when glycogen reserves become depleted, and is then available, especially in liver and kidney, to meet increased requirement for gluconeogenesis from amino acids. 

The target of mupirocin is one of a group of enzymes which couple amino acids to their respective tRNAs for delivery to the ribosome and incorporation into protein. The particular enzyme inhibited by mupirocin is involved in producing isoleucyl-tRNA. The basis for the inhibition is a structural similarity between one end of the mupirocin molecule and isoleucine. Protein synthesis is halted when the ribosome encounters the isoleucine codon through depletion of the pool of isoleucyl-tRNA. 

L-Asparaginase, an enzyme derived from E. coli or Erwinia carotovora, has been employed in cancer chemotherapy where its selectivity depends upon the essential requirement of some tumours for the amino acid L-asparagine. Normal tissues do not require this amino acid and thus the enzyme is administered with the intention of depleting tumour cells of asparagine by converting it to aspartic acid and ammonia. Whilst L-asparaginase showed promise in a variety of experimentally induced tumours, it is only useful in humans for the treatment of acute lymphoblastic leukaemia, although it is sometimes used for myeloid leukaemia. 

All the disorder-specific depletions except one are, from the leftmost, typically buried amino acids. The one exception, N, is out of place in being both a surface-preferring and an order-promoting residue. Perhaps the short side chain, with its propensity to hydrogen-bond to the backbone (Presta and Rose, 1988 Richardson and Richardson, 1988), tends to induce local structure. This order-inducing tendency might explain the out-of-place behavior of N. 

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