Mammalian substrate specificity

Uptake of LCFAs across the lipid-bilayer of most mammalian cells occurs through both a passive diffusion of LCFAs and a protein-mediated LCFA uptake mechanism. At physiological LCFA concentrations (7.5 nM) the protein-mediated, saturable, substrate-specific, and hormonally regulated mechanism of fatty acids accounts for the majority (>90%) of fatty acid uptake by tissues with high LCFA metabolism and storage such as skeletal muscle, adipose tissue, liver,... 

Redmond, T.M. et al.. Identification, expression, and substrate specificity of a mammalian beta-carotene 15,15-dioxygenase, J. Biol. Chem., 276, 6560, 2001. Leuenberger, M.G., Engeloch-Jarret, C., and Woggon, W.D., The reaction mechanism of the enzyme-catalyzed central cleavage of beta-carotene to retinal, Ang. Chem. Int. Ed., 40, 2614, 2001. 

Redmond, T. M. et al. (2001). Identification, expression, and substrate specificity of a mammalian beta-carotene 15,15 -dioxygenase. J. Biol. Chem. 276(9) 6560-6565. 

Protein kinases differ in their cellular and subcellular distribution, substrate specificity and regulation. These properties determine the functional roles played by the very large number of protein kinases that have been found in mammalian tissues, most of which are known to be expressed in neurons [3]. The major classes of protein serine-threonine kinase in the brain, listed in Table 23-1, are covered in this chapter. The major classes of protein tyrosine kinases in the brain are discussed in Chapter 24. 

Zhang N, Liu L, Liu F, et al. NMR-based model reveals the structural determinants of mammalian arylamine N-acetyltransferase substrate specificity. J Mol Biol 2006 363(l) 188-200. 

The analysis of the cytochrome crystal structures reveals extensive differences among the mammalian and the human CYPs that may reflect the structural flexibility of these enzymes and therefore the broad substrate specificity observed. In general, the secondary elements and the overall structure of the CYP are conserved. Nevertheless, it seems that in most enzymes, the most flexible regions are located between the F-G helixes and the B-C loop. For example in the CYP2B4 apoprotein (lpo5) the... 

YPClp and YDClp have different substrate specificity such that YPClp prefers phytoceramide (phytoCer) over dihydroceramide (dhCer) whereas YDClp prefers dhCer over phytoCer, however, neither enzyme uses the most common mammalian type ceramide having a 4-5 trans double bond on the sphingoid base as substrate. Both enzymes have a narrow pH optimum of 9.4-10, hence, are classified as alkaline ceramidases. Calcium ions activate but are not absolutely required for the activities of both enzymes. and inhibit the activities of both enzymes. None of the sphingoid bases inhibit the activities of YPC Ip and YDClp. 

Adenine aminohydrolase has been found in micro-organisms, but not in mammalian cells, and the substrate specificities of the enzymes from Azotobacter vinelandii and Candida utilis were found to be similar [55, 56], Among other purines, 2-aminoadenine, A -aminoadenine, and 6-chloropurine were found to be substrates [55]. ... 

Lewis, D. F. V. (2000) On the recognition of mammalian microsomal cytochrome P450 substrates and their characteristics Towards the prediction of human p450 substrate specificity and metabolism. Biochem. Pharmacol. 60, 293-306. 

The substrate specificities of both mammalian and yeast hexo-kinases have been extensively studied (76,77). Nevertheless, work in this area continues both in the search for isoenzyme specific inhibitors and in increasingly detailed investigations of the catalytic mechanism. Recently potential transition state analogs PI-(adenosine-5 )-P3-glucose-6 triphosphate (Ap -glucose) and P1-(adenosine-5 )-P4-glucose-6 triphosphate (Ap.-giucose) were tested as inhibitors of four hexokinase isoenzymes. However, they were found to exhibit less affinity for the enzyme than either of the natural substrates alone (78). 

Many aminopeptidases are zinc metalloenzymes.521 They catalyze the specific hydrolysis of N-terminal amino acids from proteins and peptides, and usually have a broad substrate specificity. The zinc aminopeptidases from mammalian sources are oligomeric, with molecular weights greater than 200 000, and have two moles zinc per mole subunit. Enzymes from microbial sources are usually monomeric (40 000 molecular weight) with one or two moles Zn11. 

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