Histidine naturally occurring

CfiHqNaO . M.p. 277 C. The naturally occurring substance is laevorotatory. Histidine is one of the basic amino-acids occurring in the hydrolysis products of proteins, and particularly of the basic proteins, the protamines and histones. It is an essential constituent of the food of animals. 

Histidine is one of the 20 naturally occurring amino acids commonly found in proteins (see Chapter 4). It possesses as part of its structure an imidazole group, a five-membered heterocyclic ring possessing two nitrogen atoms. The pAl for dissociation of the imidazole hydrogen of histidine is 6.04. 

The interaction with both synthetic and naturally occurring amino acids has been studied extensively glycine (138, 173, 219-221), a-(173, 219) and /3-alanine (138, 220), sarcosine (219), serine (222), aspartic acid (138, 173, 222-226), asparagine (222), threonine (222), proline (219), hydroxyproline (219), glutamic acid (138, 222-225), glutamine (222), valine (219, 227), norvaline (219), methionine (222, 226), histidine (228, 229), isoleucine (219), leucine (219, 230), norleu-cine (219), lysine (222), arginine (222), histidine methyl ester (228), phenylalanine (138, 222), tyrosine (222), 2-amino-3-(3,4-dihydroxy-phenyl jpropanoic acid (DOPA) (222), tryptophan (222), aminoiso-butyric acid (219), 2-aminobutyric acid (219,231), citrulline (222), and ornithine (222). 

N 092 "Hel ix-Coil Stability Constants for the Naturally Occurring Amino Acids in Water. 22. Histidine Parameters from Random... 

Buffers are often added to maintain a constant pH in biochemical research6 and naturally occurring buffer systems within body fluids and cells are very important (Box 6-A). Among the most important natural buffers are the proteins themselves, with the imidazole groups of histidine side chains providing much of the buffering capacity of cells around pH 7 (Figs. 3-1 and 3-2). Table 3-1 lists some useful biochemical buffers and their pKa values. Here are a few... 

The reader is referred to other chapters for the following heterocyclic systems ligands with mainly amine-type groups and one heterocyclic substituent (Chapter 13.1) polypyrazolyl compounds (Chapter 13.6) ligands that also contain another donor atom, such as O, S or P (Chapters 14, 20.3 and 20.4) macrocyclic ligands (Chapter 21) and naturally occurring ligands, such as histidine (Chapters 22 and 62). 

High-spin/low-spin transitions bipyridyl metal complexes, 90 iron complexes, 94 polypyridyl metal complexes, 91 Histamine metal complexes, 82 Histidine copper complexes naturally occurring, 965 metal complexes, 746 naturally occurring, 966 reactivity, 756 stereoselectivity, 754 Schiff bases... 

These superoxo complexes are relevant models for the naturally occurring oxygen carriers hemoglobin and myoglobin, which contain ferroprotoporphyrin IX as an active center in which the sixth axial postion is occupied by the imidazole moiety of histidine.17 They also intervene as primary oxygen adducts in enzymatic cytochrome P-450 oxygenases.18... 

The imidazole nucleus appears in a number of naturally occurring products, among which the most important are the amino acid histidine (203) and the purines, which comprise many of the important bases in nucleic acids. These purines, of which adenosine (204) is an example, are fused imidazopyrimidines. Their chemistry is discussed in Chapter 4.09. 

A final group of covalent small-molecule inhibitors of proteases are mechanism-based inhibitors. These inhibitors are enzyme-activated irreversible inhibitors, and they involve a two-hif mechanism that completely inhibits the protease. Some isocoumarins and -lactam derivatives have been shown to be mechanistic inhibitors of serine proteases. A classic example is the inhibition of elastase by several cephalosporin derivatives developed at Merck (Fig. 8). The catalytic serine attacks and opens the -lactam ring of the cephalosporin, which through various isomerization steps, allows for a Michael addition to the active site histidine and the formation of a stable enzyme-inhibitor complex (34). These mechanism-based inhibitors require an initial acylation event to take place before the irreversible inhibitory event. In this way, these small molecules have an analogous mechanism of inhibition to the naturally occurring serpins and a-2-macroglobin, which also act as suicide substrates. 

Naturally-occurring derivatives of histidine (methylhistidines and phosphohistidines) are described in 2.12.2. The carboxymethyl-histidines are the best characterized derivatives of histidine formed in proteins in vitro. 

Some naturally occurring amino acids are alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine. 

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