Methionine in proteins

Fig. 16. Spherical polar coordinate system used to define metal ion (M) interactions with the side chain of methionine. In proteins the average polar angle d is 38°, and the average longitudinal angle is 169°. [Reprinted with permission from Chakrabarti, P. (1989) Biochemistry 28, 6081-6085. Copyright 1989 American Chemical Society.]...

Electrophiles can be hard or soft. Thus hard electrophiles react with nucleophilic sites in molecules such as O, N, C in nucleic acids or the S in methionine in proteins. Hard electrophiles are typically genotoxic such as the benzo(a)pyrene diol epoxide (see chap. 7). 

The consequence of sequence changes at the DNA level on the sequence of encoded protein is shown by the example in Table 2.3, where an AUG codon representing methionine in proteins is subjected to single base changes. The various types of mutations and their influence on information transfer are illustrated in Box 2.1. 

Besides thiol repair there also exists direct repair for one of the oxidation products of methionine, methionine sulfoxide. The enzyme peptide methionine sulfoxide reductase reduces the methionine sulfoxide formed in proteins due to oxidation and is therefore able to reconstitute the normal protein (Fig. 3). Besides methionine sulfoxide there exists a further oxidation product of methionine, methionine sulfone, which can not be repaired. The cycle of methionine oxidation and efficient methionine sulfoxide repair, and the early and easy oxidation of the methionine in proteins, led some authors to hypothesize that methionine acts as an intramolecular antioxidant for some proteins and so protects other amino acids from oxidation [12]. Besides the peptide methionine sulfoxide reductases, there also exists methionine reductases able to... 

Homogenization markedly reduces the propensity to oxidative rancidity, perhaps due to redistribution of the susceptible lipids and pro-oxidants of the MFGM (however, the propensity to hydrolytic rancidity and sunlight oxidized flavour (due to the production of methional from methionine in protein) is increased). 

The biological importance of the second thiol amino add, homocysteine, is as the thioether and sulphonium ion derivatives. The free thiol occurs only as a metabolic intermediate. Methionine, the methyl thioether, is one of the twenty amino adds utilized for protein synthesis. Our concepts of the special significance of methionine in protein structure and function are only beginning to be developed, and will not be considered here. N-Formyl methionine also has the distinctive role of being a chain initiator in protein synthesis. The most extensively studied form of this thiol is S-adenosyl methionine or SAM, the sulphonium ion cofactor. This is the principal methylating reagent of biological systems and other alkyl transfers from the sulphonium ion are also known. 

Sulfoxide hGH. Methionine residues in proteins are susceptible to oxidation primarily to the sulfoxide. Both pituitary-derived and biosynthetic hGH undergo sulfoxidations at Met-14 and Met-125 (29). Oxidation at Met-170 has also been reported in pituitary but not biosynthetic hGH. Both desamido hGH and Met-14 sulfoxide hGH exhibit full biological activity (29). 

Sulfur. Sulfur is present in every cell in the body, primarily in proteins containing the amino acids methionine, cystine, and cysteine. Inorganic sulfates and sulfides occur in small amounts relative to total body sulfur, but the compounds that contain them are important to metaboHsm (45,46). Sulfur intake is thought to be adequate if protein intake is adequate and sulfur deficiency has not been reported. Common food sources rich in sulfur are Hsted in Table 6. 

Of the twenty amino acids that are normally found in proteins, only two contain sulfur, cysteine and methionine. Cysteine has long been recognized as being easily oxidized and this oxidation is associated with the loss of biological activity of many proteins. In recent years, it has been shown that methionine also shares these characteristics. Methionine was first isolated by Mueller19 and was one of the last amino acids discovered. Its structure was later proven to be y-methylthio-a-aminobutyric acid by Barger and Coyne20 who named the amino acid methionine as a contraction for its chemical name. 

TABLE 1. Chemical oxidation of methionine in HL-60 cell proteins previously uniformly labeled with [35S]methionine ... 

The terms first, second, and third nucleotide refer to the individual nucleotides of a triplet codon. U, uridine nucleotide C, cytosine nucleotide A, adenine nucleotide G, guanine nucleotide Term, chain terminator codon. AUG, which codes for Met, serves as the initiator codon in mammalian cells and encodes for internal methionines in a protein. (Abbreviations of amino acids are explained in Chapter 3.)... 

Two amino acids—cysteine and tyrosine—can be synthesized in the body, but only from essential amino acid ptecutsots (cysteine from methionine and tyrosine from phenylalanine). The dietary intakes of cysteine and tytosine thus affect the requirements for methionine and phenylalanine. The remaining 11 amino acids in proteins are considered to be nonessential or dispensable, since they can be synthesized as long as there is enough total protein in the diet—ie, if one of these amino acids is omitted from the diet, nitrogen balance can stiU be maintained. Howevet, only three amino acids—alanine, aspartate, and glutamate—can be considered to be truly dispensable they ate synthesized from common metabolic intetmediates (pyruvate, ox-... 

As noted above, the presence of Met(O) in proteins would go undetected after acid hydrolysis and subsequent amino acid analysis. Thus, since this method of hydrolysis is most commonly used, it is impossible to ascertain from the literature the abundance of Met(O) residues normally present in proteins. However, a number of studies have reported the presence of Met(O) residues in various proteins using one of the appropriate procedures described above. It has been found that Met(O) residues comprise 30% of the total Met in proteins isolated from bovine glomerular basement membranes and anterior lens . Other investigators have reported that the levels of Met(O) in proteins of the trabecular meshwork of human eyes increased with the age of the donor . The amount of Met(O) detected ranged from 15% (10 years old) to 55% (79 years old) of the total methionine content found in the tissue samples. Other studies have shown that in certain species of clams the proteins of the hinge ligament contain only Met(0) residues and no Met . In addition, it has also been reported that as much as 18% of the Met residues in pea seed proteins is in the form of Met(O) . Lastly, Met(O) residues have been found in... 

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