Thiols in Biochemistry

Thiols in Biochemistry.—As in previous volumes of these Reports, no attempt is made at comprehensive coverage in this section. However, there are relatively few topic areas linking to the general title of this section, and it is possible to indicate these with a few key references. 

Nara and K. Tuzimura, Agric. and Biol. Chem. [Japan), 1975, 39, 7. 

Machida, N. Ushijima, M. I. Machida, and Y. Kanaoka, Chem. andPharm. Bull. [Japan), 1975,23, 1385. 

Studies of addition of thiolates to flavans showing that addition to a 4a- or S-position of an isoalloxazine ring may be implicated in flavin catalysis of thiol-disulphide oxidation, are sufficiently broad to include dithiols and arenesulphinic acids.  

Of a number of thiols tested, mercaptoethanol was the most effective for the catalysis of the conversion of oleic acid - tra/w-9-octadecenoic acid. The compound (12 w = 1) was more effective than homologues n = 0, 2, or 3) in 

Thiols in Biochemistry.—Monoterpene keto-thiols (28, and the m-isomer) are the first of their type to appear in Nature. The major interest in biosynthesized thiols remains within the polypeptide field, and the identification, reactivity, and function of cysteine residues in polypeptides and proteins feature prominently in the literature. 

Photaki, J. Taylor-Papadimitriou, C. Sakarellos, P. Mazatakis, and L. 2 rvas, 

Thiols in Biochemistry.—Space available restricts the present coverage to a few key references. N-Acetyl-cysteine and -penicillamine react with adrenochrome to give the indolyl sulphides (18), (but see also ref. 650) while p-benzoquinone gives two diastereoisomers of (19) with L-cysteine ethyl ester.Other observations with possible significance 

Cysteine and cystine residues in proteins are converted into S-cyano-cysteine residues with 2-nitro 5-thiocyanatobenzoic acid, providing a point in the peptide chain at which selective cleavage can be performed.  

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Hiratsuka, T. (1987) Nucleotide-induced change in the interaction between the 20- and 26-kilodalton heavy-chain segments of myosin adenosine triphosphatase revealed by chemical cross-linking via the reactive thiol SH2. Biochemistry 26, 3168. 

Sutoh, K., and Hiratsuka, T. (1988) Spatial proximity of the glycine-rich loop and the SH2 thiol in myosin subfragment 1. Biochemistry 27(8), 2964-2969. 

Coenzyme A is another adenine nucleotide derivative, with its primary functional group, a thiol, some distance away from the nucleotide end of the molecule. This thiol plays an important role in biochemistry via its ability to form thioesters with suitable acyl compounds (see Box 7.18). We have seen how thioesters are considerably more reactive than oxygen esters, with particular attention being paid to their improved ability to form enolate anions, coupled with thiolates being excellent leaving groups (see Box 10.8). 

We have noted previously (see Section 2.1) the role played in biochemistry by the thiol disulfide interconversion, and the disulfide unit is a fundamental feature of the structure of peptides and proteins. The sulfur-sulfur bond between two cysteins link remote parts of a peptide chain or cross-link two such chains. Cleavage of these bonds in the hair protein keratin, followed by reoxidation, gives hair its desired shape. 

Ethanoic acid is activated for biosynthesis by combination with the thiol, coenzyme A (CoASH, Figure 18-7) to give the thioester, ethanoyl (acetyl) coenzyme A (CH3COSC0A). You may recall that the metabolic degradation of fats also involves this coenzyme (Section 18-8F) and it is tempting to assume that fatty acid biosynthesis is simply the reverse of fatty acid metabolism to CH3COSCoA. However, this is not quite the case. In fact, it is a general observation in biochemistry that primary metabolites are synthesized by different routes from those by which they are metabolized (for example, compare the pathways of carbon in photosynthesis and metabolism of carbohydrates, Sections 20-9,10). 

Bulaj G, Kortemme T, Goldenberg DP (1998) Ionization-reactivity relationships for cysteine thiols in polypeptides. Biochemistry 37 8965-8972... 

Well see later that the thiol-disulfide interconversion is extremely important in biochemistry, where disulfide l>ridges form the cross-links between protein chains that help stabilize the three-dimensional conformations of proteins. 

Thiocarboxylic esters do not play a major role in biochemistry, with the one exception of acetyl-CoA (4 R = Me), the prototype of acyl-CoAs (4), which represent important energy rich intermediates in amino acid, lipid and glucose metabolism. In fact the thiol esters (4) fit in with the scope of this chapter. They are often formed by acylation reactions and themselves react as acylating agents. 

Moss J, Stanley SJ, Watkins PA et al. (1986) Stimulation of the thiol-dependent ADP-ribosyltransferase and NAD glycohydrolase activities of Bordetella pertussis toxin by adenine nucleotides, phospholipids, and detergents. In Biochemistry 25 2720-2725... 

The known occurrences of thioaldehydes in biochemistry are few. One well-studied example is the involvement of a thioaldehyde in the decarboxylation of cysteine in phosphopantothenoyl-cysteine during coenzyme A biosynthesis. In the proposed mechanism for this decarboxylation, a thioaldehyde is generated at the cysteine sulfur by a flavin-dependent oxidation of the thiol. The resulting /3-thioketo acid, acting like a /3-keto acid, facilitates the decarboxylation of the amide-bound cysteine in phosphopantothenoyl-cysteine substrate. Finally, the flavinH2 produced in the thiol oxidation is used to reduce the thioaldehyde back to the thiol. 

Jeng, M.F., Holmgren, A., Dyson, H.J. Proton sharing between cysteine thiols in Escherichia coH thioredoxin Implications for the mechanism of protein disulfide reduction. Biochemistry 1995,34, 10101-5. 

Thiols have been of foremost importance in the development of the functional group concept in biochemistry. Because of its ease of... 

Reduction of disulphides to component thiols remains an important topic for study, and PhaP " or BusP " are suitable in aqueous media for reduction of disulphides and for preventing autoxidation of thiols on storage. Quantitative reduction of disulphides by an insolubilized thioP is an ingenious procedure likely to be much used in biochemistry. 

Lewis, S.D., Misra, D.C. and Shafer, J.A. (1980) Determination of interactive thiol ionizations in bovine serum albumin, glutathione, and other thiols by potentiometric difference titration. Biochemistry, 19, 6129-6180. 

M. Buck reviews in great depth the literature on self-assembled monolayers (SAMs) of thiols on gold, a classic means of surface modification. The wide variety of functional groups that is provided by synthetic chemists makes thiol-SAMs an exciting playground for applications where the gap between two worlds, the inorganic and the organic, needs to be closed. Examples are molecular electronics and biochemistry. 

Que BG, Downey KM, So AG (1980) Degradation of deoxyribonucleic acid by a 1,10-phenanthroline-copper complex the role of hydroxyl radicals. Biochemistry 19 5987-5991 Quintiliani M (1983) Cellular thiols and radiation response. In Balzani V (ed) Baxendale Memorial Symposium. Lo Scarabeo, Bologna, pp 81-108... 

Pinter, M., and Friedrich, P., 1988, The calcium dependent proteolytic system calpain-calpatatin in Drosophila melanogaster, Biochem J., 253, 467-473 Pinter, M., Stierandova, A., and Friedrich, P., 1992, Purification and characterization o a Ca2 activated thiol protease from drosophila melanogaster, Biochemistry, 31, 8201-8206 Pontremoli, S., Melloni, E., Michetti, M., Salamino, F., Sparatore, B., Horecker, B., 1988, An endogenous activator of the Ca2+ -dependent proteinase of human neutrophils that increases its affinity for Ca2+, Proc. Natl. Acad. Sci., USA, 85, 1740-1743... 

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