Biosynthesis, cysteine

Cyclopentenones. from 1.4-diketones. 886-887 Cyclopropane, angle strain in, 115 bent bonds in. 115 from alkenes. 227-229 molecular model of, 111. 115 strain energy of, 114 torsional strain in, 115 Cystathionine, cysteine from. 1177 Cysteine, biosynthesis of, 1177 disulfide bridges from, 1029 structure and properties of, 1018 Cytosine, electrostatic potential map of, 1104... 

Cysteine, tyrosine, and hydroxylysine are formed from nutritionally essential amino acids. Serine provides the carbon skeleton and homocysteine the sulfur for cysteine biosynthesis. Phenylalanine hydroxylase converts phenylalanine to tyrosine. 

Cysteine Biosynthesis Occurs by Sulfhydryl Transfer to Activated Serine... 

Figure 18.5. GSH biosynthesis and the cystathionine pathway for cysteine biosynthesis in liver and the protective functions of GSH.

E. coli CysQ protein. The EcCysQ gene was first identified as a required gene in cysteine biosynthesis (Neuwald et ah, 1992). Since PAP is an intermediate in assimilation of sulfate during cysteine biosynthesis, it has been speculated that the CysQ protein breaks down PAP to prevent toxic amounts from accumulating in the cell (Neuwald et ah, 1992). 

Many methanogenic archaeabacteria lack cysteinyl-tRNA synthetase (CysRS). Interestingly, a Class II enzyme called O-phosphoseryl-tRNA synthetase (SepRS) acylates tRNA with O-phosphoserine (Sep) to form Sep-tRNA , which is then converted to Cys-tRNA by the enzyme Sep-tRNA Cys-tRNA synthase (SepCysS). It has been proposed that this indirect pathway may be the sole route for cysteine biosynthesis in these organisms (9). The crystal structure of SepRS was recently... 

Sauerwald A, Zhu W, Major TA, Roy H, Palioura S, Jahn D, Whitman WB, Yates JR 3rd, Ibba M, Soil D. RNA-dependent cysteine biosynthesis in archaea. Science 2005 307 1969-1972. 

Grundy FJ, Henkin TM. The S box regulon a new global transcription termination control system for methionine and cysteine biosynthesis genes in gram-positive bacteria. Mol. Microbiol. 1998 30 737-749. 

Tandem copies of different classes of riboswitches can also promote response to multiple signals. For example, the Bacillus clausii metE gene, which encodes a B 12-independent form of methionine synthase, is regulated by tandem S box and B12 riboswitches. Expression is repressed by both SAM (which serves as an indicator that methionine pools are high) and B12 (which represses metE synthesis in favor of metH, which encodes the more efficient B 12-dependent form of the enzyme). Similarly, a cysteine biosynthesis operon in... 

The side chain of an amino acid can also be manipulated by biological catalysts. One example takes advantage of the natnrally broad snbstrate specificity of 0-acetylserine snlfhydrylase, the final enzyme in L-cysteine biosynthesis. This enzyme accepts a variety of alternative nucleophiles, in addition to the nsnal snlfide required for cysteine biosynthesis," to provide S-phenyl-L-cysteine... 

Present evidence indicates that the immediate precursor for cysteine is not serine itself, but rather OAS, and that cysteine biosynthesis proceeds by the reactions ... 

Equation (1) is catalyzed by serine acetyltransferase (E.C. 2.3.1.30) and Eq. (2) by cysteine synthase (E.C. 4.2.99.8). Evidence that these reactions represent the major pathway for cysteine biosynthesis is as follows (a) Serine acetyltransferase has been demonstrated in a number of plants (see Section II,B,1), and OAS is a natural constituent of cultured tobacco cells, being present at a concentration of at least 120 nmoles/g fresh weight (Smith, 1977). (b) Cysteine synthase has been demonstrated in a wide variety of plants. All such enzyme preparations show activities with OAS far in excess of those with serine (Section II,B,2). (c) The physiological role of the two enzymes is well established in microorganisms (Siegel, 1975), lending credence to their role in plants. 

The finding that OAS is the substrate for cysteine biosynthesis raises the question of the physiological role of serine sulfhydrase , the first enzyme reported able to synthesize cysteine. 

Fig. 2. Control of cysteine biosynthesis. Reactions are shown by heavy arrows. Only the bound pathway for sulfate reduction is shown. The intermediate carrier-S-S is shown in brackets because its physiological significance has not been established. The sites at which negative or positive control occur are shown by - or +, respectively. Thin arrows jndicate the relationship between effectors and their control sites.

An important proviso of this scheme is that under normal conditions the rate of synthesis of cysteine is limited by the availability of its sulfide precursor. Then, changes in the rate of formation of sulfide will be closely coupled to changes in the rate of cysteine formation. Evidence in support of the limitation of the rate of cysteine biosynthesis by the availability of sulfide includes the following, (a) The concentration of acid-volatile sulfide in L. minor growing on sulfate is about 11 fxM (Brunold and Schmidt, 1978), while the of cysteine synthase for sulfide is at least 180 f/M (Table II). This comparison suggests that cysteine synthase may normally be operating below its for sulfide, (b) Administration of H2S (18 ppm in the gas phase) to L. minor caused about a 50% increase in the steady-state concentration of soluble cysteine in the plants within a few minutes (Brunold and Erismann,... 

These lines of evidence suggest, but do not furnish compelling proof, that cysteine formation may ordinarily be limited by sulfide availability. Nevertheless, the discussion which follows of fiictors regulating the rate of sulfide production appears to be justified on the expectation that such regulation will probably be reflected by changes in the rate of cysteine biosynthesis. 

In addition to the major elfectors (AdoMet, threonine, and lysine), cysteine and isoleucine may participate in the control of methionine biosynthesis, at least in some plants. Both isoleucine and cysteine would be expected to accumulate as a result of the diversion of O-phosphohomoserine toward threonine. Isoleucine is a potent competitive inhibitor of the homoserine kinase of pea seedlings (Thoenef aL, 1978), but not that of barley seedlings (Aarnes, 1976). Cysteine inhibits homoserine dehydrogenase (see Bryan, this volume. Chapter 11) and can inhibit the stimulation by AdoMet of some (Madison and Thompson, 1976) but not all (Aarnes, 1978 Thoen et al., 1978) preparations of threonine synthase. Any regulatory effect of cysteine may, however, be of short duration since the combined mechanisms described in Section II,D for regulation of cysteine biosynthesis would be expected to restore the normal concentration of this amino acid. Details of the control of methionine biosynthesis by the major effectors AdoMet, threonine, and lysine are presented below. 

The second important feedback mechanism which has to be eliminated regulates the penultimate reaction in L-cysteine biosynthesis. The L-serine transacetylase CysE is normally inhibited effectively by the end-product L-cysteine (Kj 1 pM). Also for this enzyme various muteins were generated showing a very efficient decoupling of feedback regulation by the end-product. Most powerful is the mutant allel named cysE23 encoding a protein with a K value of 2.3 mM. ... 

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