Cystine biosynthesis

Clausen T, Kaiser JT, Steegborn C, et al. 2000. Crystal structure of the cystine C-S lyase from Synechocystis stalibization of cysteine persulfide for FeS cluster biosynthesis. Proc Natl Acad Sci USA 97 3856-61. 

Reduction of the disulfide bond of cystine is used to activate enzymes of photosynthetic carbohydrate biosynthesis in plants. The reductant is a small protein called thioredoxin. Thioredoxin also serves as a reductant for the biosynthesis of deoxynucleotides in animals and microorganisms as well as in plants. 

The fiber surface is bounded by a thin membrane 100 A thick called the epicuticle. The cuticle is a scaly, tubular layer and consists of flattened cells which overlap to give a rachet-like profile to the fiber. Each scale cell contains two distinct layers, a keratinous outer layer termed the exocuticle and a nonkeratinous inner layer that appears to be derived from cytoplasmic debris and is termed the endocuticle. There is some evidence that the exocuticle itself is complex with an outer cystine-rich layer termed exocuticle a. In coarse fibers the cuticle may be many scale-cells thick and where the cells overlap they are separated by an intercellular layer formed during biosynthesis by the deposition of nonkeratinous protein between the cell membranes. This layer is sometimes referred to as intercellular cement. 

The ability of thiol groups to form disulfide bridges reversibly is essential in the biological reduction of sulfate and in the biosynthesis of cysteine (33) and methionine (34) fr°m cystine (35) (Scheme 23).4... 

Carbon atom 5 of the penicillins [as (198)] has been shown to derive from C-3 of cyst(e)ine [as (201)]. In feeding experiments with (2R, 3R)-[2,3- H2]cysteine, 2R, 3S)-[3- H]cysteine, and [3,3 - H2]cystine the fates of the hydrogen atoms originally present at C-3 of cysteine have been examined. As expected tritium label was to some extent lost from C-2 of cysteine. More importantly, retention of nearly one half of the tritium from [3,3 - H2]cystine indicated that hydrogen loss from C-3 was stereospecific. Further, high retention of tritium at C-5 of the penicillin G (199) derived from (2R, 3l )-[2,3- H2]cysteine and low retention in the experiment with (2R, 3S)-[3- H]cysteine demonstrates that it is the 3-pro-S hydrogen of cysteine which is lost in penicillin biosynthesis, and overall the transformation occurs with retention of configuration, as it does for valine. 

The more complex sulphur requirements of the marine animals are met largely by cysteine, cystine, methionine, biotin, and thiamine (Young and Maw, 1958) (Fig. 4). Cysteine is a component of the tripeptide glutathione and a precursor of taurine. Methionine is as an essential amino acid involved in biosynthesis of proteins, creatine and adrenaline. Adenosylmethionine is considered to be the active part in transmethylation, e.g. of choline. Methionine is part of the pathways to homocysteine, cystathionine and methylthioadenosine (Young and Maw, 1958). Various organisms convert cysteine and/or cystine into mercapturic acids, cysteine sulphinic acid, and thiazolidine derivatives (Zobell, 1963). 

Metabolic effects include interference with the biosynthesis of cystine and cholesterol, depression and stimulation of phospholipid synthesis and, at higher concentrations, inhibitions of serotonin oxidation. A 1981 study did not reveal any decrease in serum cholesterol or increase in serum triglycerides (Kiviluoto et al., 1981). 

The latter possibility was reconsidered more recently by Stijve (755, 765). According to his observations, psilocybin in Psilocybe semilance-ata ind in five Inocybe species was accompanied by its precursor baeo-cystine, which may indicate that during biosynthesis phosphorylation precedes methylation in conformity with the sequence tryptophan tryptamine — 4-hydroxytryptamine norbaeocystine baeocystine ... 

A similar enzyme has recently been purified 277-fold from turnip (R. rapa) roots (Anderson and Thompson, 1979). The properties of this enzyme appear to be very similar to those of the rutabaga except the purified enzyme had some activity towards DL-cystathionine and several other substituted cysteines. Even though the activity towards cystathionine is only 22% that of L-cystine and the A , for cystathionine was 4 mM as compared to 0.94 mM for L-cystine, these authors consider that this may have a j8-cystathionase function in methionine biosynthesis. 

CYP58 Epoxidation of o-methyl-sterigmato-cystin precursor and trichodiene C-2 hydroxylation, C12-C13 epoxidation, Cll and C3 hydroxylations Aflatoxin and trichothecene biosynthesis A. flavus, A. parasiticus , and F. gra-minearum, F. sporotrichoides [512, 836] [513, 514]... 

We investigated the biosynthesis of component amino acids of glutathione (GSH) in vitamin-Bi2 or folic-acid deficient rats (1). Glycine-2-C or L-cystine-S was administered intraperitoneally to normal or the deficient rats. Liver GSH was determined, then isolated, and the radioactivity of GSH and its component amino acids was determined. The extent of incorporation of either glycine-2-C or cysteine-S into the respective moieties of GSH was not appreciably affected by either deficiency, indicating that neither vitamin is involved in the sjrstems which catalyze the synthesis of GSH from glycine, cysteine, and glutamic acid, a conclusion which is in accord with those of Bloch (2) and Snoke and Rothman... 

Tests to determine the nature of the compounds formed from the decarboxylation of cystine that could undergo oxidation led to the observation that cystamine disulfoxide was oxidized with ease, whereas cystamine was completely resistant. From these observations, it was hypothesized that two oxidizing enzymes may be involved in the reaction, one oxidizing cystine to the disulfoxide, and one continuing the oxidation of the cystamine disulfoxide subsequent to the decarboxylation of the cystine disulfoxide. If it is assumed that the cystamine disulfoxide is simultaneously oxidized and cleaved to 2-aminoethanesulfinic acid, the oxidation scheme leads to the intermediate that was established for the biosynthesis of taurine from cysteine by Awapara. ... 

Creatine biosynthesis defects Lysosomal cystine transport def., infantile Lysosomal cystine transport def, adolescent Hyperoxaluria type 1 Malonyl-CoA decarboxylase def Lysosomal cystine transport def, infantile Lysosomal cystine transport def, adolescent... 

In order to confirm the role of serine the same workers administered a mixture of L-[U- C]-serine and L-[3- H]-serine to a C. violaceum fermentation. The resulting " C-labelled (34) showed 101% retention of the tritium label. Similarly, feeding a mixture of L-[3- C]-serine and L-[3- H]-serine resulted in 83% tritium retention in the product. However in two experiments where mixtures of L-[U- C]-cystine and L-[3,3 - H]-cysteine were fed only 14% and 20% of the tritium label was retained in the products. These experiments clearly indicated that serine is a closer precursor of (34) than cysteine. Again, the retention of tritium label from L-[3- H]-serine is reminiscent of nocardicin biosynthesis and suggests that the 3-lactam ring is closed by an Sjq2 displacement of the serine hydroxyl. 

The role of cysteine in penicillin biosynthesis was first demonstrated by Arnstein and Grant 210,211) who synthesised L- and D-cystine labelled in the P-position with or with or When these compounds were fed to cultures of Penicillium chrysogenum the L-isomer was found to be better incorporated into the resulting benzylpenicillin. Using a series of chemical degradations (Fig. 3), they were able to demonstrate the specific incorporation of cystine into benzylpenicillin. It was concluded that cystine is a direct precursor of penicillin, probably after reduction to cysteine. 

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