The main pathways of Cys metabolism to pyruvate proceed via eystemesulfuiate. CssC, mereaptopvruvate, or directly. Much smaller amounts of Cys are converted to taurine. L-alanine. and cysteamine.

Cysteinesulfmate: Cysteine dioxygenase (ECl. 13.11.20) with iron and FAD at its catalytic center oxidizes cysteine to cysteinesulfmate. mainly in the liver. The second step can be catalyzed by the PLP-dependent aspartate aminotransferase (EC2.6.1.11 in eytosol. The enzyme is generated by partial hydrolysis of aromatic amino acid cooh hjn-ch

CH3 L-Methionine cooh

CH3 L-Methionine

Cysteine dioxygenase |NAD(P). Fe)

1 Aspartate decarboxylase ch (PLP) Is sojh

Cysteamine L-Afanine

Sulfinoalaniney decarboxylase cooh I


Cystine reductase (nadh)/

GÍu tai h ione-c ysti ne transhyd rogenase

Cysteine dioxygenase |NAD(P). Fe)

\ giuiamate CysteineV' V-H. aminds n transieras e\

Cysteamine L-Afanine so3 h;,0 cooh

1 Aspartate decarboxylase ch (PLP) Is sojh

cooh I


Cysteamine dioxygenase>'Fe


CHj ch; so3h Taurine

Cysteamine dioxygenase>'Fe

dehydrogenase molybdopte rin+he me


Sulfinoalaniney decarboxylase


Aspartate amino-n-keto^v transferase gl uta rale \ (PLP)

Merca pto-pyruvate sulturtrans> 1 erase (Zn cooh 1

ch, cooh

s Thto-^ cysteine

Aspartate amino-n-keto^v transferase gl uta rale \ (PLP)


so t dehydrogenase molybdopte rin+he me



cooh I


Hgurr 8.51 Meiabottsm of L cysteine and L-cyttirte transferase (EC2.6.1.57). This cytosolic enzyme is not identical w ith the more abundant mitochondrial aspartate aminotransferase (EC2.6.1.11. The product of this reaction. bcta-sulfinyl pyruvate. decomposes spontaneously into sulfite and pyruvate. The potentially toxic sulfite can be converted to sulfate by sullite oxidase (EC1.8.3.1) in the mitochondrial intermembrane space. Sulfite oxidase contains both molybdenum cofactor and heme as prosthetic groups, and uses cytochrome c as an electron acceptor. Aspartate 4-decarboxylase (1X4.1.1.12) is present in mammalian tissues (Rat hod and Fellman, 1985). The desullinase activity of this PLP-dependent enzyme facilitates the conversion of cysteinesulfinate to sulfite and alanine.

Cystine. Cys can be converted to Cystine in most tissues by glutathione-cystine transhydrogenase (EC1.4.4) or cystine reductase (EC1.6.4,1) depending on the prevailing redox stale. Cleavage of thiocysteine by PLP-dependent cystathionine gamma-lyase (hi 4.4 1.1) generates thiocysteine, ammonia, and pyruvate. Nonenzymic hydrolysis of thiocysteine releases I'ys and persullide.

Mercuptopyruvate: Cysteine aminotransferase (El' catalyzes the PLP-dependent transfer of the I'ys amino group to oxoglutarate. The resulting 3-ntereap-topyruvate can then donate its persultide group to a protein (to insert iron- sulfur clusters), thiol compounds (for thiosulfate biosynthesis) or another acceptor (e.g. cyanide in generate thiocyanate): this reaction is Facilitated by the zinc enzyme mereaptopy-ruvate sulfurtransferase (EC2.8. 1.2).

Single-step conversion: Cystathionine gamma-lyasc (4.4. 1.1) can produce pyruvate by direct elimination of ammonia and pcrsultide from Cys. The relative contribution of this reaction lo Cys cutabolism is unclear.

Taurine synthesis: Oxidation by cysteine dioxygcnase (ECl.13.11.20) followed by decarboxylation (PLP-dependent sulfinoalanine decarboxylase. EC4.1.1,29). and oxidation again (molybdenum-cofactor-dependent hypotaurine dehydrogenase, ECl.8.1.3) convert Cys into taurine (see Taurine below in this chapter). Alternatively, the iron-enzyme cysteamine dioxygcnase (ECl. 13.11.19) can synthesize hypotaurine from cystcamine.


Most of the hotly's Cys is contained in functional peptides and proteins from where it is released as proteins are hydroly/cd during normal lissue turnover. Glutathione is an important example for such Cys-containing peptides with dual storage and antioxidant functions. The tripeptidc is produced in two steps. The first, rate-limiting step links L-glutamatc to Cys in an ATP-driven reaction catalyzed by gamma-gluiamylcysteine synthetase ( EC6.3.2.2). Glutathione synthase (EC6.3.2.3) then adds a glycine residue. Glutathione can be broken down again by the successive actions of gamma-glutamyl transpeptidase (EC2.3.2,2) and any of a number of alternative dipeptidases (e.g. EC3.13. IN,, or3.4.11.2).

Additional amounts of cystine are membrane-bound in lysosomes. The export from this compartment is an ATPasc-dependent process which involves the transmembrane protein cystinosin (Touchman et a!.. 2000).


Cys from renal ultrafiltrate is recovered in the proximal tubule via the sodium-dependent transporters ASC and 8 and the exchanger BAT1 rBAT. It is of note that only the latter also mediates uptake of CssC. Individuals with defective BAT! rBAT have cystinuria, nephrolithiasis and other complications, because they can recover Cys, but not its oxidized form. Di- and tripeptides are recovered via the proton, peptide cotransporter 2 ( PepT2. SLCI5A2). Export across the basolateral membrane can use the sodium-dependent transporter ASCT1 (only Cys) and the exchanger I.AT2/4F2. Most |X()%) ofthe sulfur from Cys (and Met) is excreted as sulfate, smaller amounts as taurine (Bella and Stipanuk, 1995). The amino groups are excreted mainly after incorporation into urea.


The complexity ofthe systems that maintain Cys homeostasis is becoming incrcas-tngly apparent. Regulation affects tissue uptake, metabolism (synthesis from Met and breakdown of Cys), and secretion from cells Us by astrocytes ¡11 brain). The phosphorylation of amino aeid exchangers BATI/(hu,+), I. ATI, and I..AT2 is under the control of cell signaling pathways; cAMP as well as phytoestrogens intliieiice the act i v ity of these transporters (Mi/oguchi et al., 2001t.

Understanding And Treating Autism

Understanding And Treating Autism

Whenever a doctor informs the parents that their child is suffering with Autism, the first & foremost question that is thrown over him is - How did it happen? How did my child get this disease? Well, there is no definite answer to what are the exact causes of Autism.

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