This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
Synonyms: sulfation pathway
|Superclasses:||Activation/Inactivation/Interconversion → Activation|
|Degradation/Utilization/Assimilation → Inorganic Nutrients Metabolism → Sulfur Compounds Metabolism|
The sulfonation of biological compounds (sulfoconjugation) is a fundamental metabolic process, in which a sulfate group is added to an oxygen moiety to form a sulfate ester bond. The sulfonation of biomolecules occurs widely and results in a dramatic change in the physicochemical property of the sulfonated compounds [Huxtable86]. Sulfonated macromolecules such as a glycosaminoglycan, heparin or a glucosinolate are involved in many important processes, such as cell adhesion, hemostasis, the viscoelastic properties of connective tissue, and plant defense mechanisms. The sulfonation of tyrosine residues has been established as a post-translational modification for many secretory and membrane proteins (see protein-tyrosine sulfotransferase 1) and sulfated versions of lipids such as sphingolipids and galactoglycerolipids are found in the brain, peripheral nerves, and reproductive tissues of mammals. In addition, sulfoconjugation is important in the biotransformation of many low molecular weight compounds such as neurotransmitters and hormones, including catecholamines, iodothyronines, and steroids, and in the production of plant secondary metabolites, such as glucosinolates. Another role for sulfonation is the detoxification and removal of drugs and xenobiotics compounds [Venkatachalam98].
About This Pathway
In the course of sulfonation, inorganic sulfate must be activated prior to being transferred to an acceptor molecule [Gregory60]. In many organisms, including plants and mammals, 3'-phosphoadenylyl-sulfate (PAPS) is used as the universal sulfonate donor for all sulfotransferase reactions [Robbins58, Farooqui80].
The activation of inorganic sulfate to form PAPS is achieved by the concerted action of two enzymes. The first step is catalyzed by EC 126.96.36.199, sulfate adenylyltransferase (also known as ATP-sulfurylase) and involves the reaction of inorganic sulfate with ATP to form adenosine 5'-phosphosulfate (APS) and inorganic pyrophosphate (PPi). This enzyme has an unfavorable equilibrium (Keq ~ 10-7 M) in the direction of APS formation, and it has been postulated that the reaction is driven by the hydrolysis of PPi by a ubiquitous inorganic pyrophosphatase [Segel87]. In Escherichia coli K-12 it was found that the enzymes couples the formation of APS to hydrolysis of GTP [Liu94a].
The second step is catalyzed by EC 188.8.131.52, adenylyl-sulfate kinase, and involves the reaction of APS with ATP to form PAPS and ADP.
It should be mentioned that in plants most of the APS is used for biosynthesis of L-cysteine and L-methionine via the further reduction of APS to sulfide (see sulfate reduction II (assimilatory)). In mammals, however, all of the APS is converted to PAPS and used for sulfonation.
In bacteria, fungi, yeast and plants the two enzymes are found as separate polypeptide chains. In mammals the enzymes are physically linked on a single bifunctional protein [Lyle94].
For an extensive list of sulfonation reactions using 3'-phosphoadenylyl-sulfate, please look at that compound's page.
Superpathways: sulfate reduction I (assimilatory) , superpathway of L-methionine biosynthesis (by sulfhydrylation) , superpathway of sulfate assimilation and cysteine biosynthesis , superpathway of sulfur amino acid biosynthesis (Saccharomyces cerevisiae)
Hovingh70: Hovingh P, Linker A (1970). "The enzymatic degradation of heparin and heparitin sulfate. 3. Purification of a heparitinase and a heparinase from flavobacteria." J Biol Chem 245(22);6170-5. PMID: 5484472
Lyle94: Lyle S, Stanczak J, Ng K, Schwartz NB (1994). "Rat chondrosarcoma ATP sulfurylase and adenosine 5'-phosphosulfate kinase reside on a single bifunctional protein." Biochemistry 33(19);5920-5. PMID: 8180221
Murphy04: Murphy KJ, Merry CL, Lyon M, Thompson JE, Roberts IS, Gallagher JT (2004). "A new model for the domain structure of heparan sulfate based on the novel specificity of K5 lyase." J Biol Chem 279(26);27239-45. PMID: 15047699
Venkatachalam98: Venkatachalam KV, Akita H, Strott CA (1998). "Molecular cloning, expression, and characterization of human bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthase and its functional domains." J Biol Chem 273(30);19311-20. PMID: 9668121
Abola99: Abola AP, Willits MG, Wang RC, Long SR (1999). "Reduction of adenosine-5'-phosphosulfate instead of 3'-phosphoadenosine-5'-phosphosulfate in cysteine biosynthesis by Rhizobium meliloti and other members of the family Rhizobiaceae." J Bacteriol 181(17);5280-7. PMID: 10464198
Dahl90: Dahl, C., Koch, H., Keuken, O., Trueper, H.G. (1990). "Purification and characterization of ATP sulfurylase from the extremely thermophilic archaebacterial sulfate-reducer, Archaeoglobus fulgidus." FEMS Microbiol. Let. 67: 27-32.
DiazMejia09: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114
Frederiksen03: Frederiksen TM, Finster K (2003). "Sulfite-oxido-reductase is involved in the oxidation of sulfite in Desulfocapsa sulfoexigens during disproportionation of thiosulfate and elemental sulfur." Biodegradation 14(3);189-98. PMID: 12889609
Gavel98: Gavel OY, Bursakov SA, Calvete JJ, George GN, Moura JJ, Moura I (1998). "ATP sulfurylases from sulfate-reducing bacteria of the genus Desulfovibrio. A novel metalloprotein containing cobalt and zinc." Biochemistry 1998;37(46);16225-32. PMID: 9819214
Hatzfeld00: Hatzfeld Y, Lee S, Lee M, Leustek T, Saito K (2000). "Functional characterization of a gene encoding a fourth ATP sulfurylase isoform from Arabidopsis thaliana." Gene 2000;248(1-2);51-8. PMID: 10806350
Leustek94: Leustek T, Murillo M, Cervantes M (1994). "Cloning of a cDNA encoding ATP sulfurylase from Arabidopsis thaliana by functional expression in Saccharomyces cerevisiae." Plant Physiol 1994;105(3);897-902. PMID: 8058839
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