PAPS sulfohydrolase

Phosphoadenosine 5 -phosphosulfate (PAPS) is the well-known sulfate donor that occupies a central position in sulfate biochemistry (Balasubrama-nian and Bachhawat, 1970 DeMeoi, 1975 Farooqui, 1980b). It is hydrolyzed into PAP and sulfate by PAPS sulfohydrolase (Balasubramanian and Bachhawat, 1962). Nothing has been reported on the purification of this enzyme, but the crude enzyme preparation shows optimal activity at pH 6.0. It is activated by Co " " and Mn " " and inhibited by ADP, fluoride, and sulfhydryl compounds (Balasubramanian and Bachhawat, 1962). The desulfation of PAPS is a specific reaction. Arylsulfohydrolase A from chicken brain and rabbit kidney cortex does not hydrolyze PAPS to PAP (Farooqui and Bachhawat, 1972 Farooqui and Helwig, unpublished). Because PAPS sulfohydrolase has never been purified from any source, nothing is known about its physicochemical properties. 

Phosphosulfates may react with a nucleophile (Nu) in either of the two modes of P-O or S-O bond fission (Figure 2). If water is the nucleophile, both modes of fission result in the same hydrolysis products. Mechanistically, however, the enzymes that catalyze P—O fission may be regarded as phosphatases, while those that catalyze S—O fission are sulfohydrolases. In fact, many hydrolytic enzymes are assumed to be sulfohydrolases without mechanistic proof. The possibility that they might be phosphatases was suggested by Roy by taking account their metal ion dependency (4). Meanwhile, PAPS acts as the sulfate donor to numerous nucleophilic acceptors such as steroids and phenols. In such sulfate transfer reactions, S—O fission must occur. PAPS and APS also are known to act as the key intermediates in the reduction of sulfate to sulfite. Here again, the S—O fission may be the most probable mode. 

The role of the APS sulfohydrolases in sulfate metabolism is not understood precisely. The lysosomal APS sulfohydrolase can hydrolyze bis(4-nitro-phenyl) phosphate and 4-nitrophenyl 5 -phosphothymidine (Roger et al., 1978). Thus the lysosomal APS sulfohydrolase is less specific than its cytosolic counterpart, which does not hydrolyze these nitrophenyl derivatives. The apparent role of the lysosomal enzyme is to hydrolyze the acid anhydrides of such compounds as FAD, ATP, and ADP in secondary lysosomes. Thus lysosomal APS sulfohydrolase is an acid anhydride hydrolase that helps the cell in the recovery of nucleoside monophosphates from acid anhydrides. The APS sulfohydrolase in the cytosolic fraction probably regulates the concentrations of PAPS and therefore plays an important role in the control of sulfate conjugation. 

Bailey-Wood, R., Dodgson, K. S., and Rose, F. A., Purification and properties of two APS-sulfohydrolases from rat liver and their possible role in degradation of PAPS. Biochim. Biophys. Acta 220, 284-299 (1970). 

Fig. 2. Summary of the free and bound pathways of sulfate assimilation in plants. Some related reactions and points of entry of several forms of inorganic sulfur are also shown. The reaction sequence catalyzed by (1) ATP sulfurylase, (2) APS sulfotransferase, (3) thiosulfonate reductase, and (4) cysteine synthase constitutes the bound sulfate assimilation pathway. The synthesis of OAS is catalyzed by (5) serine transacetylase. The reaction sequence (I), (6)-(9)or (1), (2), (10), (8), (9) constitutes the free pathway reactims (7) and (10) are nonenzymatic, (6) is catalyzed by APS sulfotransferase, (8) by sulfite reductase, and (9) by cysteine synthase. APS and PAPS are interrelated via (11) APS kinase and (12) NDP phophohydrolase. APS can be hydrolyzed via (13) APS sulfohydrolase or (14) APS cyclase.

---