3 -Phosphoadenosine-5 -phosphosulphate

JAIN, J.C., GROOTWASSINK, J.W.D., KOLENOVSKY, A.D., UNDERHILL, E.W., Purification and properties of 3-phosphoadenosine-5-phosphosulphate desulphoglucosinolate sulphotransferase from Brassica juncea cell cultures, Phytochemistry, 1990, 29, 1425-1428. 

Conjugation with sulphate, catalyzed by cytosolic sulphotrans-ferases, is also a major route of Phase 11 metabolism, where inorganic sulphate, made available in the activated form of 3 -phosphoadenosine-5 -phosphosulphate (PAPS), is added to the molecule (Fig. 1). This is the most important pathway in the metabolism of phenols and is a very efficient conjugating system as long as inorganic sulphate is avaUahle. 

In contrast to these conjugation reactions, the formation of sulphate esters is probably an extramicrosomal process, catalysed by relevant enzymes in the presence of the coenzyme 3-phosphoadenosine-5-phosphosulphate. In this case, sulphuric acid is conjugated with primary aliphatic alcohols to produce alkyl sulphates, which are normal components of urine. 

Sulfation, using 3 -phosphoadenosine-5 -phosphosulphate (PAPS) as cofactor, is rarely a primary clearance mechanism for drugs relative to glucuronidated drugs or those cleared by cytochrome P450 enzymes. Exceptions include minoxidil, acetaminophen at therapeutic doses, and ethinylestradiol. Recombinant enzymes are commercially available for sulfotransferase phenotyping (Schneider and Glatt, 2004), but selective inhibitors have yet to be identified. 

C. Sulphation Sulphotransferases, e.g. phenol and steroid alcohol sulphotransferase Mainly phenols but also alcohols, amines and thiols ROH + 3 -phosphoadenosine-5 -phosphosulphate (PAPS) R-OSO3H + ADP... 

Sulphatide is an important constituent of the myelin sheath of nervous tissue and the incorporation of radioactive sulphate into the sulphatide molecule has been used to study myelination. The donor of the sulphate group is the complex nucleotide 3 -phosphoadenosine 5 -phosphosulphate, usually abbreviated in scientific papers to PAPS (Figure 7.10). PAPS itself is produced from ATP in two steps via an adenosine 5 -phosphosulphate (APS) intermediate. The synthesis of sulphatide is catalysed by a sulphotransferase which has been detected in the microsomal fraction from a number of tissues ... 

Figure 11.19 Sulpholipid synthesis and breakdown. Continuous lines show reactions that have been demonstrated dashed lines are possible pathways. Underlined compounds have been used in experiments on sulpholipid synthesis. APS, adenosine phosphosulphate PAPS, phosphoadenosine phosphosulphate. Adapted from Harwood (19806).

As expected the formation of sulphatides involves transfer of sulphate from phosphoadenosine phosphosulphate (PAPS). The latter is formed in a two-step reaction involving ATP and inorganic sulphate via an adenosine phosphosulphate (APS) intermediate. Galactosylceramide and lactosyl-ceramide were both acceptors for the sulphate from PAPS. Sulphatide synthesis is most rapid in the period 20-25 days after birth in rat brain (Stoffel, 1971). The sulphatides may be involved in the activity of the Na /K -ATPase (cf. Stoffel, 1971). 

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