Enzymological Aspects of Steroid Conjugation

Roy, A.B.

doi:10.1007/978-3-642-49793-3_2

Cited by 14 publications

(10 citation statements)

References 187 publications

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“…Sulfonation also has a significant role in the biotransformation of many endogenous low-molecular-weight compounds, including catecholamines (13), iodothyronines (14), and vitamin C (15). Likewise, sulfonation is an important modification of cholesterol (16) and its derivatives, bile acids (17), vitamin D (18,19), and steroids (20).…”

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confidence: 99%

Sulfonation and Molecular Action

2002

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The sulfonation of endogenous molecules is a pervasive biological phenomenon that is not always easily understood, and although it is increasingly recognized as a function of fundamental importance, there remain areas in which significant cognizance is still lacking or at most minimal. This is particularly true in the field of endocrinology, in which the sulfoconjugation of hormones is a widespread occurrence that is only partially, if at all, appreciated. In the realm of steroid/sterol sulfoconjugation, the discovery of a novel gene that utilizes an alternative exon 1 to encode for two sulfotransferase isoforms, one of which sulfonates cholesterol and the other pregnenolone, has been an important advance. This is significant because cholesterol sulfate plays a crucial role in physiological systems such as keratinocyte differentiation and development of the skin barrier, and pregnenolone sulfate is now acknowledged as an important neurosteroid. The sulfonation of thyroglobulin and thyroid hormones has been extensively investigated and, although this transformation is better understood, there remain areas of incomplete comprehension. The sulfonation of catecholamines is a prevalent modification that has been extensively studied but, unfortunately, remains poorly understood. The sulfonation of pituitary glycoprotein hormones, especially LH and TSH, does not affect binding to their cognate receptors; however, sulfonation does play an important role in their plasma clearance, which indirectly has a significant effect on biological activity. On the other hand, the sulfonation of distinct neuroendocrine peptides does have a profound influence on receptor binding and, thus, a direct effect on biological activity. The sulfonation of specific extracellular structures plays an essential role in the binding and signaling of a large family of extracellular growth factors. In summary, sulfonation is a ubiquitous posttranslational modification of hormones and extracellular components that can lead to dramatic structural changes in affected molecules, the biological significance of which is now beginning to be appreciated.

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Sulfonation and Molecular Action

2002

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“…The enzymes that catalyze the formation of PAPS (chemical structure depicted in Fig. 1), such as the steroid sulfotransferases, are present in the cy tosolic fraction of tissue preparations (7). The activation of inorganic sulfate to form PAPS results from the concerted action of two enzymes (28)(29)(30) The first step is catalyzed by ATP sulfurylase (ATP: sulfate adenylyltransferase, EC 2.7.7A) and involves the reaction of inorganic sulfate with ATP to form adenosine 5'-phosphosulfate (APS) and inorganic pyrophosphate (PP t ).…”

Section: B Synthesismentioning

confidence: 99%

“…Sulfotransferases, the enzymes that catalyze the sulfoconjugation of steroids, are typically isolated from the high speed soluble fraction of tissue preparations (7). Moreover, the enzymes that sulfoconjugate other relatively small endogenous compounds, such as catecholamines, iodothyronines, vitamin D, bile acids, and ascorbate, as well as the enzymes that sulfoconjugate xenobiotics, are also present in the cell sap (8,9).…”

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confidence: 99%

Steroid Sulfotransferases

Strott¹

1996

Endocrine Reviews

162

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“…1,2 Sulphated glycosaminoglycans, glycolipids, glycoproteins and hydroxysteroids are hydrolysed by sulphatases, each of which has exquisite specificity towards its individual substrate in vivo. 3,4 A subset of sulphatases, each with very different natural substrates, is active in vitro against a common set of small aromatic substrates, hence the name arylsulphatases. This functional correlation reflects a high degree of predicted amino acid sequence similarity along the entire length of the enzymes.…”

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Molecular and biochemical characterisation of a novel sulphatase gene: Arylsulfatase G (ARSG)

et al. 2002

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Molecular analysis has provided important insights into the biochemistry and genetics of the sulphatase family of enzymes. Through bioinformatic searches of the EST database, we have identified a novel gene consisting of 11 exons and encoding a 525 aa protein that shares a high degree of sequence similarity with all sulphatases and in particular with arylsulphatases, hence the tentative name Arylsulfatase G (ARSG). The highest homology is shared with Arylsulfatase A, a lysosomal sulphatase which is mutated in metachromatic leukodistrophy, particularly in the aminoterminal region. The 10 amino acids that form the catalytic site are strongly conserved. The murine homologue of Arylsulfatase G gene product shows 87% identity with the human protein. To test the function of this novel gene we transfected the full-length cDNA in Cos7 cells, and detected an Arylsulfatase G precursor protein of 62 kDa. After glycosylation the precursor is maturated in a 70 kDa form, which localises to the endoplasmic reticulum. Northern blot analysis of Arylsulfatase G revealed a ubiquitous expression pattern. We tested the sulphatase activity towards two different artificial substrates 4-methylumbelliferyl (4-MU) sulphate and p-nitrocatechol sulphate, but no arylsulphatase activity was detectable. Further studies are needed to characterise the function of Arylsulfatase G, possibly revealing a novel metabolic pathway.

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Enzymological Aspects of Steroid Conjugation

Cited by 14 publications

References 187 publications

Sulfonation and Molecular Action

Sulfonation and Molecular Action

Steroid Sulfotransferases

Molecular and biochemical characterisation of a novel sulphatase gene: Arylsulfatase G (ARSG)

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