SULFATION PATHWAYS: Insights into steroid sulfation and desulfation pathways

Foster, Paul A.; Mueller, Jonathan Wolf

doi:10.1530/jme-18-0086

Cited by 41 publications

(50 citation statements)

References 125 publications

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“…Sulfation is another form of vitamin D phase II metabolism by sulfotransferase (SULT) enzymes. The major circulating sulfation metabolite is 25OHD3‐3‐ O ‐sulfate (Figure ) which has comparable circulating concentration ranges with unconjugated 25OHD3 . SULT2A1 is the major sulfating enzyme of 25OHD3 at the C3‐position of 25OHD3 which binds to DBP with high affinity .…”

Section: Vitamin D Conjugationmentioning

confidence: 99%

“…The most abundant sulfated form in urine was 25OHD3‐sulfate . Owing to the high circulating levels of 25OHD3‐3‐ O ‐sulfate, these levels should also be taken into account in determining vitamin D status owing to the role as a reservoir for 25OHD3 generation …”

Section: Vitamin D Conjugationmentioning

confidence: 99%

“…The major circulating sulfation metabolite is 25OHD3-3-O-sulfate ( Figure 8) which has comparable circulating concentration ranges with unconjugated 25OHD3. [136][137][138][139] SULT2A1 is the major sulfating enzyme of 25OHD3 at the C3-position of 25OHD3 which binds to DBP with high affinity. 136 Sulfation activity of 25OHD3 occurs in the kidney, liver, lung, and small intestine tissues.…”

Section: Vitamin D Conjugationmentioning

confidence: 99%

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The vitamin D metabolome: An update on analysis and function

Jenkinson

2019

Cell Biochemistry & Function

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Current understanding of vitamin D tends to be focussed on the measurement of the major circulating form 25‐hydroxyvitamin D3 (25OHD3) and its conversion to the active hormonal form, 1α,25‐dihydroxyvitamin D3 (1α,25(OH)2D3) via the enzyme 25‐hydroxyvitamin D‐1α‐hydroxylase (CYP27B1). However, whilst these metabolites form the endocrine backbone of vitamin D physiology, it is important to recognise that there are other metabolic and catabolic pathways that are now recognised as being crucially important to vitamin D function. These pathways include C3‐epimerization, CYP24A1 hydroxylase, CYP11A1 alternative metabolism of vitamin D3, and phase II metabolism. Endogenous metabolites beyond 25OHD3 are usually present at low endogenous levels and may only be functional in specific target tissues rather than in the general circulation. However, the technologies available to measure these metabolites have also improved, so that measurement of alternative vitamin D metabolic pathways may become more routine in the near future. The aim of this review is to provide a comprehensive overview of the various pathways of vitamin D metabolism, as well as describe the analytical techniques currently available to measure these vitamin D metabolites.

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Section: Vitamin D Conjugationmentioning

confidence: 99%

Section: Vitamin D Conjugationmentioning

confidence: 99%

Section: Vitamin D Conjugationmentioning

confidence: 99%

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The vitamin D metabolome: An update on analysis and function

Jenkinson

2019

Cell Biochemistry & Function

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“…4). Hence, any new insight on one class of these sulfotransferases may have direct applicability to the other (43).…”

Section: Arabidopsis and The Human Sulfotransferase Repertoirementioning

confidence: 99%

“…These insights mainly include discoveries of novel mechanisms of regulation (43). For example, the flexibility of the main substrate-binding loops-elucidated in part with new analytical and computational tools-is the molecular basis for the broad specificity of the sulfotransferase SULT1A1 (72), with possible implication also for AtSOT12 described below.…”

Section: Arabidopsis and The Human Sulfotransferase Repertoirementioning

confidence: 99%

Sulfation pathways from red to green

Günal

Hardman

Kopriva

et al. 2019

Journal of Biological Chemistry

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Edited by Joseph M. JezSulfur is present in the amino acids cysteine and methionine and in a large range of essential coenzymes and cofactors and is therefore essential for all organisms. It is also a constituent of sulfate esters in proteins, carbohydrates, and numerous cellular metabolites. The sulfation and desulfation reactions modifying a variety of different substrates are commonly known as sulfation pathways. Although relatively little is known about the function of most sulfated metabolites, the synthesis of activated sulfate used in sulfation pathways is essential in both animal and plant kingdoms. In humans, mutations in the genes encoding the sulfation pathway enzymes underlie a number of developmental aberrations, and in flies and worms, their loss-of-function is fatal. In plants, a lower capacity for synthesizing activated sulfate for sulfation reactions results in dwarfism, and a complete loss of activated sulfate synthesis is also lethal. Here, we review the similarities and differences in sulfation pathways and associated processes in animals and plants, and we point out how they diverge from bacteria and yeast. We highlight the open questions concerning localization, regulation, and importance of sulfation pathways in both kingdoms and the ways in which findings from these "red" and "green" experimental systems may help reciprocally address questions specific to each of the systems.Sulfur (S) is an essential nutrient for all life forms. It is present in a plethora of metabolites of primary and secondary metabolism, most prominently in the amino acids cysteine and methionine, and cofactors such as iron-sulfur clusters, lipoic acid, and CoA. In the majority of these metabolites, sulfur is present in its reduced form of organic thiols; however, some compounds contain S in its oxidized form of sulfate (1, 2). Sulfate is transferred to suitable substrates onto hydroxyl or amino groups by sulfotransferases (3,4). These biological sulfation reactions as well as desulfation catalyzed by sulfatases are often denoted as sulfation pathways (Fig. 1) (5, 6).The activated sulfate for the sulfation pathways, 3Ј-phosphoadenosine 5-phosphosulfate (PAPS), 3 is formed from sulfate by two ATP-dependent steps: adenylation, i.e. the transfer of the AMP moiety of ATP to sulfate to form adenosine 5Ј-phosphosulfate (APS) by ATP sulfurylase (ATPS), and the phosphorylation of APS at its 3Ј-OH group by APS kinase. The two enzymes are either fused into a single enzyme PAPS synthase (PAPSS) in the animal kingdom or occur as independent proteins in the green lineage (7). The by-product of PAPS-dependent sulfation reactions, 3Ј-phosphoadenosine 5-phosphate (PAP), is finally dephosphorylated to AMP by 3Ј-nucleotidases. This reaction to remove PAP is important beyond the sulfation pathways, as PAP accumulation has many additional physiological effects (8,9). Sulfate activation to APS or PAPS is a prerequisite not only for sulfation pathways but also for primary sulfate assimilation in plants, algae, bacteria, and fungi (2). Parti...

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Enzyme Kinetics of PAPS-Sulfotransferase

James

2021

Methods in Molecular Biology

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SULFATION PATHWAYS: Insights into steroid sulfation and desulfation pathways

Cited by 41 publications

References 125 publications

The vitamin D metabolome: An update on analysis and function

The vitamin D metabolome: An update on analysis and function

Sulfation pathways from red to green

Enzyme Kinetics of PAPS-Sulfotransferase

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