Recombinant human SULT1A1 sulfates T4, T3, rT3 and 3,3'-T2 with the preference 3,3'-T2 >> rT3 > T3 > T4, and has the lowest Km of the human SULTs tested for both the iodothyronine (0.14 uM for 3,3'-T2 vs 33 uM for SULT1A3) and for PAPS (0.65 uM vs 2.7 uM).

Sulfation channels thyroid hormone toward degradation by the type I iodothyronine deiodinase, so iodothyronine sulfotransferase activity is an inactivating step in thyroid hormone metabolism.

The authors leave open whether SULT1A1 is the physiologically dominant iodothyronine sulfotransferase in human liver and kidney, despite its superior in vitro affinity.

An independent laboratory reproduces the SULT1A1 iodothyronine substrate preference reported by PMID:10199779, and extends the series: 3,5-T2 is by far the poorest acceptor. Since 3,5-T2 carries both of its iodines on the inner tyrosyl ring and is the only member of the series with an un-iodinated outer ring, the ordering identifies outer-ring iodine substitution adjacent to the 4'-hydroxyl - not the presence of that hydroxyl, which every iodothyronine has - as what SULT1A1 selects for.

Both common allozymes (SULT1A1*1 Arg213 and SULT1A1*2 His213) sulfate iodothyronines with the same substrate preference and similar Km; the Arg213His polymorphism changes catalytic activity and thermostability, not specificity.

SULT1A1 activity is present in native human thyroid tissue across 86 surgically obtained glands (35 normal, 26 nodular goiter, 25 autoimmune thyroid disease), establishing thyroid as a site of SULT1A1 expression and moving iodothyronine sulfation beyond recombinant-enzyme evidence.

Of the iodothyronines tested, only 3,3'-T2 was sulfated by native thyroid SULT activity, matching the substrate preference measured for recombinant SULT1A1 and supporting an intrathyroidal role in degrading 3,3'-T2 for iodide reutilization.

Hydroxylated PCB metabolites inhibit 3,3'-T2 sulfation by human SULT1A1 but not by human SULT1A3, discriminating the two closest paralogs on iodothyronine chemistry. The human enzymes here are recombinant (expressed in V79 cells); the liver cytosols assayed in the same study are rat, so this speaks to isozyme discrimination rather than to which enzyme carries the activity in human liver.

Equal IC50 values with T2 and T3 as substrate argue that 3,3'-T2 is the preferred iodothyronine acceptor of the sulfotransferases acting on thyroid hormone, independently corroborating the kinetic preference order.

Review placing sulfation alongside deiodination, glucuronidation and ether-link cleavage as one of the four classical routes of thyroid hormone metabolism, which is the pathway-level context for the proposed iodothyronine sulfotransferase activity term.

The first crystal structure of human SULT1A1 with a xenobiotic acceptor bound shows two p-nitrophenol molecules in the active site, explaining the enzyme's characteristic substrate inhibition, and reveals a flexible site that adapts to hydrophobic acceptors of varying size and shape.

SULT1A1 is characterized as a major human sulfotransferase that both detoxifies and bioactivates diverse promutagens and procarcinogens.

SULT1A1 co-crystallized with PAP and estradiol has a single E2 molecule bound in a non-productive orientation, a dead-end complex that quantitatively explains the partial substrate inhibition seen at high estradiol concentrations.

Kynurenic acid inhibits recombinant human SULT1A1 without being sulfated itself, so the assays measure genuine SULT1A1 sulfotransferase activity toward its own acceptors.

SULT1A1 (with SULT1A2) is the most efficient human sulfotransferase for the dietary flavanone hesperetin, forming preferentially the 3'-O-sulfate; hesperetin is conjugated at positions 7 and 3'.

Cytosolic sulfotransferases were used as model enzymes for ancestral-library directed evolution, and an evolved SULT variant was characterized structurally and kinetically, showing how few active-site mutations reshape substrate specificity.

Five crystal structures of SULT1A1 with PAP and different acceptors show a catalytically competent 2-naphthol complex (acceptor hydroxyl 2.34 A from His108), and demonstrate that active-site plasticity - notably a large movement of Phe247 - both enables broad specificity and opens a conserved second, non-productive acceptor site that causes substrate inhibition.

SULT1A1's substrate preference is for small phenolic compounds, in contrast to SULT1E1 whose preference is for estrogen acceptors.

Four of the eleven human SULTs assayed - SULT1A1, SULT1A2, SULT1A3 and SULT1C4 - sulfate ethanol; ethyl sulfate is described by the authors as a minor direct ethanol metabolite of interest chiefly as a consumption biomarker, and the highest ethanol-sulfating activity among human tissues was in small intestine.

Crystal structures of SULT1A2 and the SULT1A1*3 allozyme bound to PAP reveal a plastic substrate-binding pocket with two channels and identify Phe247 as a switch-like substrate-selectivity residue, giving a structural basis for substrate inhibition. Tyr149Phe mutagenesis of SULT1A2 raised Km ~40-fold.

SULT4A1 co-immunoprecipitates with SULT1A1 and SULT1A3 in human cells, and the interaction requires the conserved C-terminal dimerization motif of the sulfotransferases; SULT4A1 lowers SULT1A1/1A3 protein levels in neuronal cells, suggesting a chaperone-like regulatory role.

4-ethylphenol produced by gut bacteria from dietary tyrosine is sulfated to 4-EPS by SULT1A1 and other sulfotransferases in vitro; 4-EPS enters the brain, impairs oligodendrocyte maturation and myelination, and produces anxiety-like behaviour in mice. The tissue site of 4-EP sulfation in vivo is explicitly unresolved.

PAPS-dependent DNA binding of N-hydroxy-arylamine and N-hydroxy-heterocyclic-amine metabolites in human liver cytosol correlates with thermostable phenol sulfotransferase (SULT1A1) activity, and not with thermolabile PST or DHEA sulfotransferase; the correlation is confirmed by DCNP inhibition and thermostability profiling. Activity was detected in liver and colon cytosol but not in pancreas, larynx or bladder epithelium.

SULT1A3's selectivity for dopamine and other biogenic amines is conferred by a single acceptor-pocket residue, Glu146. The E146A substitution alone transforms SULT1A3's catalytic properties and substrate preference so that they resemble SULT1A1's. SULT1A1 carries Ala at the corresponding position.

HAST1 (SULT1A1) expressed in COS-7 cells sulfates 4-nitrophenol with Km 0.6 uM, whereas HAST3 (SULT1A3) prefers dopamine with Km 9.7 uM; each enzyme sulfates the other's preferred substrate with a Km at least two orders of magnitude worse. DCNP inhibition and thermostability profiles match liver cytosolic P-PST and M-PST respectively.

Determines the exon-intron structure, alternative noncoding first exons (IA and IB, which are alternative 5' UTRs rather than additional genes), promoter regions and chromosome 16 localization of the STP2 gene. STP2 is SULT1A2, not SULT1A1. STP2/SULT1A2 is the only gene newly characterized experimentally; STP1/SULT1A1, STM/SULT1A3, STE/SULT1E1 and rat phenol- and guinea-pig estrogen-sulfotransferase genes appear only as sequence or splice-junction comparisons.

The paper reports no new enzymology: no recombinant enzyme assays, no substrate-specificity experiments, no Km/Vmax or catalytic-rate measurements, no thermostability assays, and no functional comparison of the STP1 and STP2 proteins. Its enzymological content is background - that thermostable PST sulfonates relatively simple planar phenols and that its activity varies heritably between individuals - and the structural work is explicitly framed as enabling later investigation of how that activity is regulated.

SULT1A1 in dimeric form sulfonates paracetamol (acetaminophen); around 20-30% of a paracetamol dose is metabolized by hepatic sulfonation.

The generic phenol sulfate-conjugation reaction is assigned to the cytosol and to the aryl sulfotransferase activity of the SULT1A1 homodimer.

SULT1A1 sulfonates N-hydroxy-4-aminobiphenyl, a genotoxic metabolite of the industrial carcinogen 4-aminobiphenyl, in the liver.

SULT1A1 is one of several SULT dimers (1A1, 1A3, 1A4, 1C4, 1E1, 2A1) that sulfate acetaminophen; 30-44% of a therapeutic dose is converted to inactive sulfate conjugates.