Taurine
(2-aminoethanesulfonic acid) is a sulfur-containing organic acid, which
has various physiological functions, including membrane stabilization,
cell-volume regulation, mitochondrial protein translocation,
anti-oxidative activity, neuroprotection against neurotoxicity and
modulation of intracellular calcium levels. Taurine also activates GABAA receptors and glycine receptors. Mammalian fetuses and infants are dependent on taurine delivered from their mothers via either the placenta or their mother's milk.Taurine is a molecule that links mother-fetus or mother-infant bonding.This review describes the functions of taurine and the mechanisms of action of taurine in fetal and brain development. Taurine
is involved in regulating the proliferation of neural progenitors,
migration of newly-generated neurons, and the synapse formation of
neurons after migration during fetal and neonatal development. In this
review, we also discuss the environmental factors that might influence
the functional roles of taurine in neural development.
Nutrient sulfate
has numerous roles in mammalian physiology and is essential for healthy
fetal growth and development. The fetus has limited capacity to
generate sulfate and relies on sulfate supplied from the maternal circulation via placentalsulfate transporters. The placenta also has a high sulfate requirement for numerous molecular and cellular functions, including sulfate
conjugation (sulfonation) to estrogen and thyroid hormone which leads
to their inactivation. Accordingly, the ratio of sulfonated (inactive)
to unconjugated (active) hormones modulates endocrine function in fetal,
placental and
maternal tissues. During pregnancy, there is a marked increase in the
expression of genes involved in transport and generation of sulfate in the mouse placenta, in line with increasing fetal and placental demands for sulfate. The maternal circulation also provides a vital reservoir of sulfate for the placenta and fetus, with maternal circulating sulfate
levels increasing by 2-fold from mid-gestation. However, despite
evidence from animal studies showing the requirement of maternal sulfate supply for placental and fetal physiology, there are no routine clinical measurements of sulfate or consideration of dietary sulfate
intake in pregnant women. This is also relevant to certain xenobiotics
or pharmacological drugs which when taken by the mother use significant
quantities of circulating sulfate for detoxification and clearance, and thereby have the potential to decrease sulfonation capacity in the placenta and fetus. This article will review the physiological adaptations of the placenta for maintaining sulfate homeostasis in the fetus and placenta, with a focus on pathophysiological outcomes in animal models of disturbed sulfate homeostasis.
The protein encoded by this gene is an apical membrane
Na(+)-sulfate cotransporter involved in sulfate homeostasis in the
kidney. Defects in this gene lead to many pathophysiologic problems.
[provided by RefSeq, May 2016]
Expression
Biased expression in kidney (RPKM 26.2), small intestine (RPKM 5.7) and 1 other tissue See more
The
SLC13 gene family consists of five members in humans, with
corresponding orthologs from different vertebrate species. All five
genes code for sodium-coupled transporters that are found on the plasma
membrane. Two of the transporters, NaS1 and NaS2, carry substrates such
as sulfate,selenate and thiosulfate. The other members of the family
(NaDC1, NaDC3, and NaCT) are transporters for di- and tri-carboxylates
including succinate, citrate and alpha-ketoglutarate. The SLC13
transporters from vertebrates are electrogenic and they produce inward
currents in the presence of sodium and substrate.
Substrate-independent
leak currents have also been described.
Structure-function studies have
identified the carboxy terminal half of these proteins as the most
important for determining function. Transmembrane helices 9 and 10 may
form part of the substrate permeation pathway and participate in
conformational changes during the transport cycle. This review also
discusses new members of the SLC13 superfamily that exhibit both
sodium-dependent and sodium-independent transport mechanisms. The Indy
protein from Drosophila, involved in determining lifespan, and the plant
vacuolar malate transporter are both sodium-independent dicarboxylate
transporters, possibly acting as exchangers. The purpose of this review
is to provide an update on new advances in this gene family,
particularly on structure-function studies and new members of the
family.
High endothelial
venules (HEV) are specialized postcapillary venules found in lymphoid
organs and chronically inflamed tissues that support high levels of
lymphocyte extravasation from the blood. One of the major
characteristics of HEV endothelial cells (HEVEC) is their capacity to
incorporate large amounts of sulfate into sialomucin-type
counter-receptors for thelymphocyte homing receptor L-selectin. Here,
we show that HEVEC express twofunctional classes of sulfate
transporters defined by their differential sensitivity to the
anion-exchanger inhibitor 4,4'-diisothiocyanostilbene-2, 2'-disulfonic
acid (DIDS), and we report the molecular characterization of a
DIDS-resistant sulfate transporter from human HEVEC, designated SUT-1.
SUT-1 belongs to the family of Na(+)-coupled anion transporters and
exhibits 40-50% amino acid identity with the rat renal Na(+)/sulfate
cotransporter, NaSi-1, as well as with the human and rat
Na(+)/dicarboxylate cotransporters, NaDC-1/SDCT1 and NaDC-3/SDCT2.
Functional expression studies in cRNA-injected Xenopus laevis oocytes
showed that SUT-1 mediates high levels of Na(+)-dependent sulfate
transport, which is resistant to DIDS inhibition. The SUT-1 gene mapped
to human chromosome 7q33. Northern blotting analysis revealed that SUT-1
exhibits a highly restricted tissue distribution, with abundant
expression in placenta. Reverse transcription-PCR analysis indicated
that SUT-1 and the diastrophic dysplasia sulfate transporter (DTD), one
of the two known human DIDS-sensitive sulfate transporters, are
coexpressed in HEVEC. SUT-1 and DTD could correspond, respectively, to
the DIDS-resistant and DIDS-sensitive components of sulfate uptake in
HEVEC. Together, these results demonstrate that SUT-1 is a distinct
human Na(+)-coupled sulfate transporter, likely to play a major role in
sulfate incorporation in HEV.
Human
placental sulfate transporter mRNA profiling from term pregnancies
identifies abundant SLC13A4 in syncytiotrophoblasts and SLC26A2 in
cytotrophoblasts. Simmons DG, et al. Placenta, 2013 Apr. PMID 23453247 Sulfate is an important nutrient for fetal growth and development. The
fetus has no mechanism for producing its own sulfate and is therefore
totally reliant on sulfate from the maternal circulation via placental
sulfate transport. To build a model of directional sulfate transport in
the placenta, we investigated the relative abundance of the 10 known
sulfate transporter mRNAs in human placenta from uncomplicated term
pregnancies. SLC13A4 and SLC26A2 were the most abundant sulfate
transporter mRNAs, which localized to syncytiotrophoblast and
cytotrophoblast cells, respectively. These findings indicate important
physiological roles for SLC13A4(NAS1) and SLC26A2(SUT1) in human placental sulfate
transport.
The protein encoded by this gene is a transmembrane
glycoprotein that transports chloride ions across the cell membrane in
exchange for bicarbonate ions. It is localized to the mucosa of the
lower intestinal tract, particularly to the apical membrane of columnar
epithelium and some goblet cells. The protein is essential for
intestinal chloride absorption, and mutations in this gene have been
associated with congenital chloride diarrhea. [provided by RefSeq, Oct
2008]
Expression
Biased expression in colon (RPKM 709.1), duodenum (RPKM 299.0) and 1 other tissue See more
STAS_SulP_like_sulfate_transporter; Sulphate Transporter and Anti-Sigma
factor antagonist domain of SulP-like sulfate transporters, plays a role
in the function and regulation of the transport activity, proposed
general NTP binding function
Protein 1..764
/product="chloride anion exchanger"
/note="down-regulated in adenoma protein; solute carrier
family 26 (anion exchanger), member 3"
/calculated_mol_wt=84374
Region 73..475
/region_name="Sulfate_transp"
/note="Sulfate permease family; pfam00916"
/db_xref="CDD:279284"
Region 376..432
/region_name="AtpE"
/note="FoF1-type ATP synthase, membrane subunit
c/Archaeal/vacuolar-type H+-ATPase, subunit K [Energy
production and conversion]; COG0636"
Region 526..712
/region_name="STAS_SulP_like_sulfate_transporter"
/note="Sulphate Transporter and Anti-Sigma factor
antagonist domain of SulP-like sulfate transporters, plays
a role in the function and regulation of the transport
activity, proposed general NTP binding function; cd07042"
GeneRIF: TNFalpha may act reciprocally with DRA, leading to the
development of intestinal inflammation.
Talletin vuonna 2002 artikkelin :Fernandes I et al. Sulfate homeostasis, NaSi-1 cotransporter, andSAT-1 exhancer expression in chronic renal failure in rats. Kidney Int 2001 Jan ; 59(1):210-21. Jouduin K-vitamiinityöni yhteydessä katsomaan rikkiaineenvaihduntaa, koska osa K-vitamiinifunktioista toimi sillä alueella ( sulfotransferaasien ja arylsulfataasien tarvitsemana cofaktorina ja lipidisynteesien alueella myös sulfatidien synteesin varhaisvaihe vaati Kvitamiinia kuten päätösvaihekien. samoin myös B6-vitamiini. Rikistä oli varsin vähän tietoa ravinto-opin kirjoissa ja kuitenkin sen osuus proteiineissa on yhtä konventionelli kuin typen niin että niillä on proteiinistruktuurissa tietty normaali suhteensa N:S. Tässä artikkelissa jonka säästin, mainittiin viime lauseessa, että "kroonisessa munuaisviassa hypersulfatemia aiemmin kuin hyperfosfatemia". Kirjoitin joskus paperin reunaan: "Katso tämä asia!".
Tänään etsin PubMed hakulaitella sanalla Hypersulfatemia ja saan 8 vastausta, joisa on juuri tämä artikkeli numero 2.
Katson näitä nyt.
The pharmacokinetics (PK) of an oral sulfate solution (OSS) for bowel
cleansing preparation was studied. OSS (30 g of sulfate) was split
between 2 doses, 12 hours apart. Safety measures included
electrocardiography, vital signs, adverse events, hematology, blood
chemistry, and urinalysis. Six adult patients with moderate renal
disease (MRD), 6 with mild-moderate hepatic disease (M/MHD), and 6
normal healthy volunteers (NHVs) completed the study. Adverse events
were mild to moderate in severity and were mainly limited to headache
and expected gastrointestinal symptoms. Serum sulfate levelswere highly
variable at all times, even after adjusting for baseline. Sulfate was
higher in MRD in comparison to the other groups. The C(max) and AUC were
higher in the patients, but no statistically significant differences
emerged.
Sulfate levels returned to predose values within 54 hours after
dosing. No electrolyte disturbances occurred. Urinary sulfate excretion
was approximately 20% of the dose. OSS was well tolerated. The types
and severity of adverse events were similar to those seen in large phase
III trials. While patients with MRD had elevated sulfate, the levels
were less than those in renal failure and did not alter biochemical
parameters that are associated with hypersulfatemia.
Fernandes I, Laouari D, Tutt P, Hampson G, Friedlander G, Silve C.
Kidney Int. 2001 Jan;59(1):210-21.
It is known that hypersulfatemia, like hyperphosphatemia, occurs in
chronic renal failure (CRF). The aim of this study was to assess the
effects of CRF on sulfate homeostasis and on sodium sulfate cotransport
(NaSi-1) and sulfate/oxalate-bicarbonate exchanger (Sat-1) expression in
the kidney. In addition, sulfate homeostasis was compared with
phosphate homeostasis...Free Article
Although inorganic sulfate is an essential and ubiquitous anion in human
biology, it is infrequently assayed in clinical chemistry today.
Serum
sulfate is difficult to measure accurately without resorting to
physicochemical methods, such as ion chromatography, although many other
techniques have been described.
It is strongly influenced by a variety
of physiological factors, including age, diet, pregnancy, and drug
ingestion.
Urinary excretion is the principal mechanism of disposal for
the excess sulfate produced by sulfur amino acid oxidation, and the
kidney is the primary site of regulation.
In renal failure, sulfoesters
accumulate and hypersulfatemia contributes directly to the unmeasured anion gap characteristic of the
condition.
In contrast, sulfate in urine is readily assayed by a number
of means, particularly nephelometry after precipitation as a barium
salt.
Sulfate is most commonly assayed today as part of the clinical
workup for nephrolithiasis, because sulfate is a major contributor to
the ionic strength of urine and alters the equilibrium constants
governing saturation and precipitation of calcium salts.
Total sulfate
deficiency has hitherto not been described, although genetic defects in
sulfate transporters have been associated recently with congenital
osteochondrodystrophies that may be lethal.
New insights into sulfate
transport and its hormonal regulation may lead to new clinical
applications of sulfate analysis
Concentrations of sulfate can increaseeightfold in the blood of
patients with severe reductions in glomerular filtration rate. Sulfate
enters the body almost exclusively as the amino acids cysteine and
methionine, and leaves in the urine predominantly as inorganic sulfate.
Concentrations in plasma may exceed 2.5 mol/L in renal failure, and
raise the anion gap by 5 mEq/L.
In studies by the author and colleagues,
hemodialysis using large dialyzers and brisk blood flow rates
effectively lowered the concentrations of sulfate in plasma to normal in
the immediate post dialysis period; the sulfate reduction ratio
actually exceeded the urea reduction ratio.
Significant correlation was
observed between the two ratios.
Concentrations of sulfate, in
conjunction with other data, may prove useful for estimating dietary
intake of protein and monitoring control of acid-base balance.
Although hypermagnesemia purportedly lowers the anion gap (AG), we have
shown previously that increases in the serum concentration of the
unmeasured cation (UC) Mg due to therapeutic infusion of MgSO4 are not
associated with AG reduction. To assess our hypothesis that increases in
serum SO4 (unmeasured anion, UA) offset the effect of elevated serum Mg
on the AG, we prospectively studied 11 patients receiving MgSO4
intravenously for toxemia of pregnancy. After 6 h of MgSO4 infusion,
serum Mg increased by 2.1 +/- 0.2 (SE) mEq/l (p less than 0.001) without
a significant decrease in the AG. Concomitantly, serum SO4 increased by
1.4 +/- 0.2 mEq/l. Comparison of the renal handling of SO4 versus Mg
showed a higher fractional excretion of the former, probably accounting
in part for the smaller increment of serum SO4 than of Mg. Comparison of
the change in serum SO4 minus that of Mg indicated that, on the
average, 70% of the observed 1.0 +/- 0.7 mEq/l reduction in AG was
accounted for by the observed changes in the two pertinent unmeasured
ions. A small decrement in serum Ca probably was a quantitatively minor
factor tending to obviate a greater decrease in AG. We conclude that hypersulfatemia attenuates the reduction in AG that would otherwise accompany MgSO4-induced hypermagnesemia.
Serum sulfate concentrations may reach five to ten times normal in renal
failure patients dialyzed on a sorbent cartridge system, and these
patients have elevated alkaline phosphatase levels suggesting an
increased incidence of renal oseodystrophy. We studied the effect of
adding sulfate on ionized calcium (Ca2+) in human serum in vitro and in
rat serum in vivo. K2SO4 or Na2SO4:NaCl mixtures were added to aliquots
of serum from normal subjects to reproduce the observed biologic range
of sulfate concentrations up to 10 mmol. Serum Ca2+ concentration was
found to decrease linearly as serum sulfate concentration increased, for
each subject. The weighted mean slope estimates of the effect of
sulfate on ionized calcium in two experiments were -.0197 and -.0181.
Rats were infused through the inferior vena cava with 2 mL of either 200
mmol NaCl (N = 5) or 100 mmol Na2SO4 (N = 6), after ligation of the
renal arteries and veins and withdrawal of 2 mL blood for baseline
studies. The animals were killed by exsanguination from the aorta after a
five-minute equilibration period. In rats administered NaCl, no
difference in Ca2+ or sulfate concentration was found between pre- and
postinfusion sera. In the Na2SO4 treated rats, however, a significant
mean increase of 0.635 mmol (p less than .005) in serum sulfate
concentration was associated with a significant mean decrease of -0.062
mmol (p less than .01) in serum Ca2+ concentration. We conclude that the
acute in vitro and in vivo addition of sulfate results in a decrease in
serum Ca2+ concentration. Thus, hypersulfatemia,
which is present chronically in patients on sorbent dialysis systems,
may contribute to elevated alkaline phosphatase levels in these
patients.
