The cDNA coding for a rabbit renal Na+/dicarboxylate cotransporter, designated NaDC-1, was isolated by functional expression in Xenopus oocytes. NaDC-1 is approximately 2.3 kilobases length and codes protein of 593 amino acids. contains eight putative transmembrane domains, the sequence secondary structure are related to Na+/sulfate transporter, NaSi-1. Northern analysis shows that message abundant kidney small intestine, transporters may be found liver, lung, adrenal. transport succinate...

Complementary DNAs encoding seven different proteins related to the rabbit intestinal Na+/glucose cotransporter, SGLT1, were isolated from a renal cDNA library at relatively high stringency. The messages for RK-B RK-F single mRNA species 2.3 kilobases (kb) in heart and kidney. message RK-A was 4 kb found brain, lung, intestine, liver, RK-I approximately 3 all tissues tested. most abundant clone, RK-C, constituted nucleotides 66-2150 of sodium-nucleoside SNST1. 672-amino acid protein encoded...

We have used low-stringency screening with the human intestinal Na(+)-glucose cotransporter SGLT1 to isolate a 2,271-nucleotide cDNA (Hu14) from kidney. This clone, which encodes 672-residue protein, is 59% identical at amino acid level and has similar number arrangement of predicted membrane-spanning regions. It also shares significant sequence identity other Na(+)-coupled transporters. Northern blot analysis suggests strong expression Hu14 in kidney, but, unlike SGLT1, no intestine. been...

Mutations in the SLC13A5 gene that codes for Na+/citrate cotransporter, NaCT, are associated with early onset epilepsy, developmental delay and tooth dysplasia children. In this study, we identify additional mutations nine epilepsy patients from six families. To better characterize syndrome, families affected children answered questions about scope of illness treatment strategies. Currently, there no effective treatments, but some antiepileptic drugs targeting γ-aminobutyric acid system...

We have cloned a Na⁺-dependent, high affinity dicarboxylate transporter (NaDC3) from rat placenta. NaDC3 exhibits 48% identity in amino acid sequence with NaDC1, low transporter. NaDC3-specific mRNA is detectable kidney, brain, liver, and When expressed mammalian cells, mediates Na⁺-dependent transport of succinate a<i>K</i> _t 2 μm. The function shows sigmoidal relationship regard to Na⁺concentration, Hill coefficient 2.7. accepts number...

Sodium-dependent glucose transport occurs in the intestine and kidney of most animal species. The cDNA encoding Na+/glucose cotransporter from rabbit jejunum was used to examine distribution homologous mRNA other tissues intestines Northern blots extracted various were probed with radiolabeled cloned transporter. probe hybridized approximately 2.2 kb jejunum, renal cortex, medulla, indicating that related same size is found these tissues. With use probe, a 1.6-kb partial-length clone 484...

The renal Na(+)-dicarboxylate cotransporter reabsorbs Krebs cycle intermediates, such as succinate and citrate, from the glomerular filtrate. present study describes cloning characterization of human cotransporter, hNaDC-1. amino acid sequence hNaDC-1 is 78% identical to rabbit NaDC-1, 42% rat Na(+)-sulfate transporter, NaSi-1. carboxy terminus protein contains two N-glycosylation sites that appear be utilized. Xenopus oocytes injected with cRNA expressed a low-affinity Na(+)-dependent...

The kidney contains two Na⁺/glucose cotransporters, called SGLT2 and SGLT1, arranged in series along the length of proximal tubule. low-affinity transporter, SGLT2, is responsible for reabsorption most glucose kidney. There recent interest as a target treatment type II diabetes using selective inhibitors based on structure phenylglucoside, phlorizin (phloretin-2′-β-glucoside). In this study, we examined inhibition α-methyl-d-glucopyranose transport by new candidate drug,...

Abstract The effects of estradiol, testosterone, and pituitary extract on hepatic microsomal enzymes were studied in sham‐operated gonadectomized immature brook trout. Estradiol reduced the specific content cytochromes P‐450 b 5 by 70% or more both groups. Testosterone also decreased levels total , but to a lesser extent. These latter not evident when contents normalized per g liver. Immunoblot analysis with antibodies forms from teleost (scup) showed presence cross‐reacting proteins control...

Neurons contain a high-affinity Na + /dicarboxylate cotransporter for absorption of neurotransmitter precursor substrates, such as α-ketoglutarate and malate, which are subsequently metabolized to replenish pools neurotransmitters, including glutamate. We have isolated the cDNA coding from mouse brain, called mNaDC-3. The mRNA mNaDC-3 is found in brain choroid plexus well kidney liver. transporter has broad substrate specificity dicarboxylates, succinate, α-ketoglutarate, fumarate,...

The two-electrode voltage clamp was used to study the currents associated with transport of succinate by cloned Na⁺/dicarboxylate cotransporter, NaDC-1, expressed in<i>Xenopus</i> oocytes. presence induced inward which were dependent on concentrations and sodium, membrane potential. At −50 mV, the<i>K</i> _0.5^succinate 180 μm <i>K</i> _0.5^Na+ 19 mm. Hill coefficient 2.3, is consistent a stoichiometry 3 Na⁺:1 divalent anion...

Polyclonal antibodies were prepared against the rabbit renal Na(+)-dicarboxylate cotransporter, NaDC-1. The raised in chickens a fusion protein consisting of 60-amino acid peptide from NaDC-1 and glutathione S-transferase. These specifically recognized Western blots could immunoprecipitate full-length after vitro translation. antifusion 63 kDa brush-border membrane vesicles (BBMV), similar to predicted mass 66 kDa. Two proteins 57 115 intestinal membranes. A was Xenopus oocytes injected with...

In mammals, citric acid cycle intermediates play a key role in regulating various metabolic processes, such as fatty synthesis and glycolysis. Members of the sodium-dependent SLC13 transporter family mediate transport di- tricarboxylates into cells. members have been implicated lifespan extension resistance to high-fat diets; thus, they are emerging drug targets for aging disorders. We previously characterized structural determinants substrate cation binding human NaDC3/SLC13A3 using...

This study investigated the ability of renal Na(+)-dicarboxylate cotransporter, NaDC-1, to transport water. Rabbit NaDC-1 was expressed in Xenopus laevis oocytes, cotransporter activity measured as inward current generated by substrate (citrate or succinate), and water monitored changes oocyte volume. In absence substrates, oocytes expressing showed an increase osmotic permeability, which directly correlated with expression level NaDC-1. When transporting there a concomitant solute-coupled...

Metabolic intermediates, such as succinate and citrate, regulate important processes ranging from energy metabolism to fatty acid synthesis. Cytosolic concentrations of these metabolites are controlled, in part, by members the SLC13 gene family. The molecular mechanism underlying Na(+)-coupled di- tricarboxylate transport this family is understood poorly. human Na(+)/dicarboxylate cotransporter NaDC3 (SLC13A3) found various tissues, including kidney, liver, brain. In addition citric cycle...

The Na⁺/citrate transporter, NaCT (SLC13A5), is a therapeutic target for metabolic diseases. Citrate an important signaling molecule that regulates the activity of lipid- and glucose-metabolizing enzymes in cells. Previous studies identified two compounds, PF-06649298 (compound <b>2</b>) PF-06678419 <b>4</b>), inhibit human with high affinity, one compounds demonstrated specificity relative to other SLC13 family members. Here we use molecular modeling site-directed mutagenesis...