Sodium-coupled and electrogenic transport of B-complex vitamin nicotinic acid by slc5a8, a member of the Na/glucose co-transporter gene family

Elangovan Gopal, You Jun Fei, Seiji Miyauchi, Lina Zhuang, Puttur D Prasad, Vadivel Ganapathy

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

SMCT (sodium-coupled monocarboxylate transporter; slc5a8) is a Na +-coupled transporter for lactate, pyruvate and short-chain fatty acids. Similar to these already known substrates of SMCT, the water-soluble B-complex vitamin nicotinic acid also exists as a monocarboxylate anion (nicotinate) under physiological conditions. Therefore we evaluated the ability of SMCT to mediate the uptake of nicotinate. In mammalian cells, the cloned mouse SMCT (slc5a8) induced the uptake of nicotinate. The SMCT-induced uptake was Na+-dependent. The Michaelis constant for the uptake process was 296 ± 88 μM. The Na+-activation kinetics indicated that at least two Na+ ions are involved in the process. Among the various structural analogues tested, nicotinate was the most effective substrate. Nicotinamide and methylnicotinate were not recognized by the transporter. 2-Pyrazine carboxylate and isonicotinate interacted with the transporter to a moderate extent. SMCT-mediated uptake of nicotinate was inhibited by lactate and pyruvate. In the Xenopus laevis oocyte expression system, SMCT-mediated nicotinate transport was electrogenic, as evident from the nicotinate-induced inward currents under voltage-clamp conditions. Substrate-induced currents in this expression system corroborated the substrate specificity determined in the mammalian cell expression system. The kinetic parameters with regard to the affinity of the transporter for nicotinate and the Hill coefficient for Na + activation, determined by using the oocyte expression system, were also similar to those obtained from the mammalian cell expression system. We conclude that SMCT functions not only as a Na+-coupled transporter for short-chain fatty acids and lactate but also as a Na+-coupled transporter for the water-soluble vitamin nicotinic acid.

Original languageEnglish (US)
Pages (from-to)309-316
Number of pages8
JournalBiochemical Journal
Volume388
Issue number1
DOIs
StatePublished - May 15 2005

Fingerprint

Symporters
Vitamin B Complex
Facilitative Glucose Transport Proteins
Niacin
Genes
Sodium
Glucose
Volatile Fatty Acids
Cells
Induced currents
Substrates
Pyruvic Acid
Oocytes
Lactic Acid
Monocarboxylic Acid Transporters
Chemical activation
Niacinamide
Water
Clamping devices
Xenopus laevis

Keywords

  • Electrogenicity
  • Monocarboxylate transport
  • Nicotinate transport
  • Slc5a8
  • Sodium dependence
  • Sodium-coupled monocarboxylate transporter (SMCT)

ASJC Scopus subject areas

  • Biochemistry

Cite this

Sodium-coupled and electrogenic transport of B-complex vitamin nicotinic acid by slc5a8, a member of the Na/glucose co-transporter gene family. / Gopal, Elangovan; Fei, You Jun; Miyauchi, Seiji; Zhuang, Lina; Prasad, Puttur D; Ganapathy, Vadivel.

In: Biochemical Journal, Vol. 388, No. 1, 15.05.2005, p. 309-316.

Research output: Contribution to journalArticle

Gopal, Elangovan ; Fei, You Jun ; Miyauchi, Seiji ; Zhuang, Lina ; Prasad, Puttur D ; Ganapathy, Vadivel. / Sodium-coupled and electrogenic transport of B-complex vitamin nicotinic acid by slc5a8, a member of the Na/glucose co-transporter gene family. In: Biochemical Journal. 2005 ; Vol. 388, No. 1. pp. 309-316.
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AU - Fei, You Jun

AU - Miyauchi, Seiji

AU - Zhuang, Lina

AU - Prasad, Puttur D

AU - Ganapathy, Vadivel

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AB - SMCT (sodium-coupled monocarboxylate transporter; slc5a8) is a Na +-coupled transporter for lactate, pyruvate and short-chain fatty acids. Similar to these already known substrates of SMCT, the water-soluble B-complex vitamin nicotinic acid also exists as a monocarboxylate anion (nicotinate) under physiological conditions. Therefore we evaluated the ability of SMCT to mediate the uptake of nicotinate. In mammalian cells, the cloned mouse SMCT (slc5a8) induced the uptake of nicotinate. The SMCT-induced uptake was Na+-dependent. The Michaelis constant for the uptake process was 296 ± 88 μM. The Na+-activation kinetics indicated that at least two Na+ ions are involved in the process. Among the various structural analogues tested, nicotinate was the most effective substrate. Nicotinamide and methylnicotinate were not recognized by the transporter. 2-Pyrazine carboxylate and isonicotinate interacted with the transporter to a moderate extent. SMCT-mediated uptake of nicotinate was inhibited by lactate and pyruvate. In the Xenopus laevis oocyte expression system, SMCT-mediated nicotinate transport was electrogenic, as evident from the nicotinate-induced inward currents under voltage-clamp conditions. Substrate-induced currents in this expression system corroborated the substrate specificity determined in the mammalian cell expression system. The kinetic parameters with regard to the affinity of the transporter for nicotinate and the Hill coefficient for Na + activation, determined by using the oocyte expression system, were also similar to those obtained from the mammalian cell expression system. We conclude that SMCT functions not only as a Na+-coupled transporter for short-chain fatty acids and lactate but also as a Na+-coupled transporter for the water-soluble vitamin nicotinic acid.

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