PMID- 18539591
OWN - NLM
STAT- MEDLINE
DCOM- 20080922
LR  - 20210206
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 283
IP  - 31
DP  - 2008 Aug 1
TI  - Nonenzymatic proton handling by carbonic anhydrase II during H+-lactate 
      cotransport via monocarboxylate transporter 1.
PG  - 21655-67
LID - 10.1074/jbc.M802134200 [doi]
AB  - Carbonic anhydrase (CA) is a ubiquitous enzyme catalyzing the equilibration of 
      carbon dioxide, protons, and bicarbonate. For several acid/base-coupled membrane 
      carriers it has been shown that the catalytic activity of CA supports transport 
      activity, an interaction coined "transport metabolon." We have reported that CA 
      isoform II (CAII) enhances lactate transport activity of the monocarboxylate 
      transporter isoform I (MCT1) expressed in Xenopus oocytes, which does not require 
      CAII catalytic activity (Becker, H. M., Fecher-Trost, C., Hirnet, D., Sultemeyer, 
      D., and Deitmer, J. W. (2005) J. Biol. Chem. 280, 39882-39889 ). Coexpression of 
      MCT1 with either wild type CAII or the catalytically inactive mutant CAII-V143Y 
      similarly enhanced MCT1 activity, although injection of CAI or coexpression of an 
      N-terminal mutant of CAII had no effect on MCT1 transport activity, demonstrating 
      a specific, nonenzymatic action of CAII on lactate transport via MCT1. If the 
      H(+) gradient was set to dominate the rate of lactate transport by applying low 
      concentrations of lactate at a high H(+) concentration, the effect of CAII was 
      largest. We tested the hypothesis of whether CAII helps to shuttle H(+) along the 
      inner face of the cell membrane by measuring the pH change with fluorescent dye 
      in different areas of interest during focal lactate application. Intracellular pH 
      shifts decayed from the focus of lactate application to more distant sites much 
      less when CAII had been injected. We present a hypothetical model in which the 
      effective movement of H(+) into the bulk cytosol is increased by CAII, thus 
      slowing the dissipation of the H(+) gradient across the cell membrane, which 
      drives MCT1 activity.
FAU - Becker, Holger M
AU  - Becker HM
AD  - Abteilung fur Allgemeine Zoologie, FB Biologie, Technische Universitat 
      Kaiserslautern, Kaiserslautern, Germany. h.becker@biologie.uni-ki.de
FAU - Deitmer, Joachim W
AU  - Deitmer JW
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080606
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Fluorescent Dyes)
RN  - 0 (Monocarboxylic Acid Transporters)
RN  - 0 (Protons)
RN  - 33X04XA5AT (Lactic Acid)
RN  - EC 4.2.1.- (Carbonic Anhydrase II)
RN  - EC 4.2.1.1 (Carbonic Anhydrases)
SB  - IM
MH  - Animals
MH  - Carbonic Anhydrase II/*chemistry
MH  - Carbonic Anhydrases/metabolism
MH  - Cell Membrane/metabolism
MH  - Fluorescent Dyes/pharmacology
MH  - Humans
MH  - Hydrogen-Ion Concentration
MH  - Lactic Acid/*chemistry
MH  - Models, Biological
MH  - Monocarboxylic Acid Transporters/*metabolism
MH  - Mutation
MH  - Oocytes/metabolism
MH  - Patch-Clamp Techniques
MH  - Protons
MH  - Xenopus
EDAT- 2008/06/10 09:00
MHDA- 2008/09/23 09:00
CRDT- 2008/06/10 09:00
PHST- 2008/06/10 09:00 [pubmed]
PHST- 2008/09/23 09:00 [medline]
PHST- 2008/06/10 09:00 [entrez]
AID - S0021-9258(19)54660-9 [pii]
AID - 10.1074/jbc.M802134200 [doi]
PST - ppublish
SO  - J Biol Chem. 2008 Aug 1;283(31):21655-67. doi: 10.1074/jbc.M802134200. Epub 2008 
      Jun 6.