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Am J Physiol Regul Integr Comp Physiol 291: R936-R946, 2006. First published June 1, 2006; doi:10.1152/ajpregu.00162.2006
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APPETITE, OBESITY, DIGESTION, AND METABOLISM

Oxidative phosphorylation and its coupling to mitochondrial creatine and adenylate kinases in human gastric mucosa

Marju Gruno,1 Nadezhda Peet,1 Evelin Seppet,1 Lumme Kadaja,1 Kalju Paju,1 Margus Eimre,1 Ehte Orlova,1 Margot Peetsalu,1 Andres Tein,1 Jaan Soplepmann,1 Uwe Schlattner,2 Ants Peetsalu,1 and Enn K. Seppet1

1Department of Pathophysiology, Centre of Molecular and Clinical Medicine, Faculty of Medicine, Department of Surgery, University of Tartu, Tartu, Estonia; 2Institute of Cell Biology, ETH Zürich, Zürich, Switzerland

Submitted 8 March 2006 ; accepted in final form 17 May 2006

Energy metabolism in gastrobiopsy specimens of the antral and corpus mucosa, treated with saponin to permeabilize the cells, was studied in patients with gastric diseases. The results show twice lower oxidative capacity in the antral mucosa than in the corpus mucosa and the relative deficiency of antral mitochondria in complex I. The mucosal cells expressed mitochondrial and cytosolic isoforms of creatine kinase and adenylate kinase (AK). Creatine (20 mM) and AMP (2 mM) markedly stimulated mitochondrial respiration in the presence of submaximal ADP or ATP concentrations, and creatine reduced apparent Km for ADP in stimulation of respiration, which indicates the functional coupling of mitochondrial kinases to oxidative phosphorylation. Addition of exogenous cytochrome c increased ADP-dependent respiration, and the large-scale cytochrome c effect (≥20%) was associated with suppressed stimulation of respiration by creatine and AMP in the mucosal preparations. These results point to the impaired mitochondrial outer membrane, probably attributed to the pathogenic effects of Helicobacter pylori. Compared with the corpus mucosa, the antral mucosa exhibited greater sensitivity to such type of injury as the prevalence of the large-scale cytochrome c effect was twice higher among the latter specimens. Active chronic gastritis was associated with decreased respiratory capacity of the corpus mucosa but with its increase in the antral mucosa. In conclusion, human gastric mucosal cells express the mitochondrial and cytosolic isoforms of CK and AK participating in intracellular energy transfer systems. Gastric mucosa disease is associated with the altered functions of these systems and oxidative phosphorylation.

human stomach mucosa; corpus; antrum


Address for reprint requests and other correspondence: E. K. Seppet, Dept. of Pathophysiology, Faculty of Medicine, Univ. of Tartu, 19 Ravila St., 50411 Tartu, Estonia (e-mail: enn.seppet{at}ut.ee)






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