Bioinformatic Study of Possible Acute Regulation of Acid Secretion in the Stomach.

The gastric H+,K+-ATPase is an integral membrane protein which derives energy from the hydrolysis of ATP to transport H+ ions from the parietal cells of the gastric mucosa into the stomach in exchange for K+ ions. It is responsible for the acidic environment of the stomach, which is essential for digestion. Acid secretion is regulated by the recruitment of the H+,K+-ATPase from intracellular stores into the plasma membrane on the ingestion of food. The similar amino acid sequences of the lysine-rich N-termini α-subunits of the H+,K+- and Na+,K+-ATPases, suggests similar acute regulation mechanisms, specifically, an electrostatic switch mechanism involving an interaction of the N-terminal tail with the surface of the surrounding membrane and a modulation of the interaction via regulatory phosphorylation by protein kinases. From a consideration of sequence alignment of the H+,K+-ATPase and an analysis of its coevolution with protein kinase C and kinases of the Src family, the evidence points towards a phosphorylation of tyrosine-7 of the N-terminus by either Lck or Yes in all vertebrates except cartilaginous fish. The results obtained will guide and focus future experimental research.

The Role of the Gastrointestinal Microbiome in Liver Disease.

Liver disease is a major global health problem leading to approximately two million deaths a year. This is the consequence of a number of aetiologies, including alcohol-related, metabolic-related, viral infection, cholestatic and immune disease, leading to fibrosis and, eventually, cirrhosis. No specific registered antifibrotic therapies exist to reverse liver injury, so current treatment aims at managing the underlying factors to mitigate the development of liver disease. There are bidirectional feedback loops between the liver and the rest of the gastrointestinal tract via the portal venous and biliary systems, which are mediated by microbial metabolites, specifically short-chain fatty acids (SCFAs) and secondary bile acids. The interaction between the liver and the gastrointestinal microbiome has the potential to provide a novel therapeutic modality to mitigate the progression of liver disease and its complications. This review will outline our understanding of hepatic fibrosis, liver disease, and its connection to the microbiome, which may identify potential therapeutic targets or strategies to mitigate liver disease.