The hepato-muscular metabolic axis and gluconeogenesis

During starvation alanine synthesised de novo by muscle is an important precursor for hepatic gluconeogenesis. The alanine carbon derives in part from branched-chain amino acids such as valine. In vitro incubations of muscle with [1-14 C]- or [U14C]-valine have shown that sufficient valine carbon passes beyond decarboxylation by branched-chain dehydrogenase, but escapes total oxidation, to account for the observed rate of de novo alanine synthesis. Experiments using hydroxymalonate (an inhibitor of malic enzyme) and mercaptopicolinate (an inhibitor of PEP carboxykinase) have shown that muscle alanine synthesis occurs via the latter route. Ketone bodies suppress muscle alanine formation suggesting a role in the conservation of glucogenic precursors in long-term starvation. Conversely alanine diminishes ketogenesis by isolated hepatocytes. It appears that there is an hepato-muscular metabolic axis operating by which liver and muscle metabolism is co-ordinately controlled by alanine and ketone bodies.