Is rat LRRP Ba1-651 a Delta-1-pyrroline-5-carboxylate dehydrogenase activated by changes in the concentration of sweet molecules?
The liver is one of the most complex organs in the body, which responds to hepatocellular damage with inflammatory, regenerative and repair processes designed to restore functional liver tissue mass. Rat LRRP Ba1-651, a liver regeneration related protein induced during partial hepatectomy, is classified as a member of the aldehyde dehydrogenase (ALDh) 4A1 superfamily. During a BLAST protein search, this protein basically showed three structural and functional domains: an intermediate filament-like protein, a Delta-1-pyrroline-5-carboxylate dehydrogenase (P5CDh) and an atrial natriuretic factor (ANF) receptor. We suggest that all amniotic mammals possess a Ba1-651 ortholog to that of rats. The ANF receptor domain of rat LRRP Ba1-651, which domain is part of the receptor family ligand binding region, shows a very high sequence homology (almost identity) to the extracellular amino-terminal domains of the mammalian sweet taste receptor T1R2. This receptor belongs to the type C family of G protein coupled receptors (GPCRs) and is characterized by the presence of large extracellular amino-terminal domains, a nine cysteine domain of family 3 GPCR and a 7tm_3 transmembrane type domain. We suggest that rat LRRP Ba1-651 protein is a liver P5CDh-ANF that is activated by changes in the concentration of sweet molecules. If the sugar concentration in the organ increases due to liver damage or the intake of carbohydrate-rich or protein-rich foods, the P5CDh-ANF enzyme is activated to help in P5C catabolism. The hormone insulin probably plays a key role in the regulation of this enzyme. In the model that we propose, the P5CDh-ANF enzyme is activated by a conformational change in protein structure in the P5C docking site due to sugars binding in the AFN receptor region of the LRRP Ba1-651 protein. Our research could be a further understanding of the biological significance of this P5CDh-ANF enzyme, with important potential applications in the treatment of HPII and liver diseases and in liver transplantation. Further studies of our P5CDh-ANF enzyme are needed to clarify its features and functions, and which substances are involved in its induction. These might use liver cell lines or purified LRRP Ba1-651 protein with sweet molecules in vitro. Other experiments may help to localize LRRP Bal-651 in the organ and to link its abnormal presence or absence to certain tumors like hepatocellular carcinoma.
Tizzano
Marco
M
Department of Morphological-Biomedical Sciences, Section of Anatomy and Histology, University of Verona, Verona, Italy. taitiz1@hotmail.com <taitiz1@hotmail.com>
Sbarbati
Andrea
A
D050842:1-Pyrroline-5-Carboxylate Dehydrogenase / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D019281:Dimerization; D004926:Escherichia coli / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D008954:Models, Biological; D017434:Protein Structure, Tertiary; D051381:Rats; D043562:Receptors, G-Protein-Coupled; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D013045:Species Specificity; D013649:Taste; D013650:Taste Buds / Q000378:metabolism
D043562:Receptors, G-Protein-Coupled; C431926:taste receptors, type 1; D050842:1-Pyrroline-5-Carboxylate Dehydrogenase