ABSTRACT
Amyloidosis is a diverse entity that poses both diagnostic and treatment challenges. Whether systemic or local, amyloidosis has varied manifestations including occasional hepatic involvement. Hepatic amyloidosis, although rare, should be on the differential for those with unexplained hepatomegaly, cholestasis, alkaline phosphatase elevations, other associated organomegaly, and those with certain epidemiologic risks. In this study, we report a case of a man with systemic amyloid light chain amyloidosis with multiorgan involvement, acute liver injury, cholestasis, nephrotic syndrome, cardiomegaly, and bleeding diathesis.
ABSTRACT
NAD(+) is an essential coenzyme for hydride transfer enzymes and a substrate of sirtuins and other NAD(+)-consuming enzymes. Nicotinamide riboside is a recently discovered eukaryotic NAD(+) precursor converted to NAD(+) via the nicotinamide riboside kinase pathway and by nucleosidase activity and nicotinamide salvage. Nicotinamide riboside supplementation of yeast extends replicative life span on high glucose medium. The molecular basis for nicotinamide riboside uptake was unknown in any eukaryote. Here, we show that deletion of a single gene, YOR071C, abrogates nicotinamide riboside uptake without altering nicotinic acid or nicotinamide import. The gene, which is negatively regulated by Sum1, Hst1, and Rfm1, fully restores nicotinamide riboside import and utilization when resupplied to mutant yeast cells. The encoded polypeptide, Nrt1, is a predicted deca-spanning membrane protein related to the thiamine transporter, which functions as a pH-dependent facilitator with a K(m) for nicotinamide riboside of 22 microm. Nrt1-related molecules are conserved in particular fungi, suggesting a similar basis for nicotinamide riboside uptake.
