F. Papes et al., Lysine degradation through the saccharopine pathway in mammals: involvement of both bifunctional and monofunctional lysine-degrading enzymes in mouse, BIOCHEM J, 344, 1999, pp. 555-563
Lysine-oxoglutarate reductase and saccharopine dehydrogenase are enzymic ac
tivities that catalyse the first two steps of lysine degradation through th
e saccharopine pathway in upper eukaryotes. This paper describes the isolat
ion and characterization of a cDNA clone encoding a bifunctional enzyme bea
ring domains corresponding to these two enzymic activities. We partly purif
ied those activities from mouse liver and showed for the first time that bo
th a bifunctional lysine-oxoglutarate reductase/saccharopine dehydrogenase
and a monofunctional saccharopine dehydrogenase are likely to be present in
this organ. Northern analyses indicate the existence of two mRNA species i
n liver and kidney. The longest molecule, 3.4 kb in size, corresponds to th
e isolated cDNA and encodes the bifunctional enzyme. The 2.4 kb short trans
cript probably codes for the monofunctional dehydrogenase. Sequence analyse
s show that the bifunctional enzyme is likely to be a mitochondrial protein
. Furthermore, enzymic and expression analyses suggest that lysine-oxogluta
rate reductase/saccharopine dehydrogenase levels increase in livers of mice
under starvation. Lysine-injected mice also show an increase in lysine-oxo
glutarate reductase and saccharopine dehydrogenase levels.