Saccharopine (L-Saccharopine) hydrochloride, a lysine degradation intermediate, is a mitochondrial toxin. Lysine and α-ketoglutarate are converted into Saccharopine hydrochloride by the lysine-ketoglutarate reductase. Saccharopine hydrochloride is then oxidized to α-aminoapidate semialdehyde and glutamate by the saccharopine dehydrogenase. Saccharopine hydrochloride impairs development by disrupting mitochondrial homeostasis[1][2][3].
Saccharopine 积累导致线粒体损伤和功能丧失，这是由 C. elegans 中 α-氨基己二酸半醛合酶 (AASS-1) 的糖苷脱氢酶 (SDH) 突变引起的[1]。
Saccharopine 积累可导致 Aass 突变小鼠的线粒体损伤和进行性出生后生长迟缓[1]。
[1]. Zhou J, et, al. The lysine catabolite saccharopine impairs development by disrupting mitochondrial homeostasis. J Cell Biol. 2019 Feb 4;218(2):580-597.
[2]. Leandro J, et, al. Saccharopine, a lysine degradation intermediate, is a mitochondrial toxin. J Cell Biol. 2019 Feb 4;218(2):391-392.
[3]. Papes F, et, al. Lysine degradation through the saccharopine pathway in mammals: involvement of both bifunctional and monofunctional lysine-degrading enzymes in mouse. Biochem J. 1999 Dec 1;344 Pt 2(Pt 2):555-63.