Phytol, SSADH inhibitory diterpenoid of Lactuca sativa.
The succinic semialdehyde dehydrogenase (SSADH) inhibitory component was isolated from the EtOAc fraction of Lactuca sativa through repeated column chromatography; then, it was identified as phytol, a diterpenoid, based on the interpretation of several spectral data. Incubation of SSADH with the phytol results in a time-dependent loss of enzymatic activity, suggesting that enzyme modification is irreversible. The inactivation followed pseudo-first-order kinetics with the second-rate order constant of 6.15 x 10(-2) mM(-1) min(-1). Complete protection from inactivation was afforded by the coenzyme NAD+, whereas substrate succinic semialdehyde failed to prevent the inactivation of the enzyme; therefore, it seems likely that phytol covalently binds at or near the active site of the enzyme. It is postulated that the phytol is able to elevate the neurotransmitter GABA levels in central nervous system through its inhibitory action on one of the GABA degradative enzymes, SSADH.
Bang
Myun-Ho
MH
Graduate School of Biotechnology & Plant Metabolism Research Center, Kyunghee University, Suwon, Korea.
Choi
Soo Young
SY
Jang
Tae-O
TO
Kim
Sang Kook
SK
Kwon
Oh-Shin
OS
Kang
Tae-Cheon
TC
Won
Moo Ho
MH
Park
Jinseu
J
Baek
Nam-In
NI
D000445:Aldehyde Oxidoreductases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D002417:Cattle; D004224:Diterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D018545:Lactuca / Q000201:enzymology*; D010836:Phytol / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D035261:Plant Components, Aerial / Q000737:chemistry; D010936:Plant Extracts / Q000737:chemistry; D050644:Succinate-Semialdehyde Dehydrogenase
D004224:Diterpenes; D004791:Enzyme Inhibitors; D010936:Plant Extracts; D010836:Phytol; D000445:Aldehyde Oxidoreductases; D050644:Succinate-Semialdehyde Dehydrogenase