PMID- 3379826
OWN - NLM
STAT- MEDLINE
DCOM- 19880718
LR  - 20190725
IS  - 0021-5198 (Print)
IS  - 0021-5198 (Linking)
VI  - 46
IP  - 2
DP  - 1988 Feb
TI  - In vitro effects of various heterocyclic thiol compounds and beta-lactam 
      antibiotics on vitamin K-dependent gamma-glutamylcarboxylation activity in liver 
      microsomes.
PG  - 165-72
AB  - The in vitro effect of N-methyltetrazolethiol (NMTT), one of the common 
      substituents at the 3'-position of the cephem in various beta-lactam antibiotics, 
      on liver microsomal gamma-glutamylcarboxylation (gamma-carboxylation) activity 
      was examined using solubilized rat liver enzyme. The enzyme activity was 
      inhibited by coexisting with NMTT and NADH, and this inhibitory activity could be 
      suppressed by the addition of a sulfhydryl compound such as dithiothreitol (DTT), 
      glutathione or cysteine. Various five-membered heterocyclic thiol compounds 
      exhibited concentration-dependent inhibition of microsomal gamma-carboxylation 
      activity. These inhibitory actions diminished markedly in the presence of 1 mM 
      DTT. In vitro gamma-carboxylation activity also decreases upon addition of 
      various beta-lactam antibiotics at 1 or 10 mM, depending upon the concentration 
      of the drug. Among the heterocyclic thiol compounds, there is a correlation 
      between their inhibitory activities and hydrophobicities. Thus, the in vitro 
      inhibitory activity of heterocyclic thiol compounds and beta-lactam antibiotics 
      on microsomal gamma-carboxylation activity is not correlated with their molecular 
      structures, but rather depends on their hydrophobicities and with the 
      concentrations in the reaction mixture.
FAU - Oka, T
AU  - Oka T
AD  - Kanzakigawa Laboratory, Shionogi Research Laboratories, Shionogi & Co., Ltd., 
      Osaka, Japan.
FAU - Touchi, A
AU  - Touchi A
FAU - Ezumi, K
AU  - Ezumi K
FAU - Yamakawa, M
AU  - Yamakawa M
FAU - Matsubara, T
AU  - Matsubara T
LA  - eng
PT  - Journal Article
PL  - Japan
TA  - Jpn J Pharmacol
JT  - Japanese journal of pharmacology
JID - 2983305R
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Heterocyclic Compounds)
RN  - 0 (Sulfhydryl Compounds)
RN  - 0 (Sulfhydryl Reagents)
RN  - 0 (beta-Lactams)
RN  - 12001-79-5 (Vitamin K)
RN  - EC 6.- (Ligases)
RN  - EC 6.4.- (Carbon-Carbon Ligases)
RN  - EC 6.4.- (glutamyl carboxylase)
SB  - IM
MH  - Animals
MH  - Anti-Bacterial Agents/*pharmacology
MH  - *Carbon-Carbon Ligases
MH  - Heterocyclic Compounds/*pharmacology
MH  - In Vitro Techniques
MH  - Ligases/*metabolism
MH  - Male
MH  - Microsomes, Liver/drug effects/*enzymology
MH  - Rats
MH  - Rats, Inbred Strains
MH  - Sulfhydryl Compounds/*pharmacology
MH  - Sulfhydryl Reagents/pharmacology
MH  - Vitamin K/*metabolism
MH  - beta-Lactams
EDAT- 1988/02/01 00:00
MHDA- 1988/02/01 00:01
CRDT- 1988/02/01 00:00
PHST- 1988/02/01 00:00 [pubmed]
PHST- 1988/02/01 00:01 [medline]
PHST- 1988/02/01 00:00 [entrez]
AID - 10.1254/jjp.46.165 [doi]
PST - ppublish
SO  - Jpn J Pharmacol. 1988 Feb;46(2):165-72. doi: 10.1254/jjp.46.165.