PMID- 1970779
OWN - NLM
STAT- MEDLINE
DCOM- 19900614
LR  - 20131121
IS  - 0090-9556 (Print)
IS  - 0090-9556 (Linking)
VI  - 18
IP  - 1
DP  - 1990 Jan-Feb
TI  - Thiol-mediated catalysis of nitroglycerin degradation by serum proteins. Increase 
      in metabolism was not accompanied by S-nitrosothiol production.
PG  - 61-7
AB  - In vitro degradation of nitroglycerin (NTG) in human plasma has been shown to be 
      accelerated significantly by sulfhydryl compounds. The interaction between NTG 
      and N-acetyl-1-cysteine (NAC) in human plasma produces a pharmacologically active 
      S-nitrosothiol, which may be responsible, at least in part, for the in vivo 
      nitrate tolerance-reversing effect of NAC. The mechanism of this thiol-mediated 
      NTG degradation in plasma has not been identified. In this report, we examined 
      the catalytic activity of various plasma proteins toward NAC-mediated NTG 
      degradation and found human serum albumin (HSA) to have the highest catalytic 
      activity among the proteins tested. However, the dinitrate metabolite 
      distribution ratio found with HSA (favoring the 1,3- over the 1,2-isomer) was 
      substantially different from that observed with human plasma (where equal amounts 
      of both dinitrates were produced). In addition, the HSA-catalyzed degradation of 
      NTG did not lead to enhanced formation of S-nitrosothiol. These findings 
      therefore argue against a predominant role exerted by HSA in the thiol-mediated 
      NTG metabolism in plasma. The HSA-mediated catalysis of NTG was partially blocked 
      by pretreatment with NAC followed by a thiol-alkylating agent, suggesting that 
      the catalytic mechanism was due, in part, to the conversion of disulfide linkages 
      within the HSA structure to reactive sulfhydryl groups.
FAU - Chong, S
AU  - Chong S
AD  - Department of Pharmaceutics, School of Pharmacy, State University of New York, 
      Buffalo 14260.
FAU - Fung, H L
AU  - Fung HL
LA  - eng
GR  - GM-42850/GM/NIGMS NIH HHS/United States
GR  - HL 22273/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Drug Metab Dispos
JT  - Drug metabolism and disposition: the biological fate of chemicals
JID - 9421550
RN  - 0 (Blood Proteins)
RN  - 0 (Nitroso Compounds)
RN  - 0 (S-Nitrosothiols)
RN  - 0 (Serum Albumin)
RN  - 0 (Sulfhydryl Compounds)
RN  - 60-24-2 (Mercaptoethanol)
RN  - 67616-44-8 (S-nitrosomercaptoethanol)
RN  - G59M7S0WS3 (Nitroglycerin)
RN  - WYQ7N0BPYC (Acetylcysteine)
SB  - IM
MH  - Acetylcysteine/metabolism
MH  - Blood Proteins/*metabolism
MH  - Catalysis
MH  - Humans
MH  - *Mercaptoethanol
MH  - Nitroglycerin/*blood
MH  - Nitroso Compounds/*metabolism
MH  - Protein Binding
MH  - *S-Nitrosothiols
MH  - Serum Albumin/metabolism
MH  - Sulfhydryl Compounds/*metabolism
EDAT- 1990/01/01 00:00
MHDA- 1990/01/01 00:01
CRDT- 1990/01/01 00:00
PHST- 1990/01/01 00:00 [pubmed]
PHST- 1990/01/01 00:01 [medline]
PHST- 1990/01/01 00:00 [entrez]
PST - ppublish
SO  - Drug Metab Dispos. 1990 Jan-Feb;18(1):61-7.