Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Nafenopin-, ciprofibroyl-, and palmitoyl-CoA conjugation in vitro: Kineticand molecular characterization of marmoset liver microsomes and expressed MLCL
Autore:
Drogemuller, CJ; Nunthasomboon, S; Knights, KM;
Indirizzi:
Flinders Univ S Australia, Fac Hlth Sci, Sch Med, Dept Clin Pharmacol, Bedford Pk, SA 5042, Australia Flinders Univ S Australia Bedford Pk SA Australia 5042 SA 5042, Australia
Titolo Testata:
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
fascicolo: 1, volume: 396, anno: 2001,
pagine: 56 - 64
SICI:
0003-9861(200112)396:1<56:NCAPCI>2.0.ZU;2-C
Fonte:
ISI
Lingua:
ENG
Soggetto:
CHAIN FATTY-ACID; XENOBIOTIC CARBOXYLIC-ACIDS; PROTEIN KINASE-C; COENZYME-A; ACYL-COENZYME; RAT-LIVER; PEROXISOME PROLIFERATION; HYPOLIPEMIC DRUGS; GENE-EXPRESSION; SYNTHETASE GENE;
Keywords:
nafenopin; ciprofibrate; xenobiotic conjugation with CoA; long-chain fatty acid CoA ligases; marmoset liver microsomes; recombinant protein;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
48
Recensione:
Indirizzi per estratti:
Indirizzo: Knights, KM Flinders Univ S Australia, Fac Hlth Sci, Sch Med, Dept Clin Pharmacol, Bedford Pk, SA 5042, Australia Flinders Univ S Australia Bedford Pk SA Australia 5042 tralia
Citazione:
C.J. Drogemuller et al., "Nafenopin-, ciprofibroyl-, and palmitoyl-CoA conjugation in vitro: Kineticand molecular characterization of marmoset liver microsomes and expressed MLCL", ARCH BIOCH, 396(1), 2001, pp. 56-64

Abstract

Acyl-CoA conjugation of xenobiotic carboxylic acids is catalyzed by hepatic microsomal long-chain fatty acid CoA ligases (LCL, EC 6.2.1.3). Marmosets(Callithrix jacchus) are considered genetically closer to humans than rodents and are used in pharmacological and toxicological studies. We have demonstrated that marmoset liver microsomes catalyze nafenopin-, ciprofibroyl-,and palmitoyl-CoA conjugation and that only palmitoyl-CoA conjugation is significantly upregulated (1.7-fold, P < 0.02) by a high fat diet. Additionally, the apparent C-50 values for nafenopin-, ciprofibroyl-, and palmitoyl-CoA conjugation of 149.7,413.4, and 3.4 muM were comparable to those reported for human liver microsomes viz, 213.7, 379.8, and 3.4 muM, respectively. Comparison with human data was enabled by the cloning of a full-length marmoset cDNA (MLCL1) that encoded a 698-amino-acid protein sharing 83% similarity with rat liver acyl-CoA synthetase (ACS1) and 93 and 90% similarity with human liver LCL1 and LCL2, respectively. MLCL1 transiently expressed in COS-7 cells activated nafenopin (C-50 192.9 muM), ciprofibrate (C-50 168.7 muM), and palmitic acid (C-50 4.5 muM) to their respective CoA conjugates. This study also demonstrated that the sigmoidal kinetics observed for nafenopin- and ciprofibroyl-CoA conjugation were not unique to human liver microsomes but were also characteristic of marmoset liver microsomes and recombinant MLCL1. More extensive characterization of the substrate specificity ofmarmoset LCL isoforms will aid in determining further the suitability of marmosets as a model for human xenobiotic metabolism via acyl-CoA conjugation. (C) 2001 Elsevier Science.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/03/20 alle ore 00:04:02