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Enzymes involved in the formation of 4‐hydroxy‐acyl‐CoA esters from γ‐hydroxybutyrate (GHB) and γ‐hydroxypentanoate (GHP)
Author(s) -
Zhang Guofang,
Kasumov Takhar,
David France,
Anderson Ver E.,
Brunengraber Henri
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1016.6
Subject(s) - metabolite , enzyme , microsome , cytosol , chemistry , acyl coa , biochemistry , gamma hydroxybutyrate , pharmacology , medicine
GHB is both a brain metabolite and a drug of abuse (date rape drug). GHP, a GHB analog, is also a drug of abuse. During EB 2007, we reported the identification of 4‐phospho‐butyryl‐CoA (P‐GHB‐CoA) and 4‐phospho‐pentanoyl‐CoA (P‐GHP‐CoA) in liver, kidney and brain of rats injected with GHB or GHP. We perfused livers with fatty acids (C3 to C5) hydroxylated on various carbons. HPLC‐MS‐MS‐ESI analysis showed that phosphoacyl‐CoAs are formed only from 4‐hydroxyacids. Using LC‐MS/MS assays, we searched for liver enzymes involved in the formation of P‐GHB‐CoA and P‐GHP‐CoA. Enzyme activity catalyzing the formation of GHB‐CoA or GHP‐CoA from the free acids is present in cytosol, mitochondria and microsomes. The phosphorylation of GHB‐CoA or GHP‐CoA occurs only in the cytosol, and is concentrated in the 15 to 35% ammonium sulfate fraction. Supported by NIH grant ES013925.