It's a naturally occurring brain chemical with an unwieldy name:
4-hydroxybutyrate (4-HB). Taken by mouth, it can be abused or used
as a date-rape drug.
Now, a team of Ohio and Michigan scientists have determined new
routes by which 4-HB is metabolized by the body. "This is new and
important information," said K. Michael Gibson, professor and chair
of biological sciences at Michigan Technological University and a
member of the research team. "It may provide new clues on how to
counteract the drug's effects, or to enhance its metabolism and
decrease toxicity for chronic abusers or victims of sexual
assault."
Gibson is co-author with Guo-Fang Zhang and others in the
laboratory of Prof. Henri Brunengraber from the Department of
Nutrition at Case Western Reserve University School of Medicine of
a paper published online today by the Journal of Biological
Chemistry. Their findings will appear in as "paper of the week"
in the the print edition of the weekly journal on Nov. 27,
2009.
4-HB is a derivative of a major brain neurotransmitter in humans
and other species. . It occurs naturally in small amounts in the
brains of most animals and humans. In a rare genetic metabolic
disorder, 4-HB accumulates in extremely high levels, causing
significant developmental delays and seizures.
But 4-HB - also called gamma hydroxybutyrate or GHB - is best
known and most feared when it is taken orally, because it is a drug
that impairs the capacity to exercise judgment, like rohypnol and
ketamine hydrochloride.. For that reason, it can be used to
facilitate acquaintance sexual assault, commonly called date
rape.
Analyzing the chemicals produced by the breakdown of 4-HB in
mice and rats, Zhang, Gibson and colleagues used very sophisticated
mass spectrometry approaches to identify previously unknown enzymes
and pathways that appear to act on 4-HB and other similarly
structured compounds. They discovered that 4-HB is metabolized by
two different chemical mechanisms or pathways. Their discovery of
those pathways should open the door for future studies that can
identify the enzymes involved in the following steps of the
breakdown of 4-HB.
"This work may help to develop new antidotes and treatments for
people who have ingested 4-HB, as well as treatment for children
with the rare genetic disorder that causes the compound to
accumulate in high levels," Gibson said. (For more information on
genetic disorders of 4-HB, see www.pndassoc.org)
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