Printer Friendly

Chemical switch cuts off melatonin.

Many jet-lagged travelers, eager to reset their internal body clocks, rely on timely doses of the natural hormone melatonin to trigger sleep. Now, researchers at Rockefeller University in New York have found a substance that may have the opposite effect, promoting wakefulness by switching off melatonin's production.

A compound synthesized by chemists Ehab M. Khalil and Philip A. Cole effectively blocks one of two enzymes required to produce melatonin in the brain. The compound could help researchers explore the details of melatonin synthesis and offer a way to see if a reduction in the hormone's levels affects the sleeping patterns of animals and people.

"It's really an unexplored area because we haven't had the tools to evaluate it before," says Cole. Melatonin, made primarily by the pineal gland in the brain, plays a role not only in sleep but also in aging and reproduction (SN: 5/13/95, p. 300).

The transformation of the neurotransmitter serotonin into melatonin begins with an enzyme called arylalkylamine N-acetyltransferase (AANAT). This enzyme binds to both serotonin and a molecule called acetyl-CoA, then attaches a fragment of acetyl-CoA to serotonin.

Cole and Khalil made their new compound by connecting the molecule tryptamine, which is very similar to serotonin, to a variant of acetyl-CoA. The enzyme AANAT should readily take up this molecule, they reasoned, because it looks so much like the serotonin-acetyl-CoA combination. "It wasn't a large leap of faith to think that ... we could generate a structure which would be a potent inhibitor," says Cole. The synthesized compound indeed binds to AANAT 1,000 times better than its usual targets do. The team reports its findings in the June 24 Journal of the American Chemical Society.

Cole and Khalil also learned that, in test tube experiments, a molecule found naturally in cells also blocks AANAT quite well. Called a fatty acyl-CoA, it resembles the synthesized tryptamine-CoA compound. Its inhibitory action could explain two earlier observations. People who fast for one or two days experience an increase in fatty acyl-CoA levels. Also, their melatonin production drops. The Rockefeller results may be "one way to put those two unconnected observations together," Cole says, although a link between AANAT and fatty acyl-CoA in the body remains speculative.

The study is "a stepping stone toward a novel class of inhibitor compounds that could be of clinical value," says David C. Klein of the National Institute of Child Health and Human Development in Bethesda, Md. "if you want to bring melatonin synthesis to a very low level, that might enhance alertness." Klein and his colleagues are working on blocking a process that destroys AANAT--yet another approach to regulating melatonin synthesis.
COPYRIGHT 1998 Science Service, Inc.
No portion of this article can be reproduced without the express written permission from the copyright holder.
Copyright 1998, Gale Group. All rights reserved. Gale Group is a Thomson Corporation Company.

Article Details
Printer friendly Cite/link Email Feedback
Author:Wu, Corinna
Publication:Science News
Article Type:Brief Article
Date:Jul 4, 1998
Words:441
Previous Article:Persistent pollutants face global ban.
Next Article:Ancient North American shoes step to fore.
Topics:


Related Articles
... But quenched by ubiquitous hormone.
Drug of darkness: can a pineal hormone head off everything from breast cancer to aging?
Hormone helps elderly sleep.
Does light have a dark side?: nighttime illumination might elevate cancer risk.
Melatonin lag for jet travelers.
Nighttime hormone helps starve cancers.
Power lines rewire avian hormone.
Winter depression may heed hormonal signal. (Science News of the week).
You are getting sleepy.... (Supplement Watch).

Terms of use | Privacy policy | Copyright © 2021 Farlex, Inc. | Feedback | For webmasters |