Volume 90 Issue 41 | p. 43 | Concentrates
Issue Date: October 8, 2012

BPA Metabolite Has Bad And Good Sides

Bisphenol A metabolite strongly binds estrogen receptors and could be useful in drug design, modeling study confirms
Department: Science & Technology
News Channels: Environmental SCENE
Keywords: BPA, endocrine disrupter, toxicity, toxicology, metabolite
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Structural models show how MBP is shaped more like estradiol and binds better to estrogen receptors than BPA; BPA is too short for optimal binding.
Credit: UC San Diego School of Medicine
Model shows how MBP’s shape is more like that of BPA and thus a better binder to estrogen receptors, more like estradiol itself.
 
Structural models show how MBP is shaped more like estradiol and binds better to estrogen receptors than BPA; BPA is too short for optimal binding.
Credit: UC San Diego School of Medicine

A molecular modeling study suggests that the controversial polycarbonate plastic building block bisphenol A may be less problematic as an endocrine-disrupting compound than one of its metabolites (PLoS One, DOI: 10.1371/journal.pone.0046078). BPA structurally resembles estradiol and binds weakly to estrogen receptors. Thus, BPA is thought to disrupt estrogen signaling and has been associated with health problems, including cancer, diabetes, and childhood obesity. In a 3-D modeling study, Michael E. Baker and Charlie Chandsawangbhuwana of the University of California, San Diego, found that a BPA metabolite known as MBP, which has three more carbon atoms between the phenol rings than does BPA, fits better into estrogen receptors than BPA itself. Previous studies have found that MBP binds 1,000 times more strongly than BPA. But the structural basis for the higher affinity hasn’t been determined. The UCSD researchers discovered that MBP’s longer structure allows both ends of the molecule to interact with amino acids in the receptors, just like estradiol does. Because it is shorter, BPA contacts the receptors only at one end. MBP levels in people should be monitored for possible health concerns, Baker says. He also suggests MBP could be used as a template to develop drugs that bind estrogen receptors to treat conditions linked to abnormal estrogen activity, such as breast and prostate cancers.

 
Chemical & Engineering News
ISSN 0009-2347
Copyright © American Chemical Society
Comments
Bob Buntrock (Tue Oct 23 16:05:24 EDT 2012)
I've been wondering about the binding constants for BPA compared to estradiol. This article and others cited help greatly. I'm still looking for similar studies comparing estradiol, BPA, and soy sterols. I'll also be looking for studies on the extent of formation of MBP from BPA. These studies seem to be confined to the use of cell cultures rather than whole organs or organisms, which could make quite the difference.

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