University of Kentucky Researchers Design New Enzymes Which Effectively Metabolize Cocaine

New enzymes that are highly efficient in metabolizing cocaine have been identified and designed by researchers at University of Kentucky.

These high-activity cocaine-metabolizing enzymes could potentially prevent cocaine from producing physiological effects, and could aid in the treatment of drug dependency. The results of this study by Chang-Guo Zhan et al are published in the journal PLOS Computational Biology.

The effectiveness of the enzymes' work was evaluated through modeling cocaine pharmacokinetics, the study of the body's action on administered external substances, such as cocaine, when the enzyme exists in the body. As there is no FDA-approved anti-cocaine medication, the medical and social consequences of cocaine abuse have made the development of anti-cocaine medication a high priority. Administration of an enzyme to enhance cocaine metabolism has been recognized as a promising treatment strategy for overdose and abuse. A remarkable feature of the enzyme-based therapeutic approach is that one enzyme molecule can degrade many thousands of drug molecules per minute.

This pharmacokinetic modelling is a crucial step of enzyme-based therapy development for cocaine abuse. Furthermore, the general insights of the research should also be valuable for future development of an enzyme therapy for any addictive drug, as the general methodology of the modelling may be used to develop valuable models for evaluating the effectiveness of metabolic enzymes in detoxifying other drugs.

Ovaries Do Produce New Eggs in Adulthood

A new study has found that contrary to popular belief, ovaries do produce new eggs, or oocytes, during adulthood.

The notion of a "biological clock" in women arises from the fact that oocytes progressively decline in number as females get older, along with a decades-old dogmatic view that oocytes cannot be renewed in mammals after birth. After careful assessment of data from a recent study published in PLoS Genetics, scientists from Massachusetts General Hospital and the University of Edinburgh argue that the findings support formation of new eggs during adult life; a topic that has been historically controversial and has sparked considerable debate in recent years.

Eggs are formed from progenitor germ cells that exit the mitotic cycle, thereby ending their ability to proliferate through cell division, and subsequently enter meiosis, a process unique to the formation of eggs and sperm which removes one half of the genetic material from each type of cell prior to fertilization.

While traditional thinking has held that female mammals are born with all of the eggs they will ever have, newer research has demonstrated that adult mouse and human ovaries contain a rare population of progenitor germ cells called oogonial stem cells capable of dividing and generating new oocytes. Using a powerful new genetic tool that traces the number of divisions a cell has undergone with age (its 'depth') Shapiro and colleagues counted the number of times progenitor germ cells divided before becoming oocytes; their study was published in PLoS Genetics in February this year.

If traditional thinking held true, all divisions would have occurred prior to birth, and thus all oocytes would exhibit the same depth regardless of age. However, the opposite was found – eggs showed a progressive increase in depth as the female mice grew older.

In their assessment of the work by Shapiro and colleagues – published recently in a PLoS Genetics Perspective article – reproductive biologists Dori Woods, Evelyn Telfer and Jonathan Tilly conclude that the most plausible explanation for these findings is that progenitor germ cells in ovaries continue to divide throughout reproductive life, resulting in production of new oocytes with greater depth as animals age.

Although these investigations were performed in mice, there is emerging evidence that oogonial stem cells are also present in the ovaries of reproductive-age women, and these cells possess the capacity, like their mouse counterparts, to generate new oocytes under certain experimental conditions. While more work is needed to settle the debate over the significance of oocyte renewal in adult mammals, Woods and colleagues emphasize that "the recent work of Shapiro and colleagues is one of the first reports to offer experimental data consistent with a role for postnatal oocyte renewal in contributing to the reserve of ovarian follicles available for use in adult females as they age."

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