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Mr. Clean
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PostPosted: Fri Apr 29, 2011 9:01 am    Post subject: Mechanism of coal Tar for DHT Inhibition Reply with quote

http://www.hairloss-research.org/UpdateCOAL-TAR4-10.html

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[...]

It is this investigator's finding that a specific co-enzyme present in coal tar serves to block the conversion of DHA and testosterone to DHT.

In vivo studies demonstrated that hair loss was significantly retarded with regular application of a coal tar formulation.

An initial comparative study of published findings on alopecia and review of coal tar applications for dermatological disease treatment revealed no explanation for the activity cited above to i.e., the inhibition of the conversion of testosterone to dihydrotestosterone. However, the study of the co-enzymes required for this reaction, namely the interaction of 5a-reductase and NADP (nicotinamide adenine dinucleotide phosphate) revealed a mechanism of action that would explain lower levels of DHT is patients regularly applying the coal tar solution. The conversion of testosterone to DHT is catalyzed by 5a-reductase which serves to donate the extra hydrogen atom carried by DHT. To release this atom, 5a-reductase requires the presence of the co-enzyme NADP.

To clarify this point, it may be helpful to review the role of enzymes in human metabolism. Enzymes are protein molecules of high molar mass which serve to catalyze reactions, making it possible for changes to occur faster and/or with reduced levels of energy. Most enzymes contain a non-protein element called a co-enzyme that must be present if the enzyme is to fulfill its function. In some cases, the co-enzyme is a metal cation such as Zn2 , Cu2 or Co2 . In others, it is an organic molecule, most often a vitamin (such as the B vitamin niacin). DHT is a ligand. Ligands are molecules which are bonded to the central metal in a complex ion (ligands can also be defined as any molecule with an unshared pair of electrons). DHT requires an extra hydrogen atom to convert from testosterone. If this extra hydrogen atom is not available, the conversion cannot occur. Testosterone uses 5a reductase as its substrate. This substrate is one of the family of dehydrogenases, a class of enzymes which serve to remove two electrons and two hydrogen ions from the substrate. Dehydrogenases are very specific to their substrate. The electron acceptor for some dehydrogenases is NADP.sup. , others Use NAP.sup. . If this acceptor is deactivated by the presence of coal tar, as is generally recognized (See U.S. Pat. No. 4,102,0995 to Peter Hebborn, Jul. 25, 1978, entitled Tar Gel Formulation, cited below), then the catalytic function of 5a-reductase is inhibited.

The patent excerpt above concerned itself with tar gel formulation and makes reference to the inhibition of the co-enzyme NADP found in coal far as the mechanism of action for the retardation of excessive skin cell reproduction occurring in psoriasis conditions. LCD, a liquid, diluted form of coal tar gel, is likely to have the same or similar inhibiting action on NADP within the cellular metabolism of the hair follicle cells and sebaceous glands. With the deactivation of NADP, 5a-reductase is disabled as the catalyst for T/DHT conversion. The diagram below details the metabolic pathway in human skin of testosterone to dihydrotestosterone.

The importance of the role of dehydrogenase activity within the sebaceous glands of scalp tissue exhibiting androgenic alopecia is documented by Marty E. Sawaya, et. al., in her published article, "-- 5-3β-Hydroxysteroid Dehydrogenase Activity in Sebaceous Glands of Scalp in Male-Pattern Baldness" (The Society for Investigative Dermatology, December 1987). Their work suggests that bald areas of the scalp have a greater propensity for converting testosterone into DHT through the heightened activity of another dehydrogenase, -- 5-3β-Hydroxysteroid.

By way of example, it is suggested here that as women enter menopause and naturally-produced estrogen levels decline, they experience hair loss due to the concurrent rise in DHT which is no longer being inhibited or neutralized at the same rate due to the lower amounts of circulating estrogens. It is believed that the application of the coal tar solution at the onset of menopause or androgenic alopecia would serve to perform a similar metabolic function as the estrogens, limiting DHT production and its effects on deleterious DNA protein expression.

The mechanism of action in the Topical Lotion for the Retardation of Alopecia (patent application Ser. No. 08/343,647) to which this is a CIP, is thus primarily based on the single ingredient coal tar and the claims for its singular discovery as a retardant to androgenic alopecia should be reconsidered in light of its inhibition of the essential co-enzyme NADP in the catalytic role of the 5a-reductase substrate for T to DHT conversion.


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Mr. Clean
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PostPosted: Sat Apr 30, 2011 8:25 am    Post subject: Reply with quote

Coal Tar discussions...


http://www.hairlosstalk.com/interact/viewtopic.php?f=32&t=41243



http://www.hairlosstalk.com/interact/viewtopic.php?f=11&t=32940
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Mr. Clean
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PostPosted: Mon May 02, 2011 12:19 am    Post subject: Reply with quote

http://www.freepatentsonline.com/5609858.html

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Coal tar is credited with an inhibitory action on the pentose cycle in cellular metabolism, which is particularly active in psoriasis. As a result there is a reduction in the activity of the enzymes G6PD and NADP. This inhibitory action is said to reduce DNA and RNA synthesis, resulting in the inhibition of mitotic activity and protein synthesis. A reduction of mitosis, or cell division, is beneficial to the psoriasis patient because . . . one of the factors in psoriasis is the extreme acceleration of epidermal cell production.




5 alpha reductase requires NADP as a co-factor in order to convert testosterone into DHT.
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