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Testosterone Replacement, Low T, HCG, & Beyond
Testosterone and Men's Health Articles
Allosterically coupled multi-site binding of T to human serum albumin
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<blockquote data-quote="madman" data-source="post: 189996" data-attributes="member: 13851"><p>The two Kd values resulting from the fit of the steady-state data (Figure 3B) are 17.8 nM and 12.3 µM, which differ by three orders of magnitude. The range of circulating testosterone concentration in men is 10-35 nM, that of HSA 450-750 µM, and that of SHBG 13.5-87.3 nM. With such high serum concentration of HSA, comparatively lower concentrations of testosterone and SHBG, and a high-affinity binding pocket on HSA in the low nanomolar range, virtually all of the testosterone in the blood would expect to be bound to HSA, with a negligible amount bound to SHBG or unbound to any protein. However, clinical data (13, 18, 48) show that 33- 45% of testosterone in the blood is bound to SHBG, while 50-67% is bound to HSA and 1-4% is unbound. The only explanation for this, while staying consistent with the derived dissociation constant values from our data, is that the low-affinity site with a Kd of 12.3 µM is the only available site on HSA in the unbound state. The binding of testosterone to the low-affinity binding site causes a long-range conformational change that renders the second, high-affinity binding site available for binding testosterone. <strong><em>We have previously observed similar allosteric coupling between the monomers of dimeric SHBG upon testosterone binding (49). <span style="color: rgb(184, 49, 47)"><u>The overly simplified linear models with 1:1 stoichiometry have overlooked the complexities in the dynamics of the binding of testosterone to HSA and SHBG</u>.</span> </em></strong></p></blockquote><p></p>
[QUOTE="madman, post: 189996, member: 13851"] The two Kd values resulting from the fit of the steady-state data (Figure 3B) are 17.8 nM and 12.3 µM, which differ by three orders of magnitude. The range of circulating testosterone concentration in men is 10-35 nM, that of HSA 450-750 µM, and that of SHBG 13.5-87.3 nM. With such high serum concentration of HSA, comparatively lower concentrations of testosterone and SHBG, and a high-affinity binding pocket on HSA in the low nanomolar range, virtually all of the testosterone in the blood would expect to be bound to HSA, with a negligible amount bound to SHBG or unbound to any protein. However, clinical data (13, 18, 48) show that 33- 45% of testosterone in the blood is bound to SHBG, while 50-67% is bound to HSA and 1-4% is unbound. The only explanation for this, while staying consistent with the derived dissociation constant values from our data, is that the low-affinity site with a Kd of 12.3 µM is the only available site on HSA in the unbound state. The binding of testosterone to the low-affinity binding site causes a long-range conformational change that renders the second, high-affinity binding site available for binding testosterone. [B][I]We have previously observed similar allosteric coupling between the monomers of dimeric SHBG upon testosterone binding (49). [COLOR=rgb(184, 49, 47)][U]The overly simplified linear models with 1:1 stoichiometry have overlooked the complexities in the dynamics of the binding of testosterone to HSA and SHBG[/U].[/COLOR] [/I][/B] [/QUOTE]
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Testosterone Replacement, Low T, HCG, & Beyond
Testosterone and Men's Health Articles
Allosterically coupled multi-site binding of T to human serum albumin
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