Allosterically coupled multi-site binding of T to human serum albumin

madman · Jul 24, 2022

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madman · Saturday at 10:50 AM

* the experimental data does not conform to the linear model (Vermeulen) of testosterones binding and we've shown this also for estradiol, so both for estradiol and testosterone the experimental data do not conform to the linear model, in addition what we have found is that the apparent binding affinity varies dynamically with changes in estradiol and SHBG concentrations

Implications of the Inter-monomeric Allostery and Dynamic Changes in Binding Affinity of SHBG and Albumin

Physiologic Implications:

Inter-monomeric allostery in SHBG extends the range of hormone concentrations that SHBG can bind and confers versatility in ligand binding.

Clinical Implications:

- Legacy linear models/equations unlikely to estimate free T or E2 accurately:

- Direct measurements of free T by equilibrium dialysis is ideal, but the binding models that consider the inter-monomeric allostery, the influence of other hormones, can provide better approximation.

The Binding Isotherms of Testosterone Binding to SHBG Exhibit a Multiphase Profile and Do not Conform to a Single Kd

Apparent Kd of Estradiol's Binding to SHBG Changes Dynamically with SHBG and E2 Concentrations and Involves Inter-Monomeric Allostery

Implications of the Inter-monomeric Allostery and Dynamic Changes in Binding Affinity of SHBG and Albumin

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