.*In general, levels of free T determined using the linear model systematically underestimated those determined using the ensemble allostery model (mean (sd) cFTZ = 647.1 (253.8) pmol/L and cFTV = 434.5 (163.8) pmol/L).
*There was an apparent correlation between cFTV and cFTZ (r=0.9, p<0.01) although the agreement decreased with higher mean free testosterone level (Figure 1A and 1B) and the values from the two methods could not be interconverted by a simple scalar multiple. Stratification according to quartiles of TT indicated that higher levels of TT contributed to the difference between the two free testosterone algorithms.
*Despite the differences in absolute levels, the algorithms suggested by Vermeulen et al. and Zakharov et al. were in general in agreement in relation to the survival outcomes (Figure 2). However, the algorithm by Zakharov et al. tended to be in closer agreement with the associations seen for total testosterone indicating that the algorithm is more dependent on the levels of total testosterone compared to the algorithm by Vermeulen et al. However, with findings from recent studies on crystal structure and multisite binding of testosterone with albumin (31, 32), it is conceivable that simplified assumptions in extant models should be examined in detail. It is unclear why the algorithm by Vermeulen et al. was largely independent of both the levels of SHBG, albumin, and total testosterone level in contrast to the algorithm by Zakharov.
[URL unfurl="true"]https://www.excelmale.com/forum/threads/allosterically-coupled-multi-site-binding-of-t-to-human-serum-albumin.22102/#post-190020[/URL]
*We have previously observed similar allosteric coupling between the monomers of dimeric SHBG upon testosterone binding (49). 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.
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*The first structure of SA in complex with a steroid sex hormone indicates that testosterone does not bind in the previously suggested first Sudlow site but rather in two sites known to bind fatty acids and drugs.
