Reactome | SERPINA6 binds PREDL

SERPINA6 binds PREDL

Stable Identifier

R-HSA-9757686

Type

Reaction [binding]

Species

Homo sapiens

Compartment

extracellular region

ReviewStatus

5/5

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Prednisolone (PREDL) reversibly binds to transcortin (corticosteroid-binding globulin, CBG, SERPINA6) (Pugeat et al, 1981). The affinity of prednisolone (PREDL) to SERPINA6 is higher than that of PREDN, and PREDN is displaced by PREDL in concentrations above 5:1 excess of PREDL (Ferry and Wagner, 1987; Boudinot and Jusko, 1984). The binding sites for PREDN and PREDL are different (Legler and Benet, 1986). With therapeutic PREDN doses, PREDL plasma concentrations exceed those of PREDN by four to tenfold (Rose et al, 1981).

The capacity of SERPINA6 to bind PREDN and PREDL is limited, with albumin (ALB) weakly binding the excess. Steroids bound to SERPINA6 are released when local conditions, like the proteolytic milieu of inflamed tissue, change the allosteric configuration of SERPINA6 (Zhou et al, 2008, reviewed by Henley et al, 2016).

Literature References

PubMed ID	Title	Journal	Year
27411675	Cortisol and CBG - Getting cortisol to the right place at the right time Henley, D, Carrell, R, Lightman, S	Pharmacol Ther	2016
6492791	Plasma protein binding interaction of prednisone and prednisolone Boudinot, FD, Jusko, WJ	J Steroid Biochem	1984
7195405	Transport of steroid hormones: interaction of 70 drugs with testosterone-binding globulin and corticosteroid-binding globulin in human plasma Nisula, BC, Pugeat, MM, Dunn, JF	J Clin Endocrinol Metab	1981
18513745	The S-to-R transition of corticosteroid-binding globulin and the mechanism of hormone release Stanley, PL, Read, RJ, Wei, Z, Carrell, RW, Stein, PE, Zhou, A	J Mol Biol	2008
3709632	The effect of prednisone and hydrocortisone on the plasma protein binding of prednisolone in man Legler, UF, Benet, LZ	Eur J Clin Pharmacol	1986
7310640	Dose dependent pharmacokinetics of prednisone and prednisolone in man Yurchak, AM, Jusko, WJ, Rose, JQ	J Pharmacokinet Biopharm	1981
7400951	Serum protein binding of prednisolone in four species Rocci, ML, Johnson, NF, Jusko, WJ	J Pharm Sci	1980
3593903	The nonlinear pharmacokinetics of prednisone and prednisolone. II. Plasma protein binding of prednisone and prednisolone in rabbit and human plasma Ferry, JJ, Wagner, JG	Biopharm Drug Dispos	1987