hyroid hormone synthesis Basolateral membrane PLC-DAG SH) TSHR IP3 Apical membrane MP 2 Na* Ala+ NIS I(iodinated 1 PDS 2K+ DEHAL1 H2O2 NADP+ Na/K-ATPase 3 Nat. NADPH DUOX2 MIT DUOX2A DIT ? T iodinated Hydrolysis Capillary Colloid
thyroid hormone synthesis
Structures of thyroid hormones Ho-3 CH2-CH--COOH Thyroxine (4) 3.5,3′,5′- Tetraiodothyronine Deiodinase 1 or 2 Deiodinase 3>2 (5'-Deiodination) (5-Deiodination) NH CH,-CH-COOH HO oy-CH-CH-COOH Tri-iodothyronine (3) Reverse T3 (rT3) 3.5, 3'-Triodothyronine 3, 3, 5'-Triodothyronine
Structures of thyroid hormones
CHARACTERISTIES OF CIRCULATING T4 AND T3 HORMONE PROPERTY 4 3 Serum concentrations Total hormone 8 ug/dL 0. 14 ug/dL Fraction of total hormone in the free form 0.02% 0.3% Free(unbound)hormone 21×10-12M 6×10-12M Serum half-life 7 d 0.75d Fraction directly from the thyroid 100% 20% Production rate, including peripheral conversion 90 ug/d 32 ug/d Intracellular hormone fraction 20% 70% Relative metabolic potency 0.3 Receptor binding 10-10M 10-11M Sites of T4 Conversion: liver, kidney, and other tissue
CHARACTERISTICS OF CIRCULATING T4 AND T3 Sites of T4 Conversion: liver, kidney, and other tissue
Carriers for Circulating Thyroid Hormones e >gg%of circulating Ta and T, is bound to plasma carrier proteins Thyroxine-binding globulin(TBG) 75 Transthyretin (TTR), also called thyroxine-binding prealbumin tbpa 10 -15% Albumin 7% High-density lipoproteins(hdl % Carrier proteins can be affected by physiologic changes, drugs, and disease
Carriers for Circulating Thyroid Hormones >99% of circulating T4 and T3 is bound to plasma carrier proteins Thyroxine-binding globulin (TBG) 75% Transthyretin (TTR), also called thyroxine-binding prealbumin (TBPA) 10%-15% Albumin 7% High-density lipoproteins (HDL) 3% Carrier proteins can be affected by physiologic changes, drugs, and disease
Free Hormone Concept Only unbound (free)hormone has metabolic activity and physiologic effects Free hormone is a tiny percentage of total hormone in plasma(about o03%T4; 0.3%T3) o Total hormone concentration Normally is kept proportional to the concentration of carrier proteins o Is kept appropriate to maintain a constant free hormone leve
Free Hormone Concept Only unbound (free) hormone has metabolic activity and physiologic effects Free hormone is a tiny percentage of total hormone in plasma (about 0.03% T4; 0.3% T3) Total hormone concentration Normally is kept proportional to the concentration of carrier proteins Is kept appropriate to maintain a constant free hormone level