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Specificity and
selectivity of
hormone receptors
Chemical composition
Mechanism of action/
location of receptor
Solubility properties
Classification of hormones based on
chemical composition
Cholesterol derivatives
Tyrosine derivatives T3, T4
Peptides Insulin
Glycoprotein
Cholesterol derivatives hormone
Cell
surface
receptor
Intracellular
receptor
Hormonal involvement in responses to a stimulus
I. Hormones that bind to intracellular receptors
Androgens
Calcitriol (1,25[OH]2-D3)
Estrogens
Glucocorticoids
Mineralocorticoids
Progestins
Retinoic acid
Thyroid hormones (T3 and T4)
II. Hormones that bind to cell surface
receptors
II. Hormones that bind to cell surface
receptors
Clinical Importances
HYPERTHYROID HYPOTHYROID
EXOPHTHALMUS
DIABETES MELLITUS Hyperglycemia
The endocrine system of the pancreas
HORMONES OF THE PANCREAS
Harper’s Biochemistry
ROLE OF INSULIN :
1. Induce glycolysis
2. Inhibit gluconeogenesis
3. Increase glucose uptake GLUT 4
4. Increase glycogenesis
5. Inhibit lipolysis
6. Increase protein synthesis
Effect of insulin
Harper’s Biochemistry
GLYCOLYSIS REGULATION
Harper’s Biochemistry
GLUCONEOGENESIS REGULATION
Enzyme of Inducer Repressor Activator Inhibitor
gluconeogenesis
Glucose -6- Glucagon Insulin
phosphatase Epinefrin
(cAMP)
Glucocorti
coid
Fructose-1,6- Idem Insulin Glucagon Fruc-1,6-
biphosphatase (cAMP) biphosphate,
Fruc-2,6
biphosphate,
AMP
Harper’s Biochemistry
Regulation of PDH kinase and PDH fosfatase
GLYCOGENESIS
ACTH, TSH, INSULIN
ADRENALINE GLUKAGON
NORADRENALINE
hormon sensitive
- Lipase (TG lipase)
ATP
Β-Blocker Adre- + + - ( inactive)
nalin
H. THYROID ADENYLATE + Insulin
+ -
CYCLASE Protein kinase
Lip. Fosfatase
-
INHIBITOR cAMP + (dependent - TG
GH -
ADENOSINE cAMP)
PHOSPHODIESTERASE
hormon sensitive
METIL XANTIN, - -
Lipase (TG lipase) FFA
CAFEIN, TEOFI – + 5AMP
LINE (active)
INSULIN +
- DG
H. THYROID
-
GLUKOKORTIKOID 2 FFA
Hormon sensitive lipase (TG Inhibitor
GLYCEROL
lipase) regulation in adipose
Glucagon’s Metabolic effect
Insulin and Glucagon actions
THYROID HORMONE
T3 : 3,5,3’-TRIIODOTHYRONINE
TYROSINE DERIVATE
T4 : 3,5,3’,5’-TETRAIODOTYRONINE (THYROXINE)
6 major steps:
1. active transport of I– across the basement membrane into
the thyroid cell (trapping);
2. oxidation of iodide and iodination of tyrosyl residues in
thyroglobulin (organification);
3. linking pairs of iodotyrosine molecules within
thyroglobulin to form the iodothyronines T3 and T4
(coupling);
4. proteolysis of thyroglobulin, with release of free
iodothyronines into the circulation;
5. deiodination of iodotyrosines within the thyroid cell, with
conservation and reuse of the liberated iodide;
6. intrathyroidal 5'-deiodination of T4 to T3.
IODIDE METABOLISM
- OXIDATION OF IODIDE : I- TO I+
PTU
NIS
Thyroid
Hormone
synthesis
Thyroid hormone transport proteins
There are three major thyroid hormone transport proteins:
thyroxine-binding globulin (TBG) : 70%
transthyretin or thyroxine-binding prealbumin (TBPA) :
20%
albumin (10%)
CAUSED BY :
IODIDE DEFICIENCY
IODIDE TRANSPORT DEFECT
IODINATION DEFECT
COUPLING DEFECT
DEIODINASI DEFICIENCY
PRODUCTION OF ABNORMAL IODINATION PROTEIN
GOITER
TSH
THYROID HORMONE
INSUFFICIENT OF T3 AND T4
CRETINISM
HYPERTHYROIDSM
(GRAVE’S DESEASE)
UNCONTROLLED T3 T4 PRODUCTION
NERVOUSNESS
INABILITY TO SLEEP
INCREASE APPETITE
WEIGHT LOSS
EXCESSIVE SWEATING
SENSITIVE TO HEAT
WEAKNES