Biochemistry of the adrenal hormones Flashcards
What are the functions of the adrenal gland?
1) Aldosterone: Regulates the sodium and potassium balance
2) Cortisol: Regulates metabolism, increases blood glucose, and they are critical in the physiologic stress response
3) Androgens: Growth and development in both genders (it will produce other hormones like testosterone and estrogen)
4) The adrenal medulla will secrete catecholamines (The adrenal medulla is the principle site for the conversion of tyrosine into catecholamines “epinephrine, norepinephrine, and dopamine”)
What is the precursor of the adrenal cortex hormones?
Cholesterol
What is the precursor of the adrenal medulla hormone?
Tyrosine (AA)
What are the sources of cholesterol for the synthesis of steroids?
1) Endogenous synthesis:
- From the Acetyl-CoA via HMG-Synthase
- Exogenous source: Diet
What are the forms by which the lipid exists in our body?
1) Free
2) Stored in lipid droplets as esterified cholesterol (hydrolyzed by esterase upon stimulation with ACTH)
What is the process of steroid hormone synthesis?
1) Non-esterified cholesterol is transported into the mitochondria via STAR (Steroidogenic acute regulatory protein)
2) In the mitochondria cytochrome P450 side chain cleavage enzyme (P450scc) will convert cholesterol which has 27 carbon atoms to pregnenolone which has 21 carbon atoms
- It occurs in the mitochondria and endoplasmic reticulum
What is the requirement for synthesizing mineralocorticoids, glucocorticoids, and adrenal androgens?
1) Cytochrome P450 monooxygenase for hydroxylation (it cuts the side chain and oxidizes the cholesterol)
2) Monooxygenase requires NADPH as a cofactor
3) Dehydrogenase
4) Isomerase and lyases
Mnemonic for steroid hormone synthesis
- Mighty steroid synthesis STARts in the mitochondria
- You pay 450sccents to get Pringles
Pringles are ages 21 and older, pringle responsibly - NADA loves Pringles yumyum- they call her NADPHringles
- Isomi and Lyan love Pringles too yum-yum
- Pringles and endomie are dehydrated
What is the most important step in the synthesis of cholesterol?
- The conversion of Progesterone to Deoxycorticosterone via the enzyme 21-Hydroxylase
- Star carries cholesterol to mitochondria
What is the cellular route for the synthesis of cortisol?
1) ACTH will bind to the Gs protein producing cAMP
2) cAMP will activate protein kinase
3) At the same time LDL will bind to the LDL receptor and it will be stored in lipid droplets
4) The protein kinase A will activate esterase and convert cholesterol ester to cholesterol
5) Cholesterol will then be transported to the mitochondria via StaR
6) Cholesterol will then be converted to pregnenolone in the mitochondria which will go to the ER as progesterone
7) The progesterone will be converted to Deoxycortisol via 21-hydroxylase
8) Which will then be transported back to the mitochondria as cortisol
How do adrenal steroids (mineralocorticoids, glucocorticoids, and androgens) exert their function?
- They are transported in the blood via binding to albumin, globulins and other specific steroid proteins like Transcortin
- They then cross the membrane to bind to their intracellular receptors, alerting gene transcription
- Adrenal glands hormone + gonadal hormone have cytosolic hormones
What is the effect of cortisol on adipose tissue?
Acutely it will induce lipolysis, but in chronic elevations, it will promote lipogenesis, which can lead to visceral fat accumulation
What stimulates the synthesis of aldosterone?
- It shares the same synthetic pathway as cortisol
- It is stimulated by:
1) Increase in plasma Angiotensin-II
2) Increase in plasma ACTH
3) Increase in plasma K+
What are the actions of aldosterone?
1) Conserves sodium
2) Secretes potassium
3) Retains water
4) Stabilizes BP
What are the catecholamines?
- Dopamine, Epinephrine, Norepinephrine
Where is dopamine and norepinephrine synthesized?
In the CNS
Where is Epinephrine synthesized?
The methylated version of Norepinephrine is synthesized in the adrenal medulla
What is the function of the catecholamines?
They regulate the metabolism of carbohydrate and lipid metabolism, by degrading glycogen into glucose (causing hyperglycemia)
What type of receptor does epinephrine work by?
G-protein coupled receptors (2nd messenger)
What are the steps of the synthesis of catecholamines?
1) Tyrosine is converted to L-DOPA, via tyrosine oxidase (and this is the rate-limiting step)
2) L-DOPA is then converted to Dopamine
3) Dopamine is then converted to norepinephrine
4) Norepinephrine is then converted to epinephrine
Describe the mechanism of action of the adrenergic receptors
- They work by increasing the levels of cAMP, leading to the activation of protein kinase A which will:
1) Increase the phosphorylation of phospholamban (regulates Ca2+ in the SR) via PKA
2) It leads to the phosphorylation of glycogen phosphorylase in the liver and skeletal muscles
What are the different abnormal adrenal cortical functions?
1) Cushing’s syndrome
2) Adrenogenital syndrome
3) Addison’s disease
4) Conn’s syndrome
What is Cushing syndrome?
- Hypersecretion of cortical hormone, without respecting the time of the day or stressors
- When cortisol is increased, aldosterone and androgens will also increase
What is the clinical picture of Cushing’s disease?
1) Adiposity:
- Deposition of fat in the face, neck, and trunk
- Moon-shaped face
- Buffalo hump
2) Weight gain
3) Na & H2O retention
4) K+ is lost (hypokalemia)
5) Hirsutism
