Biochem 3

Question 1

What are the three classes of steroid hormones, and where are they derived from?

Answer 1

All come from the adrenal cortex:
Glucocorticoids (Cortisol)
Mineralocorticoids (aldosterone)
Adrenal androgens (DHEA, Androstenedione)

Question 2

What are the Catecholamines and where are they produced?

Answer 2

They are Tryosine-derived hormones –> Epinephrine, Norepinephrine, Dopamine.
They are produced in the adrenal medulla

Question 3

Where do steroid hormones come from? (precursors - steps)

Answer 3

Cholesterol –> Pregnenolone (in mitochondrion)= common precursor
Prenenolone –> Progesterone
–> Deoxycortisol –> cortisol

Enzymes: P450scc, CYP17,21,11B, 3 Beta HSD

Question 4

What stimulates cortisol synthesis? How?

Answer 4

ACTH
ACTH binds to GPCR - works through AC/cAMP/PKA –> So, G alpha S
PKA cause conversion of cholesterol ester (storage form) into cholesterol via cholesterol esterase

Question 5

Genomic effects of ACTH

Answer 5

Increase in activity and expression of:

Cholesterol esterase, CYP 11, CYP 17, LDL receptors on surface –> All to increase glucocorticoid synthesis

Question 6

Non-Genomic effects of ACTH

Answer 6

Mobilize glucose to liver
Break down fats/proteins
Maintain Blood volume
Inhibit prostaglandin synthesis

Question 7

How do we find cortisol? (percentages)

Answer 7

10% is free in serum
75% bound to CBP (produced in liver - binds to cortisol with high affinity)
15% bound to albumin

Question 8

What is the deal with Cortisol-Cortisone Shunt?

Answer 8

It prevents cortisol from binding the mineralcorticoid receptor - which can bind both cortisol and aldosterone (cortisol = 1000x more affinity)

Question 9

Describe how the cortisol-cortisone shunt pathway works

Answer 9

• Cortisol is the active form
• Gets to kidney –> turned into cortisone (inactive) by 11-Beta-HSDII (now can’t bind to MR)
• Cortisone then leaves the kidney - into circulation - it can be reversed by HSD1

Question 10

What is Apparent Mineralocorticoid excess (AME)

Answer 10

• The enzyme (11-Beta-HSDII) that converts cortisol to cortisone is blocked.
• Cortisol in the kidney can now bind to MR - has an aldosterone like function –> HYPOKALEMIA AND HYPERTENSION
• Seen with liquorice overdose

Question 11

What do we see in the urine due to cortisol Metabolism?

Answer 11

Tetrahydrocortisol or Tetrahydrocortisone

Question 12

What cause’s Cushing’s Syndrome?

Answer 12

Excess of Glucocorticoids

Question 13

Difference between Cushing’s Syndrome and Cushing’s Disease?

Answer 13

If it is the BODY producing too much cortisol = DISEASE

Question 14

Signs and symptoms of Cushing’s Syndrome?

Which are all due to corisol’s effect on metabolism

Answer 14

HTN in ~80%
Moon Facies
Osteoporosis
Buffalo hump, Obesity
Adrenal tumor or hyperplasia
Thin, wrinkled skin
Amenorrhea
Muscle weakness

Question 15

What is the name of the disease linked to Adrenal insufficiency?

Answer 15

Addison’s Disease

Question 16

What causes Addison’s disease?

Answer 16

Damage to adrenal cortex

Question 17

Define (w/ example) Primary adrenal insufficiency:

Answer 17

Primary: Adrenal cortex not producing cortisol

- Will cause an increase in ACTH from the pituitary
 - Addison's Disease

Question 18

Signs and symptoms of Addison’s Disease:

Answer 18

• Changes in blood pressure or heart rate
• Chronic diarrhea/n/v or loss of appetite resulting in weight loss
• Darkening of the skin (B/C ACTH comes from POMC - which breaks down to MSH, LPH - which stimulates melatonin production)
• Extreme weakness, fatigue
• Mouth lesions on the inside of a cheek (buccal mucosa)
• Salt craving
• Hypoglycemia (hepatic glucose is not being moibilized into the blood
• Hypotension

Question 19

What is the cause of Congenital adrenal hyperplasia (CAH)?

Answer 19

Deficiency in 21 alpha hydroxylase (CYP21)

-Leads to insufficient aldosterone and cortisol production with excess of androgens and weak androgens

Question 20

What are the symptoms of Congenital adrenal hyperplasia?

Answer 20

Virilization of females in utero (ambiguous genitalia) from the excessive androgens
Lack of aldosterone causes salt-wasting; weight loss, lethargy, dehydration, death

Question 21

What does a 17 alpha hydroxylase deficiency cause?

Answer 21

Excess aldosterone

Deficient in cortisol and andorgens

Question 22

What stimulates the production of aldosterone?

Answer 22

• ACTH (via G alpha S - PKA –> CREB)

- Angiotensin II (IP3 - Ca - CREB)

Question 23

What is the predominate enzyme associated with mineralocorticoid (aldosterone) synthesis?

Answer 23

21-alpha-hydroxylase (CYP 21)

Question 24

How is aldosterone found?

Answer 24

Hydrophobic - 60% is bound weakly to CMP and albumin

-Binds weaker than cortisol

Question 25

What are the steps for the synthesis of catecholamines?

Answer 25

Phenylalanine --> Tyrosine --> Dopa --> Dopamine --> Noreepinenphrine --> Epinephrine Neurons: L-tyrosine --> Nor-epi Adrenal Medulla: L-tyrosine --> Epi

Question 26

How are Catecholamines stored?

Answer 26

Sequestered in storage vesicles (within the adrenal medulla) intracellularly -ATP is an important driver for this process

Question 27

What enzymes are important in the metabolism of norepinephrine and epinephrine?

Answer 27

MAO: Monoamine oxidase COMT: Catecho-o-methyltransferase

Question 28

What is a common metabolite in the metabolism of norepinephrine and epinephrine?

Answer 28

VMA: can be found in the urine | Vanillylmandelic acid

Question 29

What is a Pheochromactyoma?

Answer 29

Produce excess catecholamine from an abnormal growth of the adrenal medulla

Question 30

What are the symptoms of a Pheochromacytoma?

Answer 30

Headaches, HTN, diaphoretic, palpitations, tremor all due to excess catecholamine

Question 31

How do we diagnose a Pheochromacytoma?

Answer 31

Elevated VMA in the urine