cholesterol

It is the most hydrophobic of all membrane lipids

3 six membered rings

1 five membered ring

Rings are carboxylic not aromatic, but remain in tact

Only has 1 hydroxy group

Desmolase converts Cholesterol to pregnolone

1. attaches hydroxy groups to carbons 21 and 22

2. and then cleaves the bond between them, 6 carbons are released as an aldehyde and no longer important

11 hydroxylase

21 hydroxylase

17 hydroxylase

11 hyroxylase

21 hydroxylase

18 hyroxylase

18 hydroxysteroid dehydrogenase

17α hydroxylase

c17-20 lyase

Progesterone

It is synthesized from cholesterol via desmolase and a dehydrogenase.

It is the precursor to the corticosteroids and the sex steroids

What is this?

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Cortisol (glucocorticoid)

This is synthesized from progesterone via 11, 21 and 17 hydroxylase

Remember: for each hydroxylase added it is an additional hydroxy group added to the structure.  Progesterone doesnt have any hydroxy groups, and cortisol has 3

Aldosterone (mineralcorticoid)

This is synthesized from progesterone via 11, 21, 18 hydroxylase and 18 hydroxysteroid dehydrogenase

Note: the difference between this structure and that of cortisol is the presence of an aldehyde group (CHO)

aromatase 

remember: the difference between androgens and estrogens is that estrogens have an aromatic ring (aromatase)

cytochrome p450 (heme)

NADH

molecular oxygen

remember: all steroid hydroxylations follow the same mechanism of action and thus require the same components

What is meant by the term monoxygenase reaction 

(steroid hydroxylations)

1. Fault of the physician for prescribing too many glucocorticoids

2. ACTH secreting pituitary tumor; causes ACTH to be released causing incrased amounts of glucocorticoids to be synthesized

excess glucocorticoids

 causes uneven fat distribution

licorice root prevents the formation of cortisol, which is glucocorticoid with mineralcorticoid activity, to cortisone, which only maintains glucocorticoid activity

This causes increased Na+ retention which leads to hypernatremia which leads to high blood pressure

(androgenital syndrome)

A deficiency of 21 (more common) or 11 hydroxylase.  Essentially inhibiting the production of the corticosteroids.  Androgens are still able to be produced.

Causes excretion of Na+ and retention of K+ (opposite of the aldosterone effect)

Due to the lack of corticosteroids, there is no inhibition of the pituitary gland, since it relies on a negative feedback mechanism from high corticosteroid concentrations

Thus there is increased ACTH production and increased androgen production which can result in female virilization

corticosteroids

Remember: androgens are not part of the negative feedback mechanism

1. Iodine

2. Tyrosine residues in the protein thryoglobulin located in the folicular lumen

They act to increase the BMR

They are essential to proper development and differentiation of cells in the human body.

thus they are necessary for growth and development

T4=6 days

T3= 1.5 days

hypothyroidism acquired as an adult.

Reduced BMR = sluggish

Subcutaneous edema due to too much hylauronic acid which results in swelling of connective tissue

Hypothyroidism acquired in childhood.

Worst than myxedema

Results in: mental deficiency and stunted growth

Newborn screening for this is mandatory

Hyperthyroidism

Remember: Thyroid hormones control BMR

2 polypeptide chains

A= 21 aa

B= 30 aa

1. ACTH

2. Oxytocin

3. vasopressin

4. endorphins

It is the primary translation product of the insulin gene.  It must be processed into mature insulin

Components: Signal peptide, A chain, B chain, and a C peptide

1. The signal peptide on the preproinsulin is cleaved

2. The c peptide portion of preproinsulin is removed via convertase, which works by recognizing a pair of basic amino acid residues on the preproinsulin molecule 

= mature insulin

The removal of the C peptide is necessary for processing of preproinsulin into mature insulin.

C peptide has no hormonal activity but is clinically important because for every insulin molecule produced there is a C peptide.

In the clinical lab it is the C peptide, not insulin, that is measured because it has a longer half life than insulin and it is a better marker of the amount of insulin made by the body in the case of diabetics who might receive external insulin (which in this case is pure and does not have a C peptide)

1. Vasoconstrictor, raises blood pressure

-IP3 system, contracting muscle

2. Norepinephrine and epinephrine both contribute the vasoconstricting effect.  Angiotensin II contributes to their release from the adrenal medulla, and norepinephrine from the symp. nerve terminals

3. Acts on the zona glomerilosa of the adrenal cortex path that makes aldosterone and stimulates it.  This will also cause a raise in blood pressure (retention of Na+)

1. preproinsulin -> insulin

2. Angiotensinogen -> angiotensin 1-> angiotensin II

1. renin (kidney); converts angiotensinogen to angiotensin I

2. converting enzyme; converts angiotensin I to angiotensin II

First it works to convert angiotensin I to angiotensin II

Also, it inactivates bradykinin, which is a vasodilator

Precursor= angiotensinogen which is made in the liver and has no biological properties

needed: radioactive labeled hormone, and an antibody for the hormone

1. patients serum is added to a tube that contains radiolabeled hormone and the antibody

2. the radiolabeled hormone will be displaced by hormone in the patients blood

3. Free hormone is then separated from the hormone bound to an antibody

4. radioactivity of either the free hormone or the hormone antibody complex is measure and compared to a calibration curve 

Use radioactive antibody that is directed to a different part of the hormone than the antibody

Sandwhich consists of antibody-hormone-radiolabeled antibody

1. Eicosatrienoic acid (omega-6 fatty acid)

2. arachidonic acid (omega-6 fatty acid)

3. eicosapentaenoic acid (omega-3 fatty acid) found in abundance in fish oil

What is this?

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Arachidonic acid

omega-6 fatty acid, which is the most important for prostaglandin synthesis

1. eicosatrienoic acid: omega-6 fatty acid

[image]

2. eicosapentaenoic acid is an omega-3 fatty acid

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It is an enzyme for the conversion of arachidonic acid to prostaglandins (and thromboxane and prostacyclin)

Monooxygenase: hydroxylases

dioxygenase: cyclooxygenase 

arachidonic acid

-cyclooxygenase

PGG2 (unstable)

-peroxidase

PGH2(first stable product) which is then converted to the other prostaglandins which are tissue specific

20 aa

1 ring

carboxyl group

ex:

[image]

Thromboxane A2

The subscript is indicative of the number of double bonds outside the ring

Ex: in PGE 2 there are 2 double bonds outside the ring

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1. Cox-1 in tissue other than leucocytes

2. Cox-2 in leucocytes, during inflamation

1. platelette aggreggation

2. vasodilation

3. uterine contraction (can be used to induce labor or abortion at any time)

4. inflammation, mediates swelling and pain

5. Fever

6. reduced gastric acid secretion, increases formation of mucus in the stomach so to provide protection for the stomach

Thromboxane reduces the cAMP levels to activate platelets.

Oxytocin: can be used to induce labor at the normal time of child birth only

PGE2 and PGE2α (prostaglandins) can be used to induce labor or abortion at any time during pregnancy

20 carbon acids

no ring structure

they inhibit cyclooxygenase, 

- arachidonic acid is still produced (which is not the case when using a steroid)

This will prevent the formation of prostaglandins but not leucotreines since we still have the production of arachidonic acid.

NSAIDs work to reduce:

inflammation

pain

fever

platelet aggregation and thrombus formation

they can cause gastritis and peptic ucler

Because they only stop the formation of prostaglandins not leucotrienes.  

Leucotrienes are responsible for the bronchial constriction 

NSAIDs

Because they block the formation of prostaglandins which cause all those things by inhibiting cyclooxygenase

ex: aspirin

Cox 2

Particularly if the patient has an astheroscelerotic lesion with lecucocytes and antinflamtory cells made by Cox 2.  By inhibiting Cox 2, it prevents the formation of prostacycline (PGI2), which means there is no antagonist for thromboxane formed in the platelette