Thyroid Hormone System / Iodine

1. Compare and contrast the biochemistry and symptoms of clinical hypothyroidism and hyperthyroidism (Graves Disease).

2. Explain the chemistry and significance of T₄ and T₃, and how a nutritionally required element, iodine, is incorporated into these molecules.

3. Delineate the biochemical steps in the biosynthesis of T₄ and T₃.

4. Identify the nutritional deficiency, specific enzyme defects and the immune causes of goiter.

5. Describe the biochemistry of the TRH-TSH-T₄ axis, with special reference to second messengers in target cells and general structures of hormones.

6. Draw the mechanism whereby T₄ is activated to T3 in peripheral target cells and via a nuclear receptor, T₃ induces transcription of genes coding for oxidative enzymes, Na-K-ATPase, GH, b-adrenergic receptors etc.

Calcium Homeostasis / PTH / Vitamin D

1. Describe the physiology of calcium homeostasis in terms of the feedback controls of PTH, CT and 1,25(OH)₂D₃ synthesis and release.

2. Explain how bone mineral (Ca²⁺) is both laid down to provide the strength of the endoskeleton and mobilized to maintain serum calcium levels.

3. List the pathophysiology of hyperparathyroidism, hypoparathyroidism, pseudohypoparathyroidism, rickets and osteoporosis.

4. Discuss the actions of calciotropic hormones at bone (osteoblasts and osteoclasts), kidney and intestine; develop the biochemical mechanisms in outline form.

5. List the general chemical compositions of PTH, CT and 1,25(OH)₂D₃ and differentiate how they arise biochemically from their respective precursors.

6. Discuss the 1,25(OH)₂D₃ receptor as a member of the superfamily of steroid/thyroid hormone receptors that bind to DNA.

Cholesterol

1. Characterize the relative importance of dietary cholesterol vs. biosynthesis.

2. Outline the fates of cholesterol in the body, including its role in cell membranes, as a precursor of vitamin D and steroid hormones.

2. Describe the significance of cholesterol esters formed by ACAT and LCAT

3. Discuss the importance of bile acids.

4. Describe the pathway of cholesterol biosynthesis, paying particular attention to the key intermediates: HMG-CoA, mevalonate and squalene.

5. Discuss the importance, regulation and drug inhibition of the HMG-CoA Reductase and identify the reaction catalyzed by this enzyme.

6. Describe the relevance of LDL and HDL cholesterol in the pathogenesis of atherosclerosis and indicate what dietary and drug measures can be utilized to combat this disorder.

Case Study

Identify the most likely biochemical defect responsible for familial hypercholesterolemia and what drug treatments can be used to combat the disease.

Adrenal Steroid Hormone Biosynthesis

1. Define the function, regulation and significance of the P-450scc / 20,22 lyase enzyme in converting cholesterol to pregnenolone.

2. Delineate the biosynthesis of aldosterone in the zona glomerulosa, noting the unique presence of 18-OHase and lack of 17a-OHase in these cells.

3. Describe the metabolic formation of cortisol in the zona fasciculata/reticularis, especially the key role of the 17a-OHase and the shuttling of steroids in and out of the mitochondria.

4. Delineate biochemically the body's reaction to emotional and physical stress, noting particularly the acute effects of epinephrine (glycogenolysis) and the chronic action of glucocorticoids (gluconeogenesis) and b-endorphins (analgesic).

5. Explain the biochemical action of ACTH on the zona fasciculata/reticularis cells, which mediated primarily by cAMP and secondarily by IP₃/Ca²⁺ and DAG.

Renin / Angiotensin / Aldosterone / ANP

1. Discuss the actions of aldosterone on Na⁺ retention, with special reference to the biochemical mechanism of the stimulation of Na⁺ reabsorption in the distal convoluted tubules.

2. Interrelate angiotensinogen, angiotensin I and angiotensin II at the chemical level and define the role of the proteolytic enzymes, renin and ACE.

3. Distinguish that angiotensin II stimulates aldosterone biosynthesis in the ZG by raising intracellular calcium, and ANP lowers aldosterone by reducing intracellular calcium.

4. Explain the chemistry and control of ANP secretion and its many actions including the way it links the heart, kidneys, adrenals and blood vessels.

5. Describe the mechanism of ANP action via a receptor with intrinsic guanylate cyclase activity, cGMP, second messenger and G-Kinase mediated events leading to intracellular calcium lowering.

© Dr. Noel Sturm 2004