Describe the biosynthesis of T3, T4, and epinephrine in detail.

The biosynthesis of T3 (triiodothyronine) and T4 (thyroxine) begins in the thyroid gland. The first step in the process is the uptake of iodide from the bloodstream by the thyroid follicular cells. This iodide is then transported into the follicular lumen by the sodium-iodide symporter (NIS) located on the apical membrane of the follicular cells.

Once inside the follicular lumen, the iodide is oxidized to iodine by the enzyme thyroid peroxidase (TPO). The iodine is then attached to the amino acid tyrosine, which is present in the thyroglobulin protein. This process results in the formation of monoiodotyrosine (MIT) and diiodotyrosine (DIT).

Next, two molecules of DIT combine to form T4, while one molecule of MIT and one molecule of DIT combine to form T3. These thyroid hormones are stored in the colloid of the thyroid follicles until they are needed.

When the body requires thyroid hormones, the thyroglobulin protein is taken up by the follicular cells and broken down by lysosomal enzymes. This releases T3 and T4 into the bloodstream, where they can bind to thyroid hormone-binding proteins and be transported to target tissues.

The biosynthesis of epinephrine begins in the adrenal medulla. The precursor molecule for epinephrine is the amino acid tyrosine, which is converted to L-dopa by the enzyme tyrosine hydroxylase. L-dopa is then converted to dopamine by the enzyme aromatic L-amino acid decarboxylase.

Dopamine is further converted to norepinephrine by the enzyme dopamine beta-hydroxylase. Finally, norepinephrine is converted to epinephrine by the enzyme phenylethanolamine N-methyltransferase (PNMT).

Epinephrine is released into the bloodstream in response to stress or danger and acts on various target tissues to increase heart rate, dilate airways, and mobilize energy stores.

Biosynthesis of Thyroid Hormones (T3 and T4)

1. Iodide Uptake:
- Iodide ions (I-) are actively transported into follicular cells of the thyroid gland against a concentration gradient.
- The sodium-iodide symporter (NIS) facilitates this uptake.

2. Oxidation and Organification:
- Iodide is oxidized to iodine (I2) by thyroid peroxidase (TPO).
- I2 is then incorporated into tyrosine residues on the protein thyroglobulin (Tg) to form monoiodotyrosine (MIT) and diiodotyrosine (DIT).

3. Coupling:
- MIT and DIT undergo further oxidation and condensation, catalyzed by TPO, to form triiodothyronine (T3) and thyroxine (T4).
- T3 has three iodine atoms, while T4 has four iodine atoms.

4. Storage:
- T3 and T4 are stored within the follicular lumen bound to thyroglobulin.

5. Release:
- When stimulated by thyroid-stimulating hormone (TSH), follicular cells endocytose thyroglobulin.
- Proteases cleave T3 and T4 from thyroglobulin, releasing them into the bloodstream.

Biosynthesis of Epinephrine (Adrenaline)

1. Tyrosine Hydroxylation:
- The amino acid tyrosine is hydroxylated to form L-dihydroxyphenylalanine (L-DOPA) by tyrosine hydroxylase (TH).

2. Decarboxylation:
- L-DOPA is decarboxylated by L-aromatic amino acid decarboxylase (L-AADC) to form dopamine.

3. N-Methylation:
- Dopamine is N-methylated by phenylethanolamine N-methyltransferase (PNMT) to form norepinephrine (noradrenaline).

4. Addition of a Methyl Group:
- Norepinephrine is methylated on its carbon atom by dopamine beta-hydroxylase (DBH) to form epinephrine.

Regulation of Epinephrine Synthesis:

Epinephrine synthesis is regulated by the sympathetic nervous system and stress hormones:

- Sympathetic nerve stimulation activates adenylyl cyclase, which increases cAMP levels.
- cAMP activates protein kinase A (PKA), which phosphorylates and activates TH and PNMT.
- Stress hormones, such as cortisol and vasopressin, also increase cAMP levels and stimulate epinephrine synthesis.