Biochemistry Objectives 51 - University of Arizona



Biochemistry Objectives 51

1. Oxytocin:

a. Neurophysin I: preprooxytocin has a signal peptide, oxytocin, and neurophysin I encoded in the same gene product. After processing, and cleaveage, oxytocin is freed, as is neurophysin I.

b. Mammary and uterine effects: oxytocin works via Gq protein coupled receptors in both mammary and uterine tissue. It is hypothesized that labor is induced by estrogen inducing a sharp rise in uterine Gq protein coupled receptors in uterine tissue.

c. CNS effect: oxytocin release causes maternal activity in the mother

d. Neuromodulator role coordination with systemic function: oxytocin induces labor and milk ejection which are consistent with its CNS functional increase in maternal behavior

2. Prolactin vs. GH:

a. Chemistry: prolactin and GH have 40% sequence similarity, similar lengths, and both contain two disulfide bridges

b. Cell surface receptors: prolactin and GH both bind to JAK receptors

c. Signal transduction mechanism: since both use the JAK-STAT pathway, both bind to a JAK2 receptor that recruits a TYR2 receptor to form a dimer. The monomers of the dimer then phosphorylate opposing residues, and induce STAT gene transcriptional activity.

3. Relationships between:

a. Prolactin/dopamine release from hypothalamus: dopamine release from the hypothalamus inhibits prolactin release via a Gi protein coupled receptor

b. Prolactin/GnRH release from hypothalamus: GnRH release induces formation of the sex steroids, and E2 then induces the lactotrope to release prolactin

c. Prolactin/estrogen synthesis and release: prolactin inhibits GnRH release, and therefore inhibits the synthesis and release of estrogen

d. Prolactin/E3 action in breast: E3 is derived in pregnancy, and inhibits the lactotrophic effects of prolactin while leaving the mammotrophic effects of prolactin uninhibited.

4. Prolactinomas: a benign pituitary lactotrophic tumor that causes the increased release of prolactin

Bromocryptine therapy: bromocryptine is a long acting dopamine receptor agonist that acts to tonically inhibit the lactotroph for a long period of time

5. Lactose biosynthesis in breast alveolar cell: prolactin induces lactose synthase (α-lactalbumin (prolactin induced) and galactosyl transferase (cortisol induced) which activates the conversion of UDP-galactose and glucose to lactose and free UDP.

• Note: lactose is important in the infant because it supplies calories in milk, glucose for use in the brain, galactose for glycolipid synthesis, increases Ca2+ absorption, and osmotically increases water absorption.

6. Endogenous fatty acid/TAG generation in breast alveolar cell: fatty acids are made by acetyl CoA via acetyl CoA carboxylase, fatty acid synthase, and thioesterase II. This makes medium chain fatty acids which are then incorporated into triacylglycerol molecules for release into breast milk.

7. Pathways whereby biochemical components are transferred into milk:

a. Exocytosis: amino acids increase protein synthesis of milk lipase, lactoferrin, and casein, while glucose is converted to galactose and lactose and released with the proteins.

b. Milk-fat globule pathway: triacylglycerols from chylomicrons and VLDL are absorbed to make long chain fatty acids, while thioesterase II converts acetyl-CoA into medium chain fatty acids. These free fatty acids form triacylglycerols and are secreted as TAG rich milk fat globules.

c. Transcellular pathway: sIgA is pinocytosed and then exocytosed to release immunoglobin molecules into milk

d. Paracellular pathway: immune cells and plasma proteins bypass the cell and add directly to milk

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