Biochemistry of Protein Hormone Synthesis and Processing

Question 1

Regulation of Hormone Secretion

Answer 1

1) Physiological Changes (e.g blood glucose regulation)
2) -ve feedback,

Question 2

3 Classes of Hormones

Answer 2

• Peptide/Proteins (Hydrophilic)
• Cholesterol Derivatives (Hydrophobic)
• Modified AAs

Question 3

Target Cell Recognition (P/P)

Answer 3

1) Hormones bind to surface receptors
2) Triggers signal transduction
3) Opens ion channel and enzyme activation

Question 4

Target Cell Recognition (Steroid etc)

Answer 4

1) Diffuse through phospholipid bilayer
2) Bind to intracellular receptor
3) Activate target molecules resulting in changes in gene expression

Question 5

P/P Hormones

Answer 5

• Water soluble
  1) Encoded by specific gene transcribed into mRNA then translated into precursor - preprohormone
  2) Signal peptide removed via endopeptidases to give prohormones (In ER) (Post-Trans Mod)
  3) Prohormones are processed into the active hormones and packaged into secretory vesicles
  4) Secretory vesicles move to plasma membrane where they await a signal. Then they are exocytosed and secreted into blood stream

In some cases the prohormone is secreted and converted in the extracellular fluid into the active hormone: an example is angiotensin is secreted by liver and converted into active form by enzymes secreted by kidney and lung

Question 6

Signal Sequences

Answer 6

• amino terminus of the prepeptide, there is a signal sequence of about 15-30 amino acids, which tells the cell to send the peptide into the cisterna of the endoplasmic reticulum
• Inside the ER, the signal sequence is cleaved off

Question 7

Types of P/P Hormone

Answer 7

Pre hormone: Signal Sequence + Mature peptide
Pre prohormone: Signal Sequence + Prohormone
Prohormone: Precursor form of peptide (inactive)

Question 8

PTM - Glycosylation

Answer 8

Addition of carbohydrates to amino acids on the peptide, utilizing specific enzymes (transferases)

• Carbohydrate side chains play roles in subunit assembly, secretion, plasma half life, receptor binding, and signal transduction
• Glycosylation begins in the RER, and is completed in the Golgi.
• N-linked sugars are bound to an asparagine residue, if the coding sequence Asn-X-Thr or Asn-X-Ser is present (X = any amino acid).
• O-linked sugars are bound to serine/threonine residues

Question 9

Other PTMs

Answer 9

Influencing their tertiary/quaternary structure and thus their biological activity
- Phosphorylated
- Sulphated
- Acetylated
- Amidated
Change the overall charge of peptide and can change solubility, stability and biological activity.

Question 10

Pituitary Gland

Answer 10

Anterior:
- Gonadotrophins, Thyrotrophins, GH, Adrenocorticotrophins, Prolactin
Intermediate:
- Melanotrophs
Posterior:
- Oxytocin, Vasopressin

Question 11

TRH Synthesis

Answer 11

1) Cleavage of peptides from precursor by PC1/2
2) Removal of dibasic via carboxypeptidase
3) Amidation and generation of pyroglutamic acid