Question

7. Individual C has a mutation in the proopiomelanocortin gene (POMC), resulting in the lack of functional alpha-melanocyte stimulating hormone (alpha-MSH).

a) How might this mutation impact binding at the MC4 receptor?

b) Phenotypically, is individual C likely to be underweight, normal weight, or overweight? Why?

Answer 1

Question 7:

a) Proopiomelanocortin (POMC) is a precursor hormone (peptide), which when cleaved, gives rise to several endogenous agonists like the alpha-MSH, beta-MSH, gamma-MSH, ACTH, etc. The alpha-MSH acts as a ligand for the MC4 receptor, regulating its various functions.

The alpha-MSH is responsible for producing the skin and hair pigment - melanin. It also acts in combination with beta-MSH to regulate the energy homeostasis, i.e., the maintenance of equilibrium between the amount of energy intake and the amount of energy spent.

The MC4 receptor regulates various other functions of the body like - glucose homeostasis, lipid homeostasis, etc.

Mutation in the POMC gene causes the production of abnormal precursor protein POMC, which does not cleave to give rise to the various endogenous hormones. As such, the deficiency of alpha-MSH and other hormones prevail. The deficiency of alpha-MSH means that the hormone will not be available to bind to its receptor - MC4 receptor.

b) As stated above, alpha-MSH in combination with beta-MSH plays an important role in energy homeostasis, i.e, the maintenance of an equilibrium of the amount of energy intake and the amount of energy spent. Mutation in the POMC gene leads to an abonormal POMC precursor which leads to deficiency of these hormones, viz. alpha-MSH and beta-MSH. The deficiency of these hormones causes abnormal regulation of the energy homeostasis so that now the equilibrium is disrupted and the person tends to overeat. Namely, the equilibrium between the amount of energy intake and the amount of energy spent is dysregulated. Overeating leads to a person being overweight and obese.