Question

1)Which of the following will be expected to be activated during times of prolonged starvation? (select all correct answers)

Gluconeogenesis in kidney

Lipogenesis in liver

Ketogenesis in liver

Lipolysis in adipose

Glycogenesis in muscle

Ketone utilization in brain

2)Which of the following is a description of re-purposing drugs for treatment of inborn errors of metabolism? (select one)

Use of an antisense oligonucleotide such as mipomersen that inhibits production of a toxic protein

Using proteostatis regulators to increase the production of molecular chaperons in the patient

Using drugs such as sodium benzoate to treat hyperammonemia from urea cycle disorders because they increase urinary excretion of ammonia by binding glycine and glutamine

Using a drug such as Ataluren that allows the ribosome to read-through a nonsense mutation and allow synthesis of a protein product that performs some of the necessary functions.

Using pharmacological molecular chaperone therapy to prevent misfolding of target enzymes

3)Which of the following is a proposed therapy that would prevent expression of damaged or overexpressed proteins associated with the inborn error?

Using proteostatis regulators to increase the production of molecular chaperones in the patient.

Using a drug such as Ataluren that allows the ribosome to read-through nonsense mutation and allows synthesis of a protein product that performs some of the necessary functions.

Using drugs such as sodium benzoate to treat hyperammonemia from the urea cycle disorders because they increase urinary excretion of ammonia by binding glycine and glutamine

Use of RNA interference

Using pharmacological molecular chaperone therapy to prevent misfolding of target enzymes.

Answer 1

1. During prolonged starvation, the primary subtrate for energy, glycogen/glucose is already past the bare minimum amount. Metabolic changes begin to take place in the body. The lipid stored in the adipose tissue as a reserve starts breaking down into glycerol and fatty acids i.e Lipolysis in adipose tissue.
The Liver starts producing an alternate subtrate for the brain from the fatty acid metabolism products i.e Ketogenesis in liver. As the ketone bodies can pass through the blood brain barrier, it is utilised by the brain as an alternate to glucose. i.e. Ketone utilisation in brain.

2. Drug re purposing is an economically inclined strategy to determine an already aprroved drug's potential use in treating other disease. As the drug has already passed through approvals and trials, it saves both time and money for finding suitable treatment for a disease.
Sodium Benzoate is a re purposed drug. It is now being used to treat hyperammonemia from urea cycle disorders. It is a widely used food and medicine preservative.

3.Protien misfolding is associated with a number of genetic errors in metabolism.
Molecular Chaperones are a class of highly stable protiens that assist in conformational control of other protiens. Using pharmacological molecular chaperons as protien regulators is a proposed therapy to bring about proteostatis. They enhance the folding efficiency and can detect the native/ non native state of a protiens.