Question

3. Cellular transport of proteins is very important in order for a cell to function properly. For each of the mutations below, (1) explain what type of transport will be affected by explaining the correct transport process and where the problem will arise and (2) where the proteins that are transported incorrectly will be found (6 pts). (1) A mutation in N-acetyl transferase, the enzyme that adds N-linked glycosylation to proteins. (2) A mutation in the TOM complex (3) A mutation that causes GTP to not be hydrolyzed in the cytosol

Answer 1

1) A mutation in N-acetyl transferase-

N-acetyltransferase (NAT) is an enzyme that catalyzes the acetyl groups transfer from acetyl Co A to arylamines. These acetyl groups are needed for conjugation of metabolites from the liver which is needed for excretion of the byproducts. This phase II metabolism of excretion is important for metabolizing and excreting drug products.

Mutation in N-acetyltransferase will inhibit acetyl groups transfer, it will affect excretion of end products of drugs increasing the liver toxicity. The problem will occur in the liver due to no detoxification.

Acetyl groups will accumulate in cells.

2) A mutation in TOM complex-

TOM stands for Translocase of Outer Membrane. It is a protein which translocates proteins encoded/formed by nuclear DNA into the mitochondria through the outer mitochondrial membrane. The proteins are required for oxidative phosphorylation.

Mutation in TOM complex will inhibit the protein transfer across the outer mitochondrial membrane ultimately mitochondrial membrane. It will affect the mitochondria functions like cytochrome c release from mitochondria. Cytochrome c release is an important event in apoptosis. So a mutation in TOM complex might affect apoptosis.

Mutation in TOM that will inhibit protein transport will lead to protein accumulation in the cytosol.

3) A mutation that causes GTP to not be hydrolyzed in the cytosol will inhibit protein transport into mitochondria. GTP hydrolysis in the cytosol is needed for protein import. Energy from GTP hydrolysis is required for unfolding the protein during transport. If GTP is not hydrolyzed, then energy will not be available for unfolding the proteins for transport through the transporters.

This will lead to accumulation of proteins in the cytosol and prevent mitochondrial functions like cytochrome c release, ATP production, citric acid cycle.