The enzyme dihydrofolate reductase (DHFR) normally resides in the cytosol, and it can be imported into mitochondria by appending a mitochondrial signal sequence. However, when this modified DHFR is incubated with methotrexate, which is a substrate analog that binds tightly to the active site, the modified DHFR is no longer imported. Propose an explanation for this finding.

Why do the cytochrome electron-transfer processes have different standard reduction potentials, despite the fact that they all utilize the identical iron oxidation–reduction reaction?

Assume that the gene for pyruvate dehydrogenase kinase is mutated and the mutatedenzyme remain active in the presence or absence of upstream regulatory signals. Patients withsuch a gene mutation exhibit all the symptoms of beriberi. Do you think beriberi, resulting fromsuch mutations of pyruvate dehydrogenase kinase, can be successfully treated by placing suchpatients on a thiamine-enriched diet? Briefly explain your reasonings.

Only 37 of the proteins in mitochondria are encoded by the mitochondrial DNA. The other proteins are encoded in nuclear DNA, then translated and transported to the mitochondria. Describe one unique feature of protein transport across mitochondrial membranes.