The enzyme dihydrofolate reductase (DHFR) normally resides in the cytosol, and DHFR 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. a) Propose an explanation for why methotrexate prevents import of DHFR into mitochondria. b) Suppose that DHFR were modified instead by appending a nuclear localization signal. Would you expect methotrexate to prevent transport of this modified DHFR into the nucleus? Why or why not?

Human Anatomy & Physiology (11th Edition)
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ISBN:9780134580999
Author:Elaine N. Marieb, Katja N. Hoehn
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Chapter1: The Human Body: An Orientation
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The enzyme dihydrofolate reductase (DHFR) normally resides in the cytosol, and
DHFR 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.
a) Propose an explanation for why methotrexate prevents import of DHFR into
mitochondria.
b) Suppose that DHFR were modified instead by appending a nuclear localization
signal. Would you expect methotrexate to prevent transport of this modified DHFR
into the nucleus? Why or why not?

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