CASE FILES: BIOCHEMISTRY
B IO C H E M IS T R Y PE A R L S
The eukaryote cell cycle is composed of the following four phases:
M phase, mitosis; G1
phase (gap 1), between mitosis and initia-
tion of DNA synthesis; S phase, DNA synthesis; and G2 phase
(gap 2), cell growth and macromolecule synthesis.
The cells in G0 are in a nonproliferative or quiescent state that can
vary tremendously in length.
DNA synthesis requires the formation of dTMP and the purines ade-
nine and guanine. THF, derived from the vitamin folic acid, is
required for the biosynthesis of these nucleotides.
The cell cycle is regulated by specific proteins: CDKs, which are
serine/threonine protein kinases, and the cyclins, which are regu-
latory proteins that bind to the CDKs.
Treatment with methotrexate blocks the cell’s ability to regenerate
THF, leading to inhibition of these biosynthetic pathways. Thus
methotrexate affects DNA synthesis.
Alberts B, Johnson A, Lew J, et al. The cell cycle and programmed cell death. In:
Molecular Biology of the Cell, 4th ed. New York: Garland, 2002.
Cory JG. Purine and pyrimidine nucleotide metabolism. In: Devlin TM, ed. Textbook
of Biochemistry with Clinical Correlations, 5th ed. New York: Wiley-Liss, 2002.