Enzymes I: General Properties, Kinetics, and inhibition
TA B LE 6-2
Effects of Competitive Inhibitors on Km and Vmax (Michaelis-Menten Kinetic
K m( 1
+ K; y
In uncompetitive inhibition, the inhibitor binds equally well to E and ES.
reductase is competitively inhibited by methotrexate.
is needed for the synthesis of DNA precur-
sors, a deficiency causes most harm to those cells which
synthesize DNA rapidly. Certain types of cancers (e.g.,
the leukemias) exhibit an extremely high rate of cell divi-
sion and are particularly susceptible to folate antagonists.
The reactions of one-carbon metabolism are discussed in
^ C -C H 2-
(4-amino-W'°-methyl folic acid)
Allopurinol inhibits the formation of xanthine and of uric
acid, catalyzed by xanthine oxidase, and is itself trans-
formed into alloxanthine by the enzyme. Alloxanthine
bears the same structural relationship to xanthine that al-
lopurinol does to hypoxanthine:
Inhibition of Xanthine Oxidase
Uric acid, the end
product of purine catabolism in humans, is formed by
the serial oxidation of hypoxanthine and of xanthine,
catalyzed by xanthine oxidase.
Allopurinol, a structural analogue of hypoxanthine, is a
competitive inhibitor as well as a substrate for xanthine
Alloxanthine, however, remains tightly bound to the ac-
tive site of the enzyme by chelation with Mo4+. Since xan-
thine oxidase is a molybdenum-dependent enzyme whose
catalytic cycle requires the reversible oxidation and re-
duction of Mo4+ to Mo6+ (Chapter 27), the reoxidation
of Mo4+ to Mo6+ in the presence of alloxanthine is very