Enzymes I: General Properties, Kinetics, and Inhibition
C ytid in e d ip h o sp h a te
(CDP) is a carrier of
phosphorylcholine, diacylglycerols, and other
molecules during phospholipid synthesis.
U ridin e d ip h o sp h a te
(UDP) is a carrier of
monosaccharides and their derivatives in a variety
of reactions (see bilirubin, lactose, galactose and
mannose metabolism, glycogen synthesis, and
other pathways).
P h o sp h o a d e n o sin e p h o sp h o su lfa te
“active sulfate”) is a sulfate donor in the synthesis
of sulfur-containing mucopolysaccharides as well
as in the detoxification of sterols, steroids, and
other compounds (see metabolism of the
sulfur-containing amino acids in Chapter 17).
PAPS is derived from ATP and inorganic
S -A d en o sylm eth io n in e
(SAM, “active
methionine”) is a methyl group donor in
biosynthetic reactions. It is formed from ATP and
the essential amino acid methionine.
H em e
proteins, containing the iron-protoporphyrin
group, participate in oxygen transport
(hemoglobin), oxygen storage (myoglobin),
electron transport (cytochromes), hydrogen
peroxide inactivation (catalase, peroxidase),
hydroxylases, oxygenases, and other processes.
5. Metal cofactors.
M g 2+
is required by most enzymes that use ATP.
The active form of ATP is a Mg
C a 2+
is involved in a wide variety of processes,
notably muscle contraction, blood clotting, nerve
impulse transmission, and cAMP-mediated
F e2+/F e3+ (ferro u s/ferric iro n
) is required as
heme (see above) or nonheme iron in the
functioning of many proteins.
C u + /C u 2+ {cu prou s!cu pric co p p er).
oxidase in mitochondrial electron transport
contains Fe and Cu. Tyrosinase and lysyl oxidase
also require Cu. Superoxide dismutase contains
both Cu and Zn.
e. Zn2+
{zinc io n )
is used by lactic acid
dehydrogenases, alcohol dehydrogenases, carbonic
anhydrase, carboxypeptidase A, DNA polymerase,
superoxide dismutase, and others.
M o 6+ {m olybden u m io n ).
Xanthine oxidase
contains Mo and Fe.
M n 2+ {m an gan ou s io n )
is required by acetyl-CoA
carboxylase, deoxyribonuclease (Mg2+ can
replace Mn2+ in this case), arginase, and other
S e {selen iu m )
is required for the functioning of
glutathione peroxidase.
Metal cofactors in enzymes may be bound reversibly or
firmly. Reversible binding occurs in metal-activated en-
zymes (e.g., many phosphotransferases); firm (or tight)
binding occurs in metalloenzymes (e.g., carboxypeptidase
A). Metals participate in enzyme catalysis in a number of
different ways. An inherent catalytic property of a metal
ion may be augmented by the enzyme protein, or metal
ions may form complexes with the substrate and the ac-
tive center of the enzyme and promote catalysis, or metal
ions may function in electron transport reactions between
substrates and enzymes.
Supplemental Readings and References
J. Brent, K. McMartin, S. Phillips, et al.: Fomepizole for the treatment of
ethylene glycol poisoning.
N ew E n g la n d J o u rn a l o f M ed ic in e
340, 832,
K. K. Burkhart and K. W. Kulig: The other alcohols. Methanol, ethylene
glycol, and isopropanol.
E m erg en cy M ed icin e C lin ics o f N o rth A m erica
8,913 (1990).
W. D. N. Chin, R. Barnett, and G. Sheehan: Methanol poisoning.
In ten sive
C are M ed icin e
18, 391 (1992).
C. Flexner: HIV-protease inhibitors,
N ew E n g la n d J o u rn a l o f M ed icin e
1281 (1998).
HIV-1 protease inhibitors: A review for clinicians.
J o u rn a l o f A m erica n
M ed ica l A sso cia tio n
277, 145 (1997).
G. V. Sherbet and M. S. Lakshmi:
T he G en etics o f C a n cer,
Academic Press,
San Diego (1997).
P. Houeto, J. R. Hofman, M. Imbert, P. Levillain, and F. J. Baud: Relation of
blood cyanide to plasma cyanocobalamin concentration after a fixed dose
of hydroxycolalamin in cyanide poisoning.
L a n c e t
346,605 (1995).
D. Jacobsen: The treatment for ethylene glycol poisoning.
N ew E n g la n d
J o u rn a l o f M ed icin e.
340, 879 (1999).
H. A. James and I. Gibson: The therapeutic potential of ribozymes,
B lo o d
91, 371 (1998).
J. A. Kruse and P. Cadnapapnomchai. The serum osmole gap.
Jo u rn a l o f
C lin ica l C are 9 ,
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