13.

3 Biological Oxidation-Reduction Reactions 515

O
TABLE 13–9 Some Enzymes (Flavoproteins)
C O C That Employ Flavin Nucleotide Coenzymes


  CH3 Flavin Text

Niacin Nicotine Enzyme nucleotide page(s)
(nicotinic acid)
Acyl–CoA dehydrogenase FAD XXX

O NH3 Dihydrolipoyl dehydrogenase FAD XXX
Succinate dehydrogenase FAD XXX
C CH2 CH COO
NH2 Glycerol 3-phosphate dehydrogenase FAD XXX
Thioredoxin reductase FAD XXX–XXX
  NADH dehydrogenase (Complex I) FMN XXX

Nicotinamide Tryptophan
Glycolate oxidase FMN XXX

FIGURE 13–17 Structures of niacin (nicotinic acid) and its deriva-

tive nicotinamide. The biosynthetic precursor of these compounds is
loxazine ring is produced, abbreviated FADH• and
tryptophan. In the laboratory, nicotinic acid was first produced by ox-
FMNH•. Because flavoproteins can participate in either
idation of the natural product nicotine—thus the name. Both nicotinic
acid and nicotinamide cure pellagra, but nicotine (from cigarettes or
one- or two-electron transfers, this class of proteins
elsewhere) has no curative activity. is involved in a greater diversity of reactions than the
NAD (P)-linked dehydrogenases.
Like the nicotinamide coenzymes (Fig. 13–15), the
reduced, and whose caloric needs are often met with dis-
flavin nucleotides undergo a shift in a major absorption
tilled spirits that are virtually devoid of vitamins, in-
band on reduction. Flavoproteins that are fully reduced
cluding niacin. In a few places, including the Deccan
(two electrons accepted) generally have an absorption
Plateau in India, pellagra still occurs, especially among
maximum near 360 nm. When partially reduced (one
the poor. ■
electron), they acquire another absorption maximum at
about 450 nm; when fully oxidized, the flavin has max-
Flavin Nucleotides Are Tightly Bound in Flavoproteins
ima at 370 and 440 nm. The intermediate radical form,
Flavoproteins (Table 13–9) are enzymes that catalyze reduced by one electron, has absorption maxima at 380,
oxidation-reduction reactions using either flavin 480, 580, and 625 nm. These changes can be used to as-
mononucleotide (FMN) or flavin adenine dinucleotide say reactions involving a flavoprotein.
(FAD) as coenzyme (Fig. 13–18). These coenzymes, the The flavin nucleotide in most flavoproteins is bound
flavin nucleotides, are derived from the vitamin ri- rather tightly to the protein, and in some enzymes, such
boflavin. The fused ring structure of flavin nucleotides as succinate dehydrogenase, it is bound covalently. Such
(the isoalloxazine ring) undergoes reversible reduction, tightly bound coenzymes are properly called prosthetic
accepting either one or two electrons in the form of one groups. They do not transfer electrons by diffusing from
or two hydrogen atoms (each atom an electron plus a one enzyme to another; rather, they provide a means by
proton) from a reduced substrate. The fully reduced which the flavoprotein can temporarily hold electrons
forms are abbreviated FADH2 and FMNH2. When a fully while it catalyzes electron transfer from a reduced sub-
oxidized flavin nucleotide accepts only one electron strate to an electron acceptor. One important feature of
(one hydrogen atom), the semiquinone form of the isoal- the flavoproteins is the variability in the standard re-
duction potential (E
) of the
bound flavin nucleotide. Tight as-
sociation between the enzyme and
prosthetic group confers on the
flavin ring a reduction potential
typical of that particular flavopro-
tein, sometimes quite different
from the reduction potential of the
free flavin nucleotide. FAD bound
to succinate dehydrogenase, for
example, has an E
close to 0.0 V,
compared with 0.219 V for free
Frank Strong, D. Wayne Woolley, Conrad Elvehjem, FAD; E
for other flavoproteins
1908–1993 1914–1966 1901–1962 ranges from 0.40 V to 0.06 V.
516 Chapter 13 Principles of Bioenergetics

isoalloxazine ring
O H O H O

CH3 N H e  CH3 N 
H e 
CH3 N
NH • NH NH

CH3 N N O CH3 N N O CH3 N N O

CH2 R R H
HCOH FADH• (FMNH•) FADH2 (FMNH2)
FMN (semiquinone) (fully reduced)
HCOH
HCOH
CH2
FAD
O

O P O
O
NH2

O P O N
N
O
N N
CH2 O
FIGURE 13–18 Structures of oxidized and reduced FAD and FMN.
H H FMN consists of the structure above the dashed line on the FAD (ox-
H H
idized form). The flavin nucleotides accept two hydrogen atoms (two
OH OH electrons and two protons), both of which appear in the flavin ring
Flavin adenine dinucleotide (FAD) and system. When FAD or FMN accepts only one hydrogen atom, the semi-
flavin mononucleotide (FMN) quinone, a stable free radical, forms.

Flavoproteins are often very complex; some have, in ad- ■ Biological oxidation-reduction reactions can be
dition to a flavin nucleotide, tightly bound inorganic ions described in terms of two half-reactions, each
(iron or molybdenum, for example) capable of partici- with a characteristic standard reduction
pating in electron transfers. potential, E
.
Certain flavoproteins act in a quite different role as ■ When two electrochemical half-cells, each
light receptors. Cryptochromes are a family of flavo- containing the components of a half-reaction,
proteins, widely distributed in the eukaryotic phyla, that are connected, electrons tend to flow to the
mediate the effects of blue light on plant development half-cell with the higher reduction potential.
and the effects of light on mammalian circadian rhythms The strength of this tendency is proportional
(oscillations in physiology and biochemistry, with a to the difference between the two reduction
24-hour period). The cryptochromes are homologs of potentials (E) and is a function of the
another family of flavoproteins, the photolyases. Found concentrations of oxidized and reduced
in both prokaryotes and eukaryotes, photolyases use species.
the energy of absorbed light to repair chemical defects
in DNA. ■ The standard free-energy change for an
We examine the function of flavoproteins as elec- oxidation-reduction reaction is directly
tron carriers in Chapter 19, when we consider their roles proportional to the difference in standard
in oxidative phosphorylation (in mitochondria) and pho- reduction potentials of the two half-cells:
tophosphorylation (in chloroplasts), and we describe G
 n E
.
the photolyase reactions in Chapter 25. ■ Many biological oxidation reactions are
dehydrogenations in which one or two
SUMMARY 13.3 Biological Oxidation-Reduction hydrogen atoms (H  e) are transferred
Reactions from a substrate to a hydrogen acceptor.
Oxidation-reduction reactions in living cells
■ In many organisms, a central energy-conserving involve specialized electron carriers.
process is the stepwise oxidation of glucose to ■ NAD and NADP are the freely diffusible
CO2, in which some of the energy of oxidation is coenzymes of many dehydrogenases. Both
conserved in ATP as electrons are passed to O2. NAD and NADP accept two electrons and