CYTOCHROME c OX IDASE 429
chrome c will tend toward the Fe(III) state, and programmed cell death will
proceed. The authors propose that the oxidation state of cytochrome c may
be a key regulator of apoptosis.
7.7.4.1 Cytochrome c Folding,
The preceding discussion of cytochromes c provides most detail on eukaryotic,
mitchondrial cytochromes c, a small subset of this huge superfamily. Addition-
ally, all the cytochromes c discussed in this section envelop one heme cofactor,
although many cytochromes in nature contain more than one heme cofactor.
Many other redox proteins contain a cytochrome c domain — a few of these
mentioned here include the cytochrome bc 1 complex discussed in Section 7.6,
cytochrome c oxidase to be discussed in Section 7.8, and cytochrome c peroxi-
dase, discussed briefl y in Section 7.7 (see especially Section 7.7.4.2 ).
Cytochrome c folding and electron transfer are related topics. An improp-
erly folded protein — engendered through amino acid mutation for instance —
will exhibit diminished or nonexistent electron transfer. More reports will be
forthcoming from many research groups on the topics of protein folding and
electron transfer between proteins. The reader should consult the literature
for updates on these related hot topics. The reader is referred to the 2006
Chemical Reviews article from the Bertini group (reference 101 ), which
exhaustively surveys the cytochrome c fi eld.
7.7.5 Cytochrome c Conclusions,
7.8.1 Introduction,
Cytochrome c and ubiquinol oxidases are part of an enzyme superfamily cou-
pling oxidation of ferrocytochrome c (in eukaryotes) and ubiquinol (in pro-
karyotes) to the 4 e − /4 H + reduction of molecular oxygen to H 2 O. After this
introduction, we will concentrate on the cytochrome c oxidase enzyme. The
two enzymes, cytochrome c oxidase (CcO) and ubiquinol oxidase, are usually
defi ned by two criteria: (1) The largest protein subunit (subunit I) possesses a
high degree of primary sequence similarity across many species; (2) members
possess a unique bimetallic center composed of a high - spin Fe(II)/(III) heme
in close proximity to a copper ion. Cytochrome c oxidase (CcO) is the terminal
Figure 7.37 Glutathione.
HN CH C
CH 2
NH
O
SH
C CH 2
O
+H 3 N HC H 2 C H 2 C
CO 2 -
glutathione (γ-glutamylcysteinylglycine)
