Cell Metabolism - Bioprocess Engineering: Kinetics, Biosystems, Sustainability and Reactor Design - page 530

that is formed directly from pyruvate serves as an entry point to the TCA cycle. In yeast,
the primary metabolic product is ethanol, but even with respiratory growth, where
complete reoxidation of NADH is possible by oxidative phosphorylation the pyruvate
dehydrogenase complex ( Fig. 10.28 c), which catalyzes the direct conversion of pyruvate
to acetyl-CoA, may be by-passed as indicated. Above a certain glucose uptake rate, the
respiratory capacity becomes limiting and this leads to overflow in the by-pass and conse-
quently ethanol is formed. This overflow metabolism is traditionally referred to as the
Crabtree effect.
Acetyl-CoA can be regarded as an activated form of acetic acid as it can be converted to
acetic acid in Fig. 10.28 a and b. As seen in the last step of acetic acid formation an ATP is
released, hereby doubling the ATP yield by catabolism of glucose from 2 to 4 ATP per glucose
molecule. This is the reason why bacteria use the mixed acid pathways at very low glucose
fluxes. To obtain a complete regeneration of NAD þ , the flow of carbon to the metabolic end
products formic acid, ethanol and acetic acid must, however, be balanced.
Finally, it should be noted that the pathways shown in Fig. 10.28 are of necessity quite
simplified. Thus, in E. coli succinate may be an end product. Furthermore, in some
bacteria, alternative pathways from pyruvate to other end products such as butanol
(together with butyric acid and acetone) or to 2,3-butanediol (together with acetoin)
may be active.

10.7.5. Respiration
The respiration reaction sequence is also known as the electron transport chain. The
process of forming ATP from the electron transport chain is known as oxidative phosphoryla-
tion. Electrons carried by NADH H þ and FADH 2 are transferred to oxygen via a series of

electron carriers, and ATPs are formed. Three ATPs are formed from each NADH

þ

H þ
and two ATPs for each FADH 2 in eukaryotes. The details of the respiratory (cytochrome)
chain are depicted in Fig. 10.29 . The major role of the electron transport chain is to regenerate
NADs for glycolysis and ATPs for biosynthesis. The term P/O ratio is used to indicate the
number of phosphate bonds made (ADP

þ

þ H 3 PO 4 / ATP) for each oxygen atom used as

an electron acceptor.
The cytochromes (cytochrome a and cytochrome b) and the coenzyme ubiquinone CoQ n
are positioned at or near the cytoplasmic membrane (or the inner mitochondrial
membrane in eukaryotes), and when electrons pass through the respiratory chain protons
are pumped across the membrane (in prokaryotes it is the cytosolic membrane and in
eukaryotes it is the inner mitochondrial membrane). When the protons reenter the cell
(or the mitochondria) through the action of the enzyme F 0 F 1 -ATPase, as shown in
Fig. 10.29 , ADP may be phosphorylated to form ATP, and the respiratory chain is therefore
often referred to as oxidative phosphorylation. The number of sites where protons are
pumped across the membrane in the respiratory chain depends on the organism. In
many organisms, there are three sites, and here ideally three moles of ATP can be formed
by the oxidation of NADH. FADH 2 enters the respiratory chain at CoQ n . The electrons
therefore do not pass the NADH dehydrogenase and the oxidation of FADH 2 therefore
results only in the pumping of protons across the membrane at two sites. The number
of moles of ATP formed for each oxygen atom used in the oxidative phosphorylation is