Under anaerobic conditions, glucose and other 6-carbon sugars are fi rst converted stepwise to a pair of 3-carbon pyruvic acid molecules during glycolysis, described on page 64 (see also Figure 4.11 ). This series of reactions yields two molecules of ATP and two molecules of NADH. In the absence of molecular oxygen, further oxidation of pyruvic acid cannot occur because without oxygen as the fi nal electron acceptor in the electron transport chain, the Krebs cycle and electron transport chain cannot operate and cannot, therefore, reoxidize the NADH pro-duced in glycolysis. The problem is neatly solved in most animal
hic70049_ch04_058-074.indd 67
hic70049_ch04_058-074.indd 67 7/23/07 2:18:25 PM7/23/07 2:18:25 PM
cells by reducing pyruvic acid to lactic acid ( Figure 4.16 ). Pyru-vic acid becomes the fi nal electron acceptor and lactic acid the end product of anaerobic glycolysis. This step converts NADH to NAD ⫹ , effectively freeing it to recycle and pick up more H ⫹ and electrons. In alcoholic fermentation (as in yeast, for example) the steps are identical to glycolysis down to pyruvic acid. One of its carbons is then released as carbon dioxide, and the resulting 2-carbon compound is reduced to ethanol, thus regenerating the NAD ⫹ .
Anaerobic glycolysis is only one-eighteenth as efficient as complete oxidation of glucose to carbon dioxide and water, but its key virtue is that it provides some high-energy phosphate in situations in which oxygen is absent or in short supply. Many microorganisms live in places where oxygen is severely depleted, such as waterlogged soil, in mud of a lake or sea bottom, or within a decaying carcass. Vertebrate skeletal muscle may rely heavily on glycolysis during short
Figure 4.14
Oxidative phosphorylation. Most of the ATP in living organisms is produced in the electron transport chain. Electrons removed from fuel molecules in cellular oxidations (glycolysis and the Krebs cycle) fl ow through the electron transport chain, the major components of which are four transmembrane protein complexes (I, II, III, and IV). Electron energy is tapped by the major complexes and used to push H⫹ outward across the inner mitochondrial membrane. The H⫹ gradient created drives H⫹ inward through proton channels (ATP synthase) that couple H⫹ movement to ATP synthesis.
Downhill movement of H+ through proton channel is coupled to ATP synthesis Outer membrane
of mitochondrion
Inner membrane of mitochondrion
H+ 2 H+ + H+
H+ H+
I II III IV
ADP + Pi
H2O
CO2
O2
CO2 Electron transport
coupled to H+ transport across membrane
GLYCOLYSIS Glucose
Pyruvic acid
Acetyl-CoA CoA
NADH NADH FADH2
e-2 e- + O
Krebs cycle
ATP
ATP
MATRIX
T A B L E 4 . 1
Calculation of Total ATP Molecules Generated in Respiration
ATP Generated Source
4 Directly in glycolysis
2 As GTP (→ATP) in Krebs cycle
4 From NADH in glycolysis
6 From NADH produced in pyruvic acid to acetyl-CoA reaction
4 From reduced FAD in Krebs cycle
18 From NADH produced in Krebs cycle
38 Total
−2 Used in priming reactions in glycolysis 36 Net
hic70049_ch04_058-074.indd 68
hic70049_ch04_058-074.indd 68 7/23/07 2:18:26 PM7/23/07 2:18:26 PM
w w w . m h h e . c o m / h i c k m a n i p z 1 4 e CHAPTER 4 Cellular Metabolism 69
Figure 4.15
Pathway for oxidation of glucose and other carbohydrates. Glucose is degraded to pyruvic acid by cytoplasmic enzymes (glycolytic pathway). Acetyl-CoA is formed from pyruvic acid and is fed into the Krebs cycle. An acetyl-CoA molecule (two carbons) is oxidized to two molecules of carbon dioxide with each turn of the cycle. Pairs of electrons are removed from the carbon skeleton of the substrate at several points in the pathway and are carried by oxidizing agents NADH or FADH2 to the electron transport chain where 32 molecules of ATP are generated. Four molecules of ATP are also generated by substrate phosphorylation in the glycolytic pathway, and two molecules of ATP (initially GTP) are formed in the Krebs cycle. This yields a total of 38 molecules of ATP (36 molecules net) per glucose molecule. Molecular oxygen is involved only at the very end of the pathway as the fi nal electron acceptor at the end of the electron transport chain to yield water.
ADP ATP
ADP ATP
Krebs cycle 2 FADH2
Fructose, other hexoses
Glucose
Glucose-6-phosphate
2 ATP
2 ATP
2 ATP
2 ADP 2 ADP
Fructose-1,6-bisphosphate
Triose phosphate
Triose phosphate
Pyruvic acid
Pyruvic acid
Acetyl-CoA Acetyl-CoA Glycogen
Plasma membrane
Mitochondrial membranes 6 O2
32 ATP
Electron transport chain 6 H2O 2 CO2
2 CO2 CO2 CO2
Krebs cycle (2 turns)
NADH
NADH NADH
NADH
Electron transport chain Krebs cycle Mobilization
of acetyl-CoA
Glycolysis
CYTOSOL
MATRIX 2 NADH
2 NADH
2 NADH
hic70049_ch04_058-074.indd 69
hic70049_ch04_058-074.indd 69 7/23/07 2:18:31 PM7/23/07 2:18:31 PM
bursts of activity when contraction is so rapid and powerful that oxygen delivery to tissues cannot supply energy demands by oxidative phosphorylation alone. At such times an animal has no choice but to supplement oxidative phosphorylation with anaerobic glycolysis. One kind of muscle fi ber (white muscle) has few mitochondria and primarily uses anaerobic glycolysis for ATP production (see Chapter 29, p. 661). In all muscle types, intense or strenuous activity is followed by a period of increased oxygen consumption as lactic acid, the end product of anaerobic glycolysis, diffuses from muscle to the liver where it is metabolized. Because oxygen consumption increases following heavy activity, the animal is said to have acquired an oxygen debt during such activity, which is repaid when activity ceases, and accumulated lactic acid is metabolized.
Some animals rely heavily on anaerobic glycolysis during normal activities. For example, diving birds and mammals use glycolysis almost entirely to give them the energy needed to sustain long dives without breathing (that is, without requiring oxygen). Salmon would never reach their spawning grounds were it not for anaerobic glycolysis providing almost all of the ATP used in the powerful muscular bursts needed to carry them up rapids and falls. Many parasitic animals have dis-pensed with oxidative phosphorylation entirely at some stages of their life cycles. They secrete relatively reduced end prod-ucts of their energy metabolism, such as succinic acid, acetic acid, and propionic acid. These compounds are produced in mitochondrial reactions that derive several more molecules of ATP than does the path from glycolysis to lactic acid, although such sequences are still far less effi cient than the aerobic elec-tron transport chain.