Principles of Biochemistry, Volume 2 - A. Lehninger 1985

Bioenergetics and Metabolism
Glycolysis: The Central Pathway of Glucose Catabolism
Glycolysis products still retain a significant amount of free energy

Glycolysis releases only a small fraction of the total energy stored in a glucose molecule. The overall standard free-energy change for the Complete oxidation of glucose to CO₂ and H₂O is –686 kcal/mol (Table 14–3). Consequently, the free-energy yield from the glycolytic breakdown of glucose into two molecules of lactate (∆G⁰' = -47.0 kcal/mol) accounts for only (47/686) ∐ 100 = 6.9% of the energy that can be released by the complete oxidation of glucose to CO₂ and H₂O. Most of the biologically available energy contained in the glucose molecule is retained in the products of glycolysis—two molecules of lactate. This energy can be released only if the glycolytic products undergo complete oxidation to CO₂ and H₂O by molecular oxygen, which acts as an electron acceptor (we will discuss this in detail in the next chapter). Nonetheless, this anaerobic glycolysis up to the lactate stage should by no means be considered an inefficient process that wastes energy. On the contrary, Glycolysis is a remarkably sophisticated process because it provides energy from glucose without requiring its oxidation. In animals, the lactate produced in working Muscles and diffused into the Blood can be recycled: it is transported to the Liver, where it is reconverted into glucose during the recovery period following intense muscular exertion. In some animal species, anaerobic glycolysis plays a crucial role in Muscle activity (Box 15–1).

Box 15–1. Anaerobic Glycolysis, Oxygen Debt, Alligators, and Deep-Sea Dwellers

Most vertebrates are primarily aerobic organisms; their glucose is first converted into Pyruvate via glycolysis, after which this pyruvate undergoes complete oxidation to CO₂ and H₂O driven by molecular oxygen. In most vertebrates, and particularly in humans, anaerobic glycolysis is engaged only briefly during intense muscle exertion, such as a 100-meter dash—that is, at times when oxygen cannot be delivered to Tissues quickly enough to support pyruvate oxidation and coupled ATP synthesis. Under these conditions, muscles utilize their internal Glycogen reserves as "fuel" and generate ATP through anaerobic glycolysis, with lactate as the end product. Consequently, during short-distance sprints, very significant amounts of lactate accumulate in the blood. Later, during the recovery period, this lactate is slowly converted back into glucose in the liver; throughout the recovery period, oxygen consumption gradually declines until normal Respiration rates are finally re-established. The excess oxygen consumed during the recovery period serves as a measure of the oxygen debt. This amount of oxygen is required to synthesize (via respiration) the appropriate amount of ATP needed to replenish the depleted glycogen stores in The Liver and muscles—effectively "paying off the debt" incurred by strenuous muscle activity during the run.

As an energy source for Muscle contraction, anaerobic glycolysis plays an especially vital role in white muscle fibers. Most skeletal muscles contain a mix of both white and red fibers, but some muscles consist almost entirely of either red or white fibers. In turkeys, the wing muscles are white, and these birds can fly only very short distances. In horses, which are capable of sustained, continuous running, the leg muscles consist predominantly of red fibers. White muscle fibers, which contain few Cell/35.html">Mitochondria, are characterized by an extremely high contraction frequency. Anaerobic glycolysis serves as their ATP source, allowing them to work at maximum intensity for only very short periods because their glycogen reserves are utilized inefficiently. In contrast, red muscles contract more slowly, contain numerous mitochondria, and derive their energy primarily from the oxidative METABOLISM of cellular "fuel"; therefore, they can work continuously for long periods of time.

Generally speaking, in small animals, oxygen is delivered to muscles rapidly enough by circulatory systems that there is no need for the anaerobic utilization of muscle glycogen. Birds, for example, often cover vast distances at high speeds during migration without incurring any oxygen debt. The red muscles of many medium-sized running animals also rely predominantly on aerobic metabolism. However, in large animals undergoing intense and prolonged exertion, the Circulatory system is no longer able to fully sustain aerobic metabolism in the muscles. These animals typically move slowly and are driven to intense muscular activity only by extreme circumstances, since each such burst of activity must be followed by a long recovery period necessary to repay the oxygen debt.

Alligators and other crocodilians, for instance, are sluggish and lethargic most of the time, yet these reptiles are capable of lightning-fast strikes and equally swift, dangerous sweeps of their powerful tails. Such explosive bursts of activity are brief and are invariably followed by a lengthy recovery period. When rapid movements are required, ATP is generated in the white skeletal muscles of these animals via anaerobic glycolysis. Because muscle glycogen reserves are not exceptionally large, they are quickly depleted during intense muscle work. Furthermore, very high concentrations of the anaerobic glycolysis product, lactate, accumulate in the muscles and extracellular fluid during such bursts of activity. While a trained athlete needs only about 30 minutes to recover fully after a 100-meter dash, an alligator may require many hours of resting with elevated oxygen consumption following a sudden lunge to clear the excess lactate from its blood and restore muscle glycogen levels.

Similar metabolic constraints dictate the physiological patterns of other large animals, such as elephants and rhinoceroses, as well as whales, seals, and other marine mammals that remain submerged for extended periods. In dinosaurs and other giant prehistoric creatures, anaerobic glycolysis likely served as the primary energy source for muscle work, meaning they too required prolonged recovery periods. During these times, such animals would have been easy prey for smaller, more agile predators that were better equipped to utilize oxygen and were thus far better adapted for sustained muscular activity.

Deep-sea research has revealed that at very great depths, where the dissolved oxygen content of the Water approaches zero, numerous animal species nevertheless thrive. The metabolism of these deep-sea inhabitants is predominantly anaerobic; carbohydrate breakdown leads to The formation of lactate and several other products, most of which must be excreted from the Organism. In some marine vertebrates, glucose is fermented not to lactate, but to ethanol and CO₂, to yield energy in the form of ATP.