Glycolysis Pathway

Carbohydrates are the first cellular constituents formed by photosynthetic organisms and result from the fixation of CO2 on the absorption of light. The carbohydrates are metabolized to yield a vast array of other organic compounds, many of which are subsequently utilized as dietary constituents by animals. The animals ingest great quantities of carbohydrates that can be either stored, or oxidized to obtain energy as ATP, or converted to lipids for more efficient energy storage or used for the synthesis of many cellular constituents.

The major function of carbohydrates in metabolism is as a fuel to be oxidized and provide energy for other metabolic processes. The carbohydrate is utilized by cells mainly as glucose. The 3 principal monosaccharides resulting from digestive processes are glucose, fructose, and galactose. Much of the glucose is derived from starch which accounts for over half of the fuel in the diets of most humans. Glucose is also produced from other dietary components by the liver and, to a lesser extent, by the kidneys. Fructose results in a large intake of sucrose while galactose is produced when lactose is the principal carbohydrate of the diet. Both fructose and galactose are easily converted to glucose by the liver. It is thus apparent that glucose is the major fuel of most organisms and that it can be quickly metabolized from glycogen stores when there arises a sudden need for energy. Pentose sugars such as arabinose, ribose and xylose may be present in the diet. But their fate after absorption is, however, obscure.

Glycolysis (glycosG = sugar (sweet); lysis = dissolution) is the sequence of 10 enzyme-catalyzed reactions that convert glucose into pyruvate with the simultaneous production of ATP. Moreover, glycolysis also includes the formation of lactate from pyruvate. The glycolytic sequence of reactions differs from one species to the other only in the mechanism of its regulation and in the subsequent metabolic fate of the pyruvate formed. In aerobic organisms, glycolysis is the prelude to the citric acid cycle and the electron transport chain which together harvest most of the energy contained in glucose. In fact, glycolysis is the central pathway of glucose catabolism

Glycolysis takes place in the extramitochondrial part of the cell (or the soluble cytoplasm). It is frequently referred to as Embden-Meyerhof-Parnas or EMP pathway, in honour of these pioneer workers in the field, and still represents one of the greatest achievements in the field of biochemistry. Other illustrious investigators, who contributed significantly to the final elucidation of the glycolytic pathway, include Fritz A. Lipmann, Harden and Young, A.V. Hill, Carl Neuberg, Otto Warburg, and Carl F. Cori and his wife Gerty T. Cori.

There are 3 important routes taken by pyruvate after glycolysis, depending on the organism and the metabolic conditions

  • In aerobic organisms, the pyruvate so formed then enters mitochondria where it is oxidized, with the loss of its carboxyl group as CO2, to form the acetyl group of acetyl-coenzyme A. Later, the acetyl group is completely oxidized to CO2 and H2O by the citric acid cycle with the intervention of molecular oxygen. This pathway is followed by aerobic animal and plant cells.
  • If the supply of oxygen is insufficient, as in vigorously contracting skeletal muscles, the pyruvate cannot be oxidized further for lack of oxygen. Under such conditions, it is then reduced to lactate, a process called anaerobic glycolysis. Lactate is also produced from glucose in anaerobic microorganisms that carry out lactic acid fermentation.
  • In some microorganisms (e.g., brewer’s yeast), the pyruvate formed from glucose is transformed anaerobically into ethanol and CO2, a process called alcoholic fermentation. Since living organisms first arose in an atmosphere devoid of oxygen, anaerobic breakdown of glucose is the most ancient type of biological mechanism for obtaining energy from organic fuel molecules (Lehninger AL, 1984)

Two Phases of Glycolysis

During glycolysis, the 6-carbon glucose is broken down into two moles of 3-carbon pyruvate via 10 enzyme-catalyzed sequential reactions. These reactions are grouped into 2 phases, phase I and II
  1. Phase I or Preparatory Phase It consists of the first 5 steps. In these reactions, glucose is enzymatically phosphorylated by ATP (first at carbon 6 and later at carbon 1) to yield fructose 1,6- diphosphate which is then split in half to yield 2 moles of the 3 carbon compound, glyceraldehyde 3-phosphate. The first phase of glycolysis, thus, results in cleavage of the hexose chain. This phase requires an investment of 2ATP moles to activate (or prime) the glucose mole and prepare it for its cleavage into two 3- carbon pieces. Besides glucose, other hexoses such as D-fructose, D-galactose and D-mannose may also convert into glyceraldehyde 3-phosphate. glycolysis.jpg
  2. Phase II or Payoff Phase The last 5 reactions of glycolysis constitute this phase. This phase represents the payoff of glycolysis, in which the energy liberated during conversion of 3 moles of glyceraldehyde 3-phosphate to 2 moles of pyruvate is converted by the coupled phosphorylation of 4 moles of ADP to ATP. Although 4 moles of ATP are formed in phase II, the net overall yield is only 2 moles of ATP per mole of glucose oxidized, since 2 moles of ATP are invested in phase I. The phase II is, thus, energy conserving.
A noticeable feature of glycolysis is that each of the 9 metabolic intermediates between glucose and pyruvate is a phosphorylated compound. The phosphoryl groups in these compounds are in either ester or anhydride likage. The phosphoryl or phosphate groups perform the following 3 functions :
  1. The phosphate groups are completely ionized at pH 7, so that each of the 9 intermediates of glycolysis gains a net negative charge. Since cell membranes are, in general, impermeable to charged molecules, the glycolytic intermediates cannot escape from the cell. Only glucose can enter cells and pyruvate or lactate can leave cells because cell membranes have specific transport systems that allow these molecules to pass.
  2. The phosphate groups are essential components in the conservation of energy since they are ultimately transferred to ADP to produce ATP.
  3. The phosphate groups act as recognition or binding groups required for the proper fit of the glycolytic intermediates to the active site of their corresponding enzymes.


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