19.1 Glycolysis

Introduction

My main thesis will be that in the study of the intermediate processes of metabolism we have to deal not with complex substances which elude ordinary chemical methods, but with the simple substances undergoing comprehensible reactions.

You have read that nearly all of the energy used by living cells comes to them in the bonds of the simple 6-carbon sugar, glucose. Glycolysis (literally "sugar splitting") is the first step in the breakdown of glucose to extract energy for cellular metabolism. Nearly all living organisms carry out glycolysis as part of their metabolism. The process does not use oxygen and is therefore anaerobic . Glycolysis takes place in the cytoplasm of both prokaryotic and eukaryotic cells.

Glycolysis begins with the six carbon ring-shaped structure of a single glucose molecule and ends with two molecules of a three-carbon sugar called pyruvate . Glycolysis consists of two distinct phases. The first part of the glycolysis pathway traps the glucose molecule in the cell and uses energy to modify it so that the six-carbon sugar molecule can be split evenly into the two three-carbon molecules. The second part of glycolysis extracts energy from the chemical bonds in the molecules and stores it in the form of ATP and NADH, the reduced form of NAD.

First half of glycolysis (energy-requiring steps)

Step 1 . The first step in glycolysis ( [link] ) is catalyzed by hexokinase, an enzyme with broad specificity that catalyzes the phosphorylation (addition of a phosphate molecule) of six-carbon sugars. Hexokinase phosphorylates glucose using ATP as the source of the phosphate, producing glucose-6-phosphate, a more high-energy form of glucose. This reaction prevents the phosphorylated glucose molecule from being transported out of the cell via glucose transporters in the plasma memrane. It can no longer leave the cell because the transport proteins recognize unmodified glucose, but not the phosphorylated version.

Step 2 . In the second step of glycolysis, an isomerase converts glucose-6-phosphate into one of its isomers, fructose-6-phosphate. An isomerase is an enzyme that catalyzes the conversion of a molecule into one of its isomers (compounds with the same numbers and kinds of atoms arranged in different configurations). This change from phosphoglucose to phosphofructose facilitates the eventual split of the sugar into two three-carbon molecules.

Step 3 . The third step is the phosphorylation of fructose-6-phosphate, catalyzed by the enzyme phosphofructokinase. A second ATP molecule donates a high-energy phosphate to fructose-6-phosphate, producing fructose-1,6- bi sphosphate. In this pathway, phosphofructokinase is a rate-limiting enzyme. It is active when the concentration of ADP is high; it is less active when ADP levels are low and the concentration of ATP is high. Thus, if there is “sufficient” ATP in the system, the pathway slows down. This is a type of end product inhibition, since ATP is the end product of glucose catabolism.