Biochemistry/Glycolysis

Introduction

In fact, glycolysis considered a linear pathway of ten enzyme-mediated steps. The pathway for glycolysis has two phases: the energy investment phase and energy generation phase. The first five steps in the glycolysis are the energy investment "preparatory phase", which produce glyceraldehyde and three phosphate. Energy generation phase "payoff phase" is the last five steps of glycolysis, which produce the final two pyruvate molecules product. Glycolysis can occur in the presence or absence of oxygen, which called aerobic and anaerobic glycolysis respectively. In the body, the source of glucose for glycolysis come from dietary disaccharides and monosaccharides. Glycolysis is the process by which glucose is converted to two molecules of pyruvate. It is the first step in carbohydrate metabolism, the end result of which is the conversion of glucose to carbon dioxide and water. In this process, a large amount of energy is converted into ATP.

During glycolysis, two molecules of NADH and a net two molecules of ATP are generated (two molecules of ATP are used to get the pathway started, but four molecules are then synthesized). Thus, there is a net production of two ATP molecules for each glucose molecule converted to two molecules of pyruvate.

The Ten Steps of Glycolysis

This is not correct, enzyme two is phosphohexose isomerase

Visual Overview of Reactions

Stage I: Energy Investment Stage II: Energy Harvesting

Detailed Description of Reactions

(1) Glucose that enters the cell has only one fate: it is converted to glucose-6-phosphate by a typical kinase reaction. A pyrophosphate bond is cleaved (-7.5 kcal/mole) and a phosphate ester bond is formed (+3 kcal/mole), resulting in a net -4.0 kcal/mole. Therefore, this reaction is irreversible.

(2) Glucose-6-phosphate is then converted into Fructose-6-phosphate by a reversible isomerization.

Note: at body pH, phosphate groups are ionized, so PO3H2 would really be PO3(2-).

Glycolysis Enzymes: 1. Hexokinase 2. Phosphoglucoisomerase 3. Phosphofructokinase 4. Aldolase 5. Triose phosphate isomerase 6. Glyceraldehyde-3-phosphate dehydrogenase 7. Phosphoglycerate kinase 8. Phosphoglycerate mutase 9. Enolase 10. Pyruvate kinase Compounds: ATP ADP Glucose Pyruvate

Glycolysis, an overview

Glycolysis is a central pathway for the catabolism of carbohydrates in which the six-carbon sugars are split to three-carbon compounds with subsequent release of energy used to transform ADP to ATP. Glycolysis can proceed under anaerobic (without oxygen) and aerobic conditions. Glycolysis, an overall equation

Glycolysis is a 10-step pathway which converts glucose to 2 pyruvate molecules. The overall Glycolysis step can be written as a net equation: Glucose + 2xADP + 2xNAD+ -> 2xPyruvate + 2xATP + 2xNADH

Glycolysis consists from two main phases. First phase, energy investment. During this step 2xATP are converted to 2xADP molecules. Second phase, energy generation. During this step 4xADP are converted to 2xATP molecules and 2xNAD+ are converted to 2xNADH molecules. Glycolysis: Energy investment phase

Glycolysis step 1: Glucose phosphorylation catalysed by Hexokinase: α-D-Glucose + ATP -> α-D-Glucose-6-phosphate + ADP + H+ δGo = -16.7 kJ/mol

Glycolysis step 2: Isomerization of glucose-6-phosphate catalysed by Phosphoglucoisomerase: α-D-Glucose-6-phosphate <=> D-Fructose-6-phosphate δGo = +1.7 kJ/mol

Glycolysis step 3: Second phosphorylation catalysed by Phosphofructokinase: D-Fructose-6-phosphate + ATP -> D-Fructose-1,6-bisphosphate + ADP + H+ δGo = -18.5 kJ/mol

Glycolysis step 4: Cleavage to two Triose phosphates catalysed by Aldolase: D-Fructose-1,6-bisphosphate <=> Dihydroxyacetone phosphate + D-glyceroaldehyde-3-phosphate δGo = +28 kJ/mol

Glycolysis step 5: Isomerization of dihydroxyacetone phosphate catalysed by Triose phosphate isomerase: Dihydroxyacetone phosphate <=> D-glyceroaldehyde-3-phosphate δGo = +7.6 kJ/mol

3-Bisphosphoglycerate Glycolysis step 6: Generation of 1,3-Bisphosphoglycerate catalysed by Glyceraldehyde-3-phosphate dehydrogenase: D-glyceroaldehyde-3-phosphate + NAD+ +Pi <=> 1,3-Bisphosphoglycerate + NADH + H+ δGo = +6.3 kJ/mol

3-Phosphoglycerate Glycolysis step 7: Substrate-level phosphorylation, 3-Phosphoglycerate catalysed by Phosphoglycerate kinase: 1,3-Bisphosphoglycerate + ADP <=> 3-Phosphoglycerate + ATP δGo = -18.8 kJ/mol

Glycolysis step 8: Phosphate transfer to 2-Phosphoglycerate catalysed by Phosphoglycerate mutase: 3-Phosphoglycerate <=> 2-Phosphoglycerate δGo = +4.4 kJ/mol

Glycolysis step 9: Synthesis of Phosphoenolpyruvate catalysed by Enolase: 2-Phosphoglycerate <=> Phosphoenolpyruvate + H2O δGo = +1.7 kJ/mol

Glycolysis step 10: Substrate-level phosphorylation. Pyruvate synthesis catalysed by Pyruvate kinase: Phosphoenolpyruvate + H+ + ADP -> Pyruvate + ATP δGo = -31.4 kJ/mol Anaerobic and Aerobic Glycolysis

Glycolysis is an ancient metabolic pathway which was probably developed about 3.5 billion years ago when there is no oxygen was available. That is why main Glycolysis Glycolysis step s are not require oxygen. Products from Glycolysis then can follow anaerobic and aerobic pathways. Anaerobic Glycolysis pathway

For anaerobic Glycolysis pathway there are two major fermentation processes exists.

Lactic acid fermentation. This pathway is common for animal cells and lactic acid bacteria. In animals the anaerobic glycolysis take place in many tissues. Red blood cells take most of the energy from anaerobic metabolism. Skeletal muscle take energy from glycolysis and from respiration. The lactate produced utilise through diffusion from the tissues to bloodstream and then to aerobic tissues, such as liver and heart. In these aerobic tissues lactate can be catabolized further or can be converted back through gluconeogenesis.

One step conversion of Pyruvate to Lactate catalysed by Lactate dehydrogenase. δGo = -25.1 kJ/mol Alcoholic fermentation. This two-step pathway is common for yeast.

Pyruvate -> Acetaldehyde + CO2 catalysed by Pyruvate decarboxylase. This reaction requires thiamine pyrophosphate, derived from vitamin B1 as a coenzyme.

Conversion of Acetaldehyde to Ethanol by Alcohol dehydrogenase. Aerobic Glycolysis pathway

With the present of oxygen in cells pyruvate is oxidized to acetyl-CoA, which then enters the citric acid cycle. The NADH molecules are reoxidized through the with electrons transferred to the O2 molecules. The aerobic Glycolysis consists from two major steps:

Glucose + 2xADP + 2xPi + 2xNAD+ => 2xPyruvate + 2xATP + 2xNADH + 2H+ + 2xH2O

NADH oxidation pathway which generaly take place in the mitochohdrion: 2xNADH + 8xH+ + O2 + 6xADP + 6xPi => 2xNAD+ + 8H2O + 6xATP

The final net equation for aerobic Glycolysis:

Glucose + 8xADP + 8xPi + 8xH+ + O2 => 2xPyruvate + 8xATP + 10xH2O Aerobic and anaerobic glycolysis. Overview

The metabolism of glucose trough aerobics or anaerobic pathways is a nonoxidative process. Both types of glycolysis release a small fraction of potential energy stored in the glucose molecules. During the first 10 steps of glycolysis, only a small part of all glucose energy is released and the rest of the potential energy is released during the last steps after glycolysis. For this reason aerobic degradation is much more efficient than anaerobic metabolism. That is why the aerobic mechanism is now much more spread within living organisms, but nevertheless anaerobic pathways still take place even in animals under certain physiological circumstances.