Glycolysis Enzymes: Difference between revisions

The first step of the pathway is the conversion of <scene name='39/392339/Cv/3'>glucose</scene> to <scene name='39/392339/Cv/4'>glucose-6-phosphate</scene> by either hexokinase or glucokinase. Hexokinases should not be confused with glucokinase, which is a specific isoform of hexokinase. All hexokinases are capable of phosphorylating several hexoses but glucokinase acts with a 50-fold lower substrate affinity and its main hexose substrate is glucose.[https://en.wikipedia.org/wiki/Hexokinase]

<scene name='39/392339/Cv/4'>Glucose-6-phosphate</scene> isomerizes to <scene name='39/392339/Cv1/1'>fructose-6-phosphate</scene>; this reaction is catalyzed by [[Stancu_Phosphoglucoisomerase_Sandbox_1|phosphoglucoisomerase]]. This isomerization allows for the creation of two, three carbon sugars as a product.

[[Austin_Drake_Sandbox|Aldolase]] catalyzes the retro-aldol cleavage of <scene name='39/392339/Cv/8'>fructose 1,6-bisphosphate</scene> into two three-carbon phosphosugars, <scene name='39/392339/Cv/9'>dihydroxyacetone phosphate</scene> and <scene name='39/392339/Cv/10'>glyceraldehyde-3-phosphate</scene>.

The reaction is an aldol cleavage, or otherwise termed, retro aldo condensation.  Catalysis occurs first when the nucleophilic ε-amine group of Lys229 attacks the carbonyl carbon of the substrate (FBP) in its open-ring state, pushing an electron pair to the oxygen of the carbonyl. The oxygen is protonated and leaves as water as a protonated <scene name='Austin_Drake_Sandbox/Schiff_base/2'>Schiff base</scene> is produced (an imine resulting from a ketone and amine) with the open-ring form of FBP  

First, [[Nathan_Line_sandbox_3|glyceraldehyde-3-phosphate dehydrogenase]] oxidizes <scene name='39/392339/Cv/11'>glyceraldehyde-3-phosphate</scene>, transferring a hydride to NAD+, generating NADH and H+. A phosphate ion is used instead of a water molecule, leading to the formation of <scene name='39/392339/Cv/12'>1,3-bisphosphoglycerate</scene>, a high energy compound.

[[Phosphoglycerate Kinase]] catalyzes the transfer of a phosphate from the 1 position of <scene name='39/392339/Cv/12'>1,3-bisphosphoglycerate</scene> to ADP. This is the "break even" point of glycolysis: the two ATPs that were consumed in preparing for the cleavage have been now been regenerated, in addition to two molecules of NADH, which can be used to generate ATP through electron transport and oxidative phosphorylation. Phosphoglycerate kinase is the seventh enzyme in the cycle which catalyzes the reaction of 1,3-Biphosphoglycerate and ADP to produce <scene name='39/392339/Cv/13'>3-Phosphoglycerate</scene> and <scene name='Shane_Harmon_Sandbox/Atp/4'>ATP</scene>. This method for ATP production is known as substrate-level phosphorylation because it produces energy storing ATP molecules without the use of oxygen, NADH, or an ATPase. The reaction is highly exergonic allowing it to be coupled with the less thermodynamically favored GADPH reaction of the cycle so both reactions occur spontaneously.

The resultant <scene name='39/392339/Cv/13'>3-phosphoglycerate</scene> isomerizes to <scene name='39/392339/Cv/14'>2-phosphoglycerate</scene> in a reaction catalyzed by [[Phosphoglycerate Mutase|phosphoglycerate mutase]].  

A second high energy intermediate, <scene name='39/392339/Cv/15'>phosphoenolpyruvate</scene>, is formed by [[Enolase]].  

The final reaction of the pathway is catalyzed by [[Pyruvate Kinase|pyruvate kinase]], which converts phosphoenolpyruvate to <scene name='39/392339/Cv/16'>pyruvate</scene>, while generating ATP from ADP.

Under oxidative conditions, pyruvate continues to be metabolized through the [[The_Citric_Acid_Cycle|tricarboxylic acid cycle]].  While energy can be obtained under anaerobic conditions from glycolysis alone, the accumulation of pyruvate and NADH limits this. There are two main strategies for dealing with this problem. In most cells, [[Lactate_Dehydrogenase|lactate dehydrogenase]] converts the pyruvate and NADH to lactate, dealing with both problems at once and regenerating NAD+ so glycolysis can continue. Fortunately for us, some yeast cells do something else--leading to the generation of ethanol. First, [[Pyruvate decarboxylase|pyruvate decarboxylase]] catalyzes the converstion from pyruvate to acetaldehyde, releasing carbon dioxide. Next, aldehyde dehydogenase reduces the acetaldehyde to ethanol, converting NADH to NAD+ in the process.