Glycolysis

Overview

Glycolysis is a metabolic pathway(a series of linked chemical reactions that occur in the

cell) that breaks down glucose into pyruvate, generating energy. This energy is stored in the form

of ATP(adenosine triphosphate)[3]. Glycolysis yields a total of 2 ATP, two NADH(nicotinamide

adenine dinucleotide) and two pyruvate molecules per glucose[2]. Glycolysis does not require

oxygen to take place[3]. Glycolysis is a series of ten reactions that are each catalyzed

(accelerated/ by enzymes(proteins that speed up biological reactions)[3]. Glycolysis can be

understood as three distinct stages. In the first stage, Glucose is trapped within the cytosol(inside

the cell) of the cell where its structure is destabilized[1]. The second stage is when glucose is

broken down into two three-carbon molecules and finally stage three is when ATP is

produced[1].

Biochemistry. 5th edition.

Before Glycolysis can begin, Glucose has to be able to make its way into the cell. The

way Glucose is transported into the cell is by the help of a membrane protein[2]. Once this

occurs, hexokinase(an enzyme) catalyzes the addition of a phosphoryl group from an ATP

molecule onto carbon number 6 of the glucose[2]. There are two important reasons a phosphoryl

group is added to glucose. The first reason a phosphoryl groups is added to a glucose is to

convert it into Glucose 6-phosphate, changing its chemical nature[1]. Changing the chemical

nature of glucose prevents it from being able to leave the inside of the cell[1]. Membrane

transport proteins are now unable to transport glucose back out of the cell because of this

chemical change[2]. The second reason why a phosphoryl group is added to the glucose is to

destabilize its structure[1]. When the structure of glucose is destabilized, glucose enters a higher

energy state that makes it more reactive and suitable to continue down the glycolytic pathway to

be broken down into smaller compounds[1].

Next, Isomerization takes place to convert glucose 6-phosphate into fructose 6-

phosphate[2]. Glucose 6-phosphate exist in its cyclic confirmation(form)[1]. When glucose

molecules exist in their cyclic form, they do not readily undergo reaction because the aldehyde

group or ketone group is not exposed[2]. Therefore, to be able to continue down the glycolytic

pathway Glucose 6-phosphate must have its ketone or aldehyde group exposed[1].

Phosphoglucose isomerase (an enzyme that changes a molecule to one of its isomers)

[2]accomplishes this by opening glucose 6-phosphate into its open chain confirmation[1].

Phosphoglucose isomerase then catalyzes it into a fructose 6-phosphate in its cyclic-chain

phosphoryl group is added by phosphofructokinase(enzyme), converting fructose 6-phosphate

into fructose 1,6-bisphosphate and committing it to the glycolytic pathway[1].

Stage 2

The aim of stage two is to cleave the fructose 1,6-bisphosphate into two three carbon

molecules called glyceraldehyde 3-phosphate. Aldolase(enzyme) catalyzes the breakdown of

fructose 1,6-bisphosphate into two different 3-carbon molecules; glyceraldehyde(GAP) and

dihydroxyacetonephosphate(DHAP)[2]. The Glyceraldehyde lies directly on the glycolytic

pathway, ready to move on to stage 3. DHAP does not lie directly on the glycolytic pathway and

must be therefore converted into GAP by isomerization [1]. Triose phosphate isomerase

catalyzes the rapid and reversible conversion of DHAP to GAP[1]. Trios phosphate isomerase

catalyzes the conversion of DHPA into GAP via an intramolecular redox reduction in which a

hydrogen is transferred from the carbon 1 on DHAP to its carbon 2[1].

Stage 3

This is the stage where all the ATP molecules are formed. The first part of stage three is

the conversion of glyceraldehyde 3-phosphate into 1,3-bisphosphoglyerate by glyceraldehyde 3-

phosphate dehydrogenase(enzyme)[1].1,3- Bisphosphate is an acyl phosphate and acyl

phosphates have a high phosphoryl-transfer potential. A high phosphoryl-transfer potential is

needed to more easily transfer a phosphoryl group onto an adenosine diphosphate molecule to

convert it into ATP[1]. In this reaction, two processes must be coupled so that the second

reaction can happen at a biologically significant rate[1]. The first process is thermodynamically

favorable and drives the second unfavorable reaction[1]. The first process of this reaction is the
oxidation of the aldehyde to carboxylic acid by NAD+[1]. NAD+ is the oxidized(removing

electrons) form of NADH(nicotinamide adenine dinucleotide hydrogen) and is

reduced(accepting electrons) to NADH once a hydride ion is transferred to it[1]. The second

process is the joining of carboxylic acid and an orthophosphate to form 1,3

-Bisphosphoglycerate[1]. In this second process, NAD+ helps polarize the carboxylic acid that is

attacked by an orthophosphate, facilitating the formation of 1,3 -Bisphosphoglycerate[1].

In the third and final stage of glycolysis is where the generation of ATP from 1,3-

Bisphosphoglycerate occurs in a substrate-level phosphorylation[1]. 1,3- Bisphosphoglycerate is

a substrate with a high phosphoryl-transfer potential. Phosphoglycerate kinase catalyzes the

transfer of the phosphoryl group from the substrate to ADP to form ATP and 3-

phosphoglycerate[1]. Unlike 1,3- bisphosphoglycerate, 3-phosphoglycerate does not have a high

phosphoryl-transfer potential and needs to in order to proceed down the glycolytic pathway[1].

This is made possible by first rearranging 3-phosphoglycerate into a more reactive form 2-

phosphoglycerate[1]. Phosphoglycerate mutase catalyzes this rearrangement, moving the

phosphoryl group from the third carbon on the 3-phosphoglycerate to its second carbon[1]. Once

the 2-phosphoglycerate molecule is formed, the next step is to transform 2-phosphoglycerate into

a molecule that has a higher phosphoryl transfer potential, since 2-phosphoglycerate has a low

phosphoryl transfer-potential and would be unable to continue down the glycolytic pathway[1].

It must be noted that this reaction requires catalytic amounts of 2,3-bisphosphoglycerate

proceed[1]. Phosphoenolpyruvate is an enol that has a higher transfer-potential than 2-

phosphoglycerate and is able to continue down the glycolytic pathway[1]. Phosphoenolpyruvate

is formed by the dehydration of 2-phosphoglycerate[1]. The enzyme that catalyzes this reaction

is enolase. Finally, the transfer of a phosphoryl group from phosphoenolpyruvate to ADP is

ends upyielding a net total of two ATP molecules, two pyruvates, and two NADH molecules[2].

Biochemistry. 5th edition.

Tumor cells change their metabolism in favor of glycolysis[4]. Normally, a cell depends

on mitochondrial oxidative metabolism for energy production which is much more efficient than

the glycolytic pathway[4]. When this occurs under oxygen-sufficient conditions it is known as

the Warburg effect[4]. Three reasons have been identified as to why tumors cells switch their

metabolism from oxidative metabolism in the mitochondria to glycolysis[4]. The first reason is

to ease the generation of precursors that are required for the rapid proliferation of tumor cells[4].

The second reason is because glycolysis is and faster and finally because this switch protects the

tumor cells from oxidative stress that might otherwise occur from radicals created during

oxidative metabolism[4]. This over-reliance of cancer cells on glycolysis results in the drug

resistance of certain classes of anti-tumor drugs[4]. The relationship between cancer cells and

glycolysis is a marked characteristic of cancer and one that researchers have looked at to create a

treatment for cancer[5].

1. Berg JM, Tymoczko JL, Stryer L. Biochemistry. 5th edition. New York: W H Freeman;

2002. Section 16.1, Glycolysis Is an Energy-Conversion Pathway in Many

Organisms. Available from: https://www.ncbi.nlm.nih.gov/books/NBK22593/

2. Boundless, “Boundless Biology,” Lumen. [Online]. Available:

https://courses.lumenlearning.com/boundless-biology/chapter/glycolysis/. [Accessed: 01-

Mar-2021].

3. “Glycolysis,” Wikipedia, 20-Feb-2021. [Online]. Available:

https://en.wikipedia.org/wiki/Glycolysis#Overview. [Accessed: 01-Mar-2021].

4. Fabrizio Marcucci, Cristiano Rumio, Glycolysis-induced drug resistance in tumors—A

response to danger signals?, neoplasia, Volume 23, Issue 2, 2021,Pages 234-245, ISSN

1476-5586, https://doi.org/10.1016/j.neo.2020.12.009.

(https://www.sciencedirect.com/science/article/pii/S1476558620301901)

5. Kheshwant S. Gill, Philana Fernandes, Tracey R. O'Donovan, Sharon L. McKenna,

Kishore K. Doddakula, Derek G. Power, Declan M. Soden, Patrick F. Forde, Glycolysis

inhibition as a cancer treatment and its role in an anti-tumour immune response,

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer,Volume 1866, Issue

1,2016,Pages 87-105,ISSN 0304-419X,https://doi.org/10.1016/j.bbcan.2016.06.005.

(https://www.sciencedirect.com/science/article/pii/S0304419X16300452)
Post-write

I used partitioning, principle of operation, and graphics as definition strategies in

my extended definition. I used partitioning to divide the process of glycolysis into three

distinct stages. I used the principle of operation to describe the way glycolysis works

throughout my extended definition. I used a graphic right after the overview paragraph on

the first page and another graphic after the stage three paragraphs on page five.