Unraveling the Mysteries of Carbohydrate Metabolism for Glucose or Glycogen Break-Down

"Glycolysis is a fundamental process in biochemistry that plays a critical role in the production of energy within cells. As a healthcare professional, understanding the intricacies of glycolysis is essential to delivering effective care to patients. In this comprehensive guide, we'll explore the various types of glycolysis, the steps involved, and how to calculate ATP production in both aerobic and anaerobic conditions. We'll also delve into the fate of pyruvate and the diseases that can result from abnormalities in glycolysis. Whether you're a medical student, nurse, paramedic, or biochemist, this article will provide valuable information for your exams and professional growth."

Glycolysis and ATP Calculations for Healthcare Professionals
From Biochemistry Library of H.E.S (Health, Education, and Skills)

Glycolysis | Embden Meyerhoff Pathway

The 10 steps process of breakdown of Glucose or Glycogen up to Pyruvate or Lactate is termed Glycolysis.

Glycolysis is a catabolic process.
It is the main pathway of Carbohydrate metabolism to generate energy i.e. ATPs.
It occurs in the cytosol of the cell.
It produces ATP, NADH2, and Pyruvate (the end products of Glycolysis).
Glycolysis act as a metabolic spark plug, generating energy to fuel the cell's activities, like a factory producing goods.
In simple terms, glycolysis converts sugar into energy to keep the cells and body functioning optimally.

Significance of Glycolysis

A crucial source of energy: By breaking down glucose, glycolysis provides energy for cells (especially Brain cells) to perform various functions, because among Carbohydrates brain utilizes only Glucose as a primary source of energy.
Helps in maintaining blood sugar levels: Glycolysis helps regulate blood sugar levels and prevents them from becoming too high or too low.
Provides precursors for other metabolic pathways: The end products of glycolysis serve as precursors (in the form of Pyruvate) for other metabolic pathways, such as the citric acid cycle and fatty acid synthesis. Thus Glycolysis is the main pathway for the metabolism of other Hexoses (Fructose, and Galactose).
Involved in diseases: Abnormalities in glycolysis have been linked to several diseases, including Hemolytic Anemia, cancer, and diabetes. Understanding glycolysis and its regulation may lead to the development of new therapeutic strategies for these diseases.
Glycolysis remains conserved over time: The process of glycolysis has been conserved throughout evolution, indicating its fundamental importance for cellular metabolism all the time.

Types of Glycolysis

There are two types of glycolysis: aerobic glycolysis and anaerobic glycolysis.
Both types of glycolysis are regulated by different enzymes, which control the rate at which glucose is broken down. This regulation ensures that cells have the energy they need to function properly, no matter the conditions they face.

a. Aerobic glycolysis

It takes place in the presence of oxygen and is a more efficient way of producing energy.
The end product of Aerobic glycolysis is Pyruvate.
NADH2 is produced which gives 3ATPs through the respiratory chain, which works only in the presence of Oxygen.
A total of 10 ATPs are formed, 2 ATPs are utilized and the net gain is 8 ATPs.

b. Anaerobic glycolysis

It occurs in the absence of oxygen.
The end product of anaerobic glycolysis is Lactate.
The respiratory chain stops in the absence of Oxygen (O2). Therefore the NADH2 produced in Anaerobic Glycolysis cannot give 3 ATPs instead it reduces Pyruvate to Lactate.
This type of glycolysis is less efficient and produces a smaller amount of ATP compared to aerobic glycolysis i.e. total of 4 ATPs are formed, 2 ATPs are utilized and the net gain is 2 ATPs. However, it is still a crucial process for cells as it provides energy for cell survival when oxygen is not available.
Another type of glycolysis that has been studied is Fermentative glycolysis, which occurs in microorganisms such as yeast and bacteria. Fermentative glycolysis is a type of anaerobic glycolysis that generates ATP and other end products like ethanol or lactic acid. This type of glycolysis is used by microorganisms to generate energy in the absence of oxygen and is a crucial process in the food and beverage industry, as it is used to produce fermented products like bread, beer, and yogurt.

Comparison Between Aerobic and Anaerobic Glycolysis

Basis of distinction	Aerobic Glycolysis	Anaerobic Glycolysis
*Presence or Absence of Oxygen*	Aerobic glycolysis occurs in the presence of oxygen and is a more efficient process,	Anaerobic glycolysis occurs in the absence of oxygen and is less efficient.
*Mechanism of ATP generation*	Aerobic glycolysis takes place in the cytoplasm of cells and is the first stage of cellular respiration. In this process, glucose is broken down into two molecules of pyruvate, producing a small amount of ATP (adenosine triphosphate) and producing energy for the body. The pyruvate produced in aerobic glycolysis is then transported into the mitochondria, where it undergoes further metabolism in the citric acid cycle and the electron transport chain. These two stages of cellular respiration are the most efficient way of producing energy for the body, and together with aerobic glycolysis, they produce a large amount of ATP.	Anaerobic glycolysis occurs in the absence of oxygen. This process takes place in the cytoplasm of cells and is the first stage of anaerobic respiration. In anaerobic glycolysis, glucose is partially broken down into lactic acid, producing a small amount of ATP. Unlike aerobic glycolysis, the lactic acid produced in anaerobic glycolysis cannot be transported into the mitochondria and is instead used as a source of energy by the body.
*Number of Energy Generation*	Aerobic glycolysis, as part of the overall cellular respiration process, produces a large amount of ATP, providing cells with more energy to perform various functions. Note: Aerobic glycolysis has a number of advantages over anaerobic glycolysis. It produces a larger amount of ATP, providing cells with more energy to perform various functions.	Anaerobic glycolysis produces a smaller amount of ATP, providing cells with a quick burst of energy, but not enough to sustain their functions for long periods of time.
*Production of by-products and their utilization*	Aerobic glycolysis produces carbon dioxide and water, which are benign byproducts that can be easily disposed of by the body.	Anaerobic glycolysis produces Lactic acid, which can accumulate in the muscles and cause fatigue and pain.

10 Steps of Glycolysis

Here is a step-by-step explanation of the ten steps of glycolysis, including the enzymes involved in each step:

1. Conversion of Glucose to Glucose-6-Phosphate i.e. Glucose Phosphorylation

The first step in glycolysis is the phosphorylation of glucose, which activates the molecule and makes it easier to break down.
This reaction is catalyzed by the enzyme hexokinase or glucokinase.
1 ATP is utilized to provide Phosphate to glucose. The end result is glucose-6-phosphate.
This reaction controls the rate of Glucose breakdown.
This reaction is irreversible, meaning that glucose cannot be converted back into its original form once it has been phosphorylated. But can be reversed by Glucose-6-Phosphate Phosphatase (an enzyme of gluconeogenesis).

Role of the Irreversible nature of Glucose Phosphorylation | Extra Note

The irreversible nature of this reaction makes it an excellent point of control for the overall process of glycolysis. When there is a sufficient amount of glucose-6-phosphate available, the enzymes involved in the subsequent steps of glycolysis are activated and the rate of glucose breakdown increases. Conversely, when glucose-6-phosphate is in short supply, the enzymes involved in the subsequent steps of glycolysis are inhibited, which slows down the rate of glucose breakdown.
In addition to its role in controlling the rate of glucose breakdown, glucose phosphorylation also helps to prevent the leakage of glucose from the cell. This is because once glucose has been phosphorylated and converted into glucose-6-phosphate, it cannot cross the cell membrane without the help of a specific transporter. This means that the cell can regulate the availability of glucose by controlling the rate of glucose phosphorylation and the amount of glucose-6-phosphate that is available for breakdown.

2. Isomerization of Glucose-6-Phosphate to Fructose-6-Phosphate

Glucose-6-phosphate is converted into fructose-6-phosphate through a process called isomerization, which is catalyzed by the enzyme Phosphohexose Isomerase (also known as Glucohexokinase).
The isomerization of glucose-6-phosphate to fructose-6-phosphate is a simple structural change, in which the position of a single bond is shifted.
This reaction is energetically favorable, meaning that it occurs spontaneously and does not require an input of energy.
Fructose-6-phosphate is a substrate for the next enzyme in the pathway, which is aldolase. In the absence of fructose-6-phosphate, the aldolase reaction cannot proceed, and the rate of glycolysis is slowed down.

3. Phosphorylation of Fructose-6-Phosphate

Fructose-6-phosphate is then phosphorylated again, this time by the enzyme Phosphofructokinase.
The end product of this reaction is Fructose-1,6-bisphosphate.
Again 1 ATP is utilized to provide Phosphate in this reaction. (Total of 2 ATPs are utilized up to this step)
It is also an irreversible reaction for the same enzyme.
However, the reaction can be reversed by Fructose 1,6-bisphosphatase (an enzyme of Glyconeogenesis).
It is a rate-limiting reaction.

The term "rate-limiting reaction" refers to the step in a metabolic pathway that determines the overall speed of the reaction. In other words, it is the step that controls how quickly the entire reaction takes place.

In the case of the phosphorylation of fructose-6-phosphate, it means that this step the step that limits the speed of the glycolysis pathway as a whole. If this step proceeds slowly, the entire reaction of glycolysis will proceed slowly. On the other hand, if this step proceeds quickly, the entire reaction of glycolysis will proceed quickly as well.

4. Cleavage of Fructose 1,6-Bisphosphate into two trioses

The next step is the cleavage (splitting) of Fructose 1,6-bisphosphate (a hexose) into two trioses i.e. 3-Phosphoglyceraldehyde, and Dihydroxy-acetone-phosphate (DHAP) by Aldolase.
After Fructose 1,6-Bisphosphate splits into above mentioned two trioses by the action of Aldolase, the pathway will run twice because DHAP is also converted to 3-Phosphoglyceraldehyde.
Each of these two, above-mentioned, trioses produces 1 NADH2 which, in aerobic glycolysis, gives 3 ATPs through the respiratory chain. Therefore two trioses will produce 2 NADH2 which will give 6 ATPs.
While in anaerobic glycolysis, the respiratory chain shuts down, and therefore NADH2 will not be able to produce ATPs at all, instead will be used to reduce Pyruvate to Lactate.
Each of these two trioses produces 2 ATPs at the substrate level, therefore two trioses will produce 4 ATPs at the substrate level.
Each of the two above-mentioned trioses produces 1 Pyruvate. Therefore two trioses will produce 2 Pyruvates or we can say that one glucose molecule produces 2 Pyruvate molecules.

5. Oxidation of 3-Phosphoglyceraldehyde

3-Phosphoglyceraldehyde is oxidized by a dehydrogenase to form 1,3-bisphosphoglycerate.
The 2nd Phosphate is supplied by H3PO4 (Phosphoric Acid) instead of ATP.
H2 (Hydrogen molecule) is released, which reduces NAD to NADH2.
In aerobic conditions, NADH2 provides 3 ATPs through the respiratory chain.
This is the only oxidative step in glycolysis.

6. Phosphorylation of 1,3-bisphosphoglycerate:

1,3-bisphosphoglycerate is phosphorylated by phosphoglycerate kinase to form 3-phosphoglycerate.
1 Phosphate is released, which is taken up by the ADP and becomes ATP i.e. 1 ATP is produced at the substrate level.

7. Oxidation of 3 Phosphoglycerate

3-phosphoglycerate is oxidized by phosphoglycerate mutase to form 2-phosphoglycerate.
In this step the molecule (3 Phosphoglycerate) undergoes a rearrangement of its functional groups, leading to the formation of 2-phosphoglycerate.
During this process, a hydrogen atom is transferred from the 3-carbon to the 2-carbon, resulting in the oxidation of the 3-carbon and the reduction of the 2-carbon.

8. Phosphorylation of 2-Phosphoglycerate

2-phosphoglycerate is phosphorylated by enolase to form phosphoenolpyruvate (PEP).
In the phosphorylation of 2-phosphoglycerate, the molecule is converted to phosphoenolpyruvate (PEP) by the transfer of a phosphate group from ATP to the hydroxyl group on the 2-carbon.
This reaction results in the formation of a high-energy phosphate bond in PEP, which can be utilized by the cell to produce ATP.

9. Carboxylation of Phosphoenolpyruvate

Phosphoenolpyruvate (PEP) is converted into enol pyruvate (before yielding pyruvate).
This reaction is catalyzed by the enzyme pyruvate kinase and results in the transfer of a phosphate group from PEP to ADP, forming ATP and enol pyruvate.

10. Conversion of PEP to Pyruvate

The tenth and final step of glycolysis involves the conversion of phosphoenolpyruvate (PEP) into pyruvate, (which is a key intermediate in cellular metabolism and can be further metabolized to form other compounds such as lactate, acetyl-CoA, and alanine, among others).
This reaction is catalyzed by the enzyme pyruvate kinase and is accompanied by the transfer of a phosphate group from PEP to ADP, forming ATP.

PEP + ADP -> Pyruvate + ATP

Pyruvate kinase catalyzes this reaction by binding PEP and ADP and facilitating the transfer of the phosphate group from PEP to ADP. The resulting ATP molecule can be used by the cell for energy, while pyruvate can be further metabolized in other pathways such as Lactate fermentation or the citric acid cycle. This step represents the end of glycolysis and the release of energy from glucose.
The reaction is regulated by various factors such as the availability of ATP, the concentration of glucose, and the need for energy by the cell, among others.

Conversion from Pyruvate to Lactate (Lactate Fermentation)

The significance of this reaction is that in the anaerobic conditions, the respiratory chain stops therefore the NADH2 produced, during the breakdown of 3-Phosphoglyceraldehyde cannot enter the respiratory chain and is, therefore, unable to produce 3 ATPs. Instead, this NADH2 reduces Pyruvate to Lactate and itself becomes NAD.
This NAD is re-utilized in the reaction of 3-Phosphoglyceraldehyde dehydrogenase. Thus it keeps the pathway running for some time in anaerobic conditions.
When anaerobic conditions abate, the respiratory chain becomes active, and Lactate is converted back to Pyruvate and the same NAD takes back the H2 and becomes NADH2 and then gives 3 ATPs through the respiratory chain (Oxidative Phosphorylation).

Fate of Pyruvate

Pyruvate (a ketoacid) is the end product of aerobic glycolysis and it provides many important substrates for different metabolic processes. These are discussed below

I. Pyruvate enters Citric Acid Cycle

Pyruvate is the end product of glycolysis and is a critical molecule in cellular metabolism.
It can enter the Citric Acid Cycle (also known as the Kreb cycle or the Tricarboxylic Acid Cycle) in two different ways.
(a) Pyruvate can be converted into acetyl-CoA, which then enters the citric acid cycle.
Catalyzed by the enzyme Pyruvate dehydrogenase complex.
The dehydrogenase complex is a complex of three enzymes i.e. Pyruvate Decarboxylase, dihydrolipoyl Transacetylase, and dihydrolipoyl dehydrogenase.
The reaction requires five co-enzymes i.e. NAD, FAD, TPP, CoA, and Lipoic acid.
This reaction provides NADH2, which gives 3 ATPs through Oxidative Phosphorylation.
This is an irreversible reaction. There is no enzyme in the body that can convert Acetyl Co-A back to Pyruvate.
(b) Pyruvate can be converted into oxaloacetate, which then enters the citric acid cycle. Both processes occur in the mitochondria, which is the cell's power center, where energy is produced through oxidative metabolism.

II. Pyruvate enters Gluconeogenesis

Pyruvate, the end product of glycolysis, can also enter the process of gluconeogenesis, which is the biosynthesis of glucose from non-carbohydrate precursors.
This process occurs in the liver and kidneys and serves to maintain blood glucose levels during periods of low carbohydrate intake or high energy demand.
Pyruvate provides phosphoenol pyruvate, the main substrate of gluconeogenesis.
Pyruvate to Phosphoenol Pyruvate is a two-step reaction i.e. first pyruvate will convert to oxaloacetate, and then oxaloacetate will convert to phosphoenol pyruvate.
Pyruvate to Oxaloacetate is catalyzed by Pyruvate Carboxylase and Biotin (coenzyme).
Oxaloacetate to Phosphoenol Pyruvate is catalyzed by Phosphoenol Pyruvate Carboxykinase.
Phosphoenol Pyruvate then starts gluconeogenesis and synthesizes glucose.
It is important to remember that to form glucose from Pyruvate through gluconeogenesis, the body needs two enzymes i.e. Pyruvate Carboxylase with Biotin and Phosphoenol pyruvate carboxykinase.
The two reactions are irreversible for the same enzyme.

III. Pyruvate forms Malic Acid

The conversion of Pyruvate to Malic acid (Malate) is a crucial step in the metabolism of Humans, certain plants, and microorganisms.
In Humans, Pyruvate can be converted to Malic acid through Oxaloacetate in the mitochondria.
Again this is a two-step reaction i.e. Pyruvate will first convert to Oxaloacetate, catalyzed by Pyruvate Carboxylase, and requires Carbon-di-Oxide. Then the Oxaloacetate will be converted to Malic acid, catalyzed by Malate dehydrogenase.
The reaction requires NADH2.
Malic acid may enter the TCA cycle or form Malate Shuttle in the mitochondria.
In plants, malic acid is formed as a result of the conversion of pyruvate during photosynthesis, and it serves as an intermediate in the pathway leading to the formation of glucose.
In microorganisms, the formation of malic acid from pyruvate provides a source of energy and helps to maintain the balance of metabolic intermediates.

IV. Pyruvate forms Lactic Acid in Anaerobic Glycolysis

In the absence of Oxygen, Pyruvate is converted to Lactic Acid.
This reaction is catalyzed by Pyruvate dehydrogenase.
This reaction occurs in the cytosol and is reversible.
The reaction is important in RBCs and WBCs, which don't have mitochondria, hence they depend entirely on anaerobic glycolysis for energy.
The reaction is also important in exercising muscles, which become hypoxic during strenuous exercise resulting in increased production of Lactic acid.

V. Pyruvate can synthesize Amino acid

Pyruvate can be converted to Alanine.
It is an irreversible reaction.
Catalyzed by ALT (SGPT) with coenzyme Pyridoxal Phosphate.

VI. Pyruvate in Bacteria forms Alcohol

In bacteria, pyruvate can be converted to produce Alcohol.
Pyruvate to Alcohol is also a two-step reaction.
First pyruvate is converted to acetaldehyde with the release of Carbon-di-Oxide and the acetaldehyde is reduced to Ethanol (alcohol).

Glycolysis in RBCs

RBCs do not have mitochondria and hence therefore no respiratory chain occurs. Therefore due to this absence of mitochondria in RBCs, the end product of Glycolysis will always be Lactate. In RBCs, there is an alternate pathway of Glycolysis resulting in the formation of 2,3-BPG (2,3-Bisphosphoglycerate).

The process can be broken down into the following steps

1,3 BPG is converted to 2,3-BPG, which is then converted to 3-Phosphoglyceric Acid.
In cells, other than RBCs, 1,3-BPG is converted directly to 3-Phosphoglyceric Acid and produces 1 ATP at the substrate level.
In RBCs, due to the alternate pathway, this 1 ATP at the substrate level will not be formed.

Significance of 2,3-BPG

The molecule 2,3-bisphosphoglycerate (2,3-BPG) plays a crucial role in the transport of oxygen in red blood cells (RBCs).
Its concentration in RBCs is roughly equal to that of hemoglobin (Hb), and it acts as an important regulator of Hb's binding to oxygen (O2).
The presence or absence of 2,3-BPG greatly affects the affinity of Hb for oxygen. This helps to ensure that Hb releases O2 efficiently to the tissues that need it while retaining O2 in the lungs where the partial pressure of O2 is high.
When 2,3-BPG binds to deoxyhemoglobin (Deoxy-Hb), it reduces the Hb's affinity for oxygen, enabling Hb to release O2 more efficiently in tissues, where the partial pressure of oxygen is lower. Conversely, when 2,3-BPG is released from Deoxy-Hb upon oxygenation, Hb's affinity for O2 increases.

In summary, 2,3-BPG plays a critical role in regulating the binding of O2 to Hb in RBCs, and its presence or absence alters the affinity of Hb for oxygen.

ATP Calculation in aerobic and anaerobic glycolysis

The net gain of ATPs in aerobic glycolysis is higher than in anaerobic glycolysis. The reason is that in anaerobic conditions, the respiratory chain shuts down and does not accept protons, electrons, or hydrogen from donors e.g. NADH2. And therefore no ATP will be produced through the respiratory chain in anaerobic conditions. In aerobic conditions, the respiratory chain becomes fully functional and starts producing ATPs.

I. ATP Calculation in Aerobic Glycolysis

2 NADH2 are produced (1 NADH2 by each triose) 1 NADH2 produces 3 ATPs therefore 2 NADH2 will produce 6 ATPs.
4 ATPs are produced at the substrate level (2 ATPs by each triose) by Phosphoglycerate Kinase and Pyruvate Kinase.
2 ATPs are utilized (1 ATP is utilized by Hexokinase/Glucokinase and 1 ATP is utilized by Phosphoftructokinase).
The net calculation will be 6 ATPs (by NADH2) + 4 ATPs (at the substrate level) = 10 ATPs - 2 ATPs (utilized in the 1st and 3rd reactions) = 8 ATPs
If glycolysis starts from Glycogen, 1 ATP utilized by Hexokinase/Glucokinase is spared hence 1 ATP is utilized. In this case, the Net ATP gain will be = 9 ATPs.

II. ATP Calculation in Anaerobic Glycolysis

2 NADH2 are produced (1 NADH2 by each triose). Since the respiratory chain shut down in anaerobic glycolysis, these NADH2 instead of producing ATPs, donate H2 to Pyruvate and reduce it to Lactate. The 6 ATPs produced by 2 NADH2 will not be formed.
4 ATPs are produced at the substrate level (2 ATPs by each triose) by Phosphoglycerate Kinase and Pyruvate Kinase.
2 ATPs are utilized (1 ATP is utilized by Hexokinase/Glucokinase and 1 ATP is utilized by Phosphofructokinase).
The net calculation will be 4 ATPs (at the substrate level) - 2 ATPs (utilized in the 1st and 3rd reaction) = 2 ATPs.
If glycolysis starts from Glycogen, 1 ATP utilized by Hexokinase/Glucokinase is spared hence only 1 ATP is utilized. In this case, the net ATP gain will be = 3 ATPs.

Clinical Notes on Glycolysis

As Glycolysis is a critical metabolic pathway that converts glucose into energy in the form of ATP and consists of 10 steps, each of which is catalyzed by specific enzymes. Abnormalities or disruptions in any of these steps can lead to several diseases, such as.

a. Pyruvate kinase deficiency

Pyruvate kinase is an enzyme that plays a crucial role in the final step of glycolysis.
Deficiency of this enzyme can lead to a buildup of phosphoenolpyruvate and cause hemolytic anemia, jaundice, and liver damage.
The rate of glycolysis is severely decreased.
Results in the decreased rate of ATP production.
The ATPs are inadequate to maintain the structural integrity of the cell membrane.
RBCs become distorted which are phagocytosed by the cells of the reticuloendothelial system in the spleen resulting in anemia.
Since the spleen has to remove a huge number of distorted RBCs from the circulation, it enlarges hence there will be splenomegaly.

b. Fructose Intolerance

This is a genetic disorder in which the body is unable to process fructose due to the hereditary absence of Aldolase-B.
This leads to a buildup of fructose-1-phosphate (hence decreasing the availability of Phosphate), which can disrupt the glycolytic pathway and cause liver damage, hypoglycemia, and other health problems.
Since the phosphate stores are depleted due to abnormal accumulation of Fructose 1-Phosphate, both pathways i.e. Glycogenolysis and Gluconeogenesis may be blocked.
Depletion of Phosphate also decreases substrate-level phosphorylation of ADP resulting in reduced ATP production from ADP + Pi.

c. Galactosemia

This is an inherited disorder in which the body is unable to process galactose, a type of sugar found in dairy products.
This leads to an accumulation of galactose-1-phosphate, which can disrupt the glycolytic pathway and cause liver and brain damage.

d. Phosphofructokinase deficiency

This is a rare genetic disorder in which there is a deficiency of the enzyme phosphofructokinase, which is involved in the second step of glycolysis.
This leads to a buildup of fructose-1,6-bisphosphate and a subsequent decline in glucose levels in the blood, resulting in muscle weakness and fatigue.

e. Lactate dehydrogenase deficiency

This is a genetic disorder in which there is a deficiency of the enzyme lactate dehydrogenase, which is involved in the conversion of pyruvate to lactate.
This leads to a buildup of pyruvate and a decline in ATP levels in the blood, resulting in muscle weakness and fatigue.

f. Lactic Acidosis

The elevated level of Lactate (Lactic Acid) in plasma is known as Lactic Acidosis.
It is a life-threatening condition.
Occurs in situations where Oxygen supply to the tissues becomes deficient e.g. in circulatory collapse (Myocardial Infarction, Pulmonary Embolism, Uncontrolled Hemorrhage, Hepatorenal failure, etc).
Decreased Oxygen impairs Oxidative Phosphorylation resulting in decreased ATP production.
To survive, RBCs start anaerobic glycolysis as a backup system for ATP generation.
Decreased Oxygen increases the conversion of Pyruvate to Lactate resulting in Lactic Acidosis.
Blood Lactate can be used to monitor the presence and severity of shock and to monitor the patient's recovery.

Healthcare Professionals Guide to Understanding Glucose Metabolism | Glycolysis