Glycolysis, Lactic Acid & Muscle Fatigue

How our cells create energy with Oxygen and Glucose and the dangers of Lactic Acid buildup

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You just crushed out an awesome workout — your heart rate was up, blood was pumping and you definitely burned some calories along the way.

You get a good night’s rest and the next day you can barely move.

The soreness tells you the workout was a great one.

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Leading a healthy lifestyle requires both food and energy. In order for our body to function properly, we intake molecules vital to our metabolic processes. It’s important not to over-do strenuous activity and our bodies often give us signs to tell us to stop.

The nutrients you intake go through a series of intricate chemical processes to be metabolized into energy. Whether taking a walk or doing an intense workout, our muscles need sufficient amounts of glucose and oxygen to compensate for the work they engage in.

The reactions that extract energy from molecules like glucose are catabolic and break bigger molecules into smaller ones to release energy. When glucose is broken down in the presence of oxygen, it is converted into six carbon dioxide molecules and six water molecules.

As glucose is broken down, much of the energy is released as heat, but some can be captured by adenosine triphosphate (ATP). ATP is the energy currency for our cells, and is stored in the mitochondria.

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You’re going to need to know some terms:

Aerobic respiration: processes that do require oxygen
Anaerobic respiration: processes that do not require oxygen
Phosphorylation: process that involves the addition of phosphate to an organic compound
Isomerization: when a molecule is transformed into a different molecular shape
Substrate level phosphorylation: refers to the phosphorylation of ATP from ADP

Good? Good. Let’s go.

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Majority of the metabolic processes occuring in our body are aerobic, meaning they require oxygen. The oxygen we inhale along with glucose from carbohydrates are the two main molecules needed for aerobic respiration to produce ATP for our cells. When engaging in strenuous exercise, our muscles require much more oxygen to keep up with our metabolic rate increasing. Our heart rate also increases since our blood needs to transport more oxygen to the muscles hard at work. Our body prefers to undergo aerobic processes because the end products are intermediates required for further processes.

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GLYCOLYSIS is one of the first metabolic processes carried out in the body.

Note: Glycolysis is a unique and can proceed with OR without oxygen.

When sufficient oxygen is present, cellular respiration occurs and aerobic glycolysis is carried. If oxygen isn’t present, anaerobic respiration and anaerobic glycolysis is carried out.

If you reverse this reaction, you’d get the reactants and products of photosynthesis!

Aerobic Glycolysis

Here’s an overview of the 10-step process:

It is a 10-step process that occurs in the cytosol of the cell. Here’s what you need to know:

1. Starting material: Glucose — a six-carbon compound
2. Split in half: Glucose is broken down into 2 three-carbon compounds
3. Pyruvate: these 3-carbon compounds are called pyruvate
4. For each glucose molecule, we have 2 pyruvate molecules
5. In the process, 2 molecules of NAD+ gain electrons and are reduced to 2 molecules of NADH
6. 4 ATP are created but 2 are consumed in the process
7. We end up with 2 NADH molecules and 2 ATP molecules

In cells with mitochondria, the pyruvate is decarboxylated by a pyruvate dehydrogenase complex to form Acetyl-CoA that feeds into the Tricarboxylic acid cycle and ultimately participates in ATP production.

1. Once the glucose molecule enters the cell, it is immediately phosphorylated by hexokinase to glucose-6-phosphate. This is an irreversible reaction and acts as a trap to keep glucose within the cell
2. Glucose-6-phosphate (aldose) is isomerized to fructose-6-phosphate (ketose)
3. Fructose-6-phosphate is phosphorylated to fructose-1, 6-bisphosphate. This reaction can be reversible, but requires more energy hence consuming an ATP in the process
4. Fructose-1, 6-bisphosphate is cleaved, resulting in the formation of DHAP (dihydroxyacetone phosphate) and G3P (glyceraldehyde-3-phosphate)
5. Conversion of DHAP and G3P is carried our and we are left with two molecules of G3P
6. The first oxidation-reduction occurs in this step. NAD+ reduces to NADH and G3P is oxidized to a carboxyl group attached to a phosphate group. There are limited amounts of NAD+ and NADH so the cells require the constant oxidation of NAD+ to NADH and the reduction of NADH to NAD+
7. The phosphate group that is attached in the step above is used to phosphorylate ADP, thereby generating ATP
8. 3-phosphoglycerate is isomerized to 2-phosphoglycerate
9. 2-phosphoglycerate is converted into phosphoenolpyruvate
10. Phosphoenolpyruvate goes through substrate level phosphorylation to become pyruvate

Anaerobic Glycolysis

Here’s a quick overview:

• we carry out fermentation — specifically lactate fermentation — in our cells
• without oxygen, our cells run out of NAD+ quickly (we keep using it up to create NADH in glycolysis!)
• using fermentation, our body regenerates NAD+ by taking away electrons and oxidizing NADH, allowing glycolysis to continue
• the pyruvate also reacts with the NADH to re-oxidize it to NAD+ WHILE it’s being converted to lactate

The fact that our cells and body can interpret and adapt is mindblowing! Everything has a chain reaction and is vital for our body to function as a whole.

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Remember, we’d rather go through aerobic respiration as opposed to anaerobic respiration. When there is an insufficient amount of oxygen, our body will start to break down the glucose without oxygen.

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Lactate vs. Lactic Acid

During glycolysis, H+ ions are released in the muscle cell. A higher concentration of H+ ions results in a higher pH level (more acidic). Without oxygen, the H+ cannot be removed and causes the muscle to become increasingly acidic. This is the acidity we feel solely as a result of a high accumulation of hydrogen ions (H+)

Lactate is formed when one molecule of pyruvate attaches to two H+ ions. The lactate is removed from the cell, protecting the cell from becoming too acidic to continue the exercise. However, there will reach a point where the cell won’t be able to remove enough lactate to control the acidosis caused by the rapid accumulation of H+.

Lactic Acid Fermentation

Usually, the pyruvate would travel to the mitochondria to continue into pyruvate oxidization — the next step in aerobic respiration. However, since we’re exercising, our cells require energy production faster than our bodies can adequately deliver oxygen. This is when our body kicks into anaerobic respiration.

Lactic Acid Fermentation is more on recycling pyruvate and NADH as opposed to new ATP synthesis. The pyruvate is used to oxidized NADH to become NAD+ to ensure there is enough NAD+ for glycolysis to begin. In the process of oxidizing NADH, the coupled reaction causes pyruvate (in this case pyruvic acid) to be reduced to lactic acid.

As lactate levels rise above 5 mmol/L, there is an increasing risk of
lactic acidosis, and result in tachycardia (increased heart rate) tachypnea (increased respiratory rate). The main cause of lactic acidosis is when a person overproduces and/or underutilized lactic acid and their body cannot adapt to this change.

This buildup of acid causes an imbalance in pH level, which should always be slightly alkaline instead of acidic. There are a few different types of acidosis.

Lactic acid buildup occurs when there’s not enough oxygen in the muscles to break down glucose.

The next time you exercise, it is important to be aware of the intensity of your activity and your limits. Adequate rest is needed to keep your muscles at a healthy pH level in order to engage in physical activities in the future.

If you enjoyed this article, please shoot me a message on LinkedIn! I am a high school student enthusiastic about the human and plant metabolome and would love some guidance or resources sent my way! Thank you — Emaan :)