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Our superfast human brain and brilliant senses would be nothing without muscles. Every action -- walking, talking, blinking, or so much as thinking -- requires a certain muscle to carry out our will. But what fuels this important part of our body? Adenosine Triphosphate (ATP). Molecules of this essential substance are often referred to as "currency of energy." Though we have several sources of energy in our body, ATP is the only one that is directly usable by any part, muscle, or cell!

ATP: Adenosine Triphosphate
Empirical Formula C10H16N5O13P3
Chemical Formula C10H8N4O2NH2(OH2)(PO3H)3H
Molecular Mass 507.18 g.mol-1

How Much ATP do We Need?
Every second, our body is consuming, spending, and synthesizing ATP in mass volumes. The important thing about this miraculous molecule is that it is never 'created' in our body; it is only recycled or resynthesized. What does that mean? It means that if we had 10 moles of ATP, we could synthesize ten more, only after consuming the initial lot. So, our body is constantly striking a balance between the amount it blows up and the amount it has stored in. The catch is, we store around 50 grams of it, while we end up spending and recycling enough to match our own body weight (in a day)!

Structure of an ATP Molecule

If you're well-versed with organic chemistry, then you'll probably agree that the structure of an ATP molecule is no biggie. Instead of looking at it like a big molecule, break it down into three smaller parts; that way, it's easier understood and quicker learned!

ATP structure

Ribose
The pentagon-shaped structure in the molecular diagram, made up of Carbon, Hydrogen, and Oxygen is the core of an ATP molecule. It is basically, a sugar molecule and resembles a form of fructose.

Adenine Base
Ribose is linked to a purine derivative known as "Adenosine", which is the nitrogenous base in ATP.

Why is It Called a Base?
If you observe the nitrogenous structure, it has two rings (comprising nitrogen) connected at the center; one is a pentagon, while the other is a hexagon. Such a structure is said to be a base; the name 'nitrogenous base' arises owing to the presence of nitrogen.

Why is it called Purine?
Imagine two rings of carbon fused together. One of the rings has five atoms, while the other has six, and each of these rings has two nitrogen atoms. Any compound belonging to this group is known as a purine. Purines are the building blocks of our DNA and several other important compounds.

Chain of Phosphates
Three phosphates are linked together in a single chain, and this chain is connected to the ribose structure. Note that the name "Triphosphate" arises due to the number of phosphates present.

How Does ATP Give Energy?

To understand energy synthesis in our metabolism, understanding three key molecules -- AMP, ADP, and ATP is essential.

AMP - Adenosine Monophosphate
ADP - Adenosine Diphosphate
ATP - Adenosine Triphosphate

» The prefix to 'phosphate' varies with the number of phosphate groups present in the molecule.
» Therefore, AMP comprises one phosphate group, while ADP comprises two and ATP comprises three.

Why is ATP So Important?
» It is the only source of energy in our body that is directly usable!
» Hence, any form of nutrition intake needs to be converted to ATP before our body can utilize it for other functions.

How does ATP Produce This Usable Energy?
Energy in our body is synthesized from an exothermic reaction. Exothermic reaction = Reaction that releases energy.

» An ATP molecule consists of three phosphate groups linked together.
» Under certain conditions, this molecule can lose one or two phosphate groups.
» The reaction wherein a phosphate bond is broken is an exothermic reaction.
» When the first phosphate bond is broken, a high amount of energy is released. This energy is directly usable in our body for carrying out different functions.

ATP + H2O → ADP + Pi + Energy (Δ G = -30.5 kJ.mol-1)
ATP + H2O → AMP + PPi + Energy (Δ G = -45.6 kJ.mol-1)


Note: Observe that the free energy gained from converting ATP to ADP is more than that of converting ATP to AMP. Thus, we can say that the conversion to AMP is beneficial, but not as beneficial as its conversion to ADP.

Inverse of these reaction is also true, that is:

ADP + Pi + Energy → ATP + H2O ..........(1)
AMP + PPi + Energy → ATP + H2O

Though, here the reactions are endothermic.

So if energy is required to resynthesize ATP, then how are we left with any free energy?
» There are several sources of energy in our body; however, only ATP is directly usable to us.
» Thus, energy released from other reactions is utilized to resynthesize ATP.

The Phosphocreatine System

» Phosphocreatine is a high-energy compound.
» This system supplies instantaneous energy for a short duration.
» Like ATP, it can lose its phosphate group in an exothermic reaction to release energy.

Phosphocreatine → Creatine + P + Energy _____(2)
Enzyme: Creatine Kinase (Exothermic reaction)

» So, now we have extra energy and a phosphate group lying around.
» Once your body utilizes an ATP molecule for energy, you are left with an ADP molecule as a residue.
» Thus, this extra phosphate will bond with the available ADP, with the help of energy created in reaction (2) to synthesize ATP.

ADP + Pi + Energy → ATP + H2O _____(1)

Collectively:

» Reactions (1) and (2) are a 'coupled reaction'. Two reactions are said to be coupled when the energy generated by one is applied to complete the other.
» ATP and phosphocreatine levels comprise the Phosphagen system.

In this way, the ATP is recycled time and over again with the help of the phosphocreatine system.

» It is important to remember that this system is not a permanent solution for depleting energy.
» When your muscles are exerted, the level of phosphocreatine begins to decline swiftly.
» Therefore, the phosphagen system is more like a power pack; it will rev your muscles up to the maximum but will last you a few seconds (10 seconds) at the most.

Glycolysis

Glycolysis is a process where glucose undergoes a series of reactions to release 2 ATP of energy. Glycolysis is said to be of two types:

» Aerobic Glycolysis
» Anaerobic Glycolysis


The major process and reactions remain the same in both these types. The image and table provided below lists the common steps and equations for both:

Glycolysis Cycle

No. Reaction ATP
1 glucose → glucose 6-phosphate (-1)
2 glucose 6-phosphate → fructose 6-phosphate --
3 fructose 6-phosphate → fructose 1,6-biphosphate -1
4 fructose 1,6-biphosphate → glyceraldehyde-3-phosphate + dihydroxyacetone phosphate --
- dihydroxyacetone phosphate → glyceraldehyde-3-phosphate --
5 glyceraldehyde-3-phosphate → 1,3-biphosphoglycerate --
6 1,3-biphosphoglycerate → 3-phosphoglycerate 2 x (+1)
7 3-phosphoglycerate → 2-phosphoglycerate --
8 2-phosphoglycerate → phosphoenolpyruvate --
9 phosphoenolpyruvate → pyruvate 2 x (+1)
Net ATP Gain (+2)

Note: These equations aren't chemically complete, or balanced, i.e., byproducts, enzymes, etc., are not included in the same. They are merely listed for better understanding of the cycle.

Why is ATP multiplied by 2?
» Note that at step 5, we had 2 molecules of glyceraldehyde-3-phosphate (as dihydroxyacetone phosphate also converted to glyceraldehyde-3-phosphate with the help of an enzyme).
» Thus, the amount of ATP molecules are multiplied by 2 everywhere thereafter.
» The Krebs Cycle begins with pyruvate, and as we have two molecules of pyruvate here, the net ATP gain there will also be multiplied by 2.

After glucose is converted to pyruvate:-

» If air is absent - Anaerobic Glycolysis

NADH (produced at reaction V) reduces pyruvate to lactate.
» If air is present - Aerobic Glycolysis

NADH proceeds to the electron transport chain for re-oxidization.

The Lactic Acid Cycle

Anaerobic/Fast Glycolysis

» When a muscle is rigorously exerted, it uses up all the available oxygen.
» Muscles are always stocked up on glucose, which is stored in the form of glycogen. (One molecule of glycogen has several molecules of glucose packed together.)
» So, when a muscle requires energy, it breaks off a glucose molecule and uses it to form ATP by converting it to pyruvate.
» In the absence of oxygen, this pyruvate turns into lactate (lactic acid) due to the enzyme 'lactate dehydrogenase'.
» The conversion of glucose to ATP here takes several reactions, and thus this system is relatively slower than that of phosphocreatine.
» Phosphocreatine fuels our muscles for a few seconds, whereas lactic acid system can power it for few minutes!

Lactic Acid System

Why is It Useful?
Most of us wonder why any part of our body would require an 'anaerobic system' for energy generation. The answer is simple; try to recollect the last time you were chased by a dog! If you could remember clearly, you'd know that you sprinted your best in the first couple of seconds and then your heart rate picked up. In intense situations, our body doesn't have time to coordinate breathing and heart rate. Here, we require an instant spur of energy before we can lapse into the aerobic system.

Downfall of the Lactate System
» All of us can relate to that stinging and burning sensation in our muscles when we overwork any part of our body.
» The substance that causes the sting is Lactic Acid.
» As a result, we can only draw up to a certain limit of energy from this system before it wears us out.

The Aerobic System

While the other two systems provide energy instantaneously, the human body works mostly on aerobic respiration. If you're exerting a certain muscle, the phosphocreatine system lasts you a few seconds and the lactic acid system stretches till a couple of minutes. However, by the end of 2 minutes or so, the aerobic system kicks in.

What is the Aerobic System?
Aerobic system or respiration is a process where glucose is broken down in the presence of oxygen to release energy in the form of ATP molecules.

Where Do Cells Get Glucose From?
» Glycogen stored in the muscles
» Glycogen stored in the liver (transported through bloodstream)
» From food ingested (absorbed from intestine and transported through bloodstream)
» Fats stocked in your body (if you are short on carbohydrates)
» Proteins available in your body (if you are short on carbohydrates and fats)

The aerobic system synthesizes ATP from a series of interdependent reactions. As a result, it is the slowest of the three systems. However, it is the most durable as it can fuel your body for hours at a stretch.

Aerobic respiration has three different ATP synthesizing processes, namely (1) Glycolysis, (2) Citric Acid cycle and (3) Electron Transport Chain.

Citric Acid Cycle

Tricarboxylic Acid Cycle/Krebs Cycle/Szent-Györgyi-Krebs cycle

» The citric acid cycle takes place in the matrix of the mitochondrion.
» A series of reactions that occur for ATP synthesis in the second stage of the aerobic system comprise this cycle.
» It is a recurring cycle, i.e., every time, by the end of the cycle, oxaloacetate is regenerated.

Krebs Cycle

Citric Acid Cycle Steps
Sr. No. Reaction ATP NADH
1 Pyruvate → Acetyl CoA - NAD+ → NADH
2 Oxaloacetate + Acetyl CoA → Citrate - -
3 Citrate → cis-Aconitate - -
4 cis-Aconitate → Isocitrate - -
5 Isocitrate → Oxalosuccinate - -
6 Oxalosuccinate → α-Ketoglutarate - NAD+ → NADH
7 α-Ketoglutarate → Succinyl-CoA - NAD+ → NADH
8 Succinyl-CoA → Succinate (+1) -
9 Succinate → Fumarate - -
10 Fumarate → L-Malate - -
11 L-Malate → Oxaloacetate - NAD+ → NADH
12 Oxaloacetate → Citrate - -
Net ATP Gain 2 x (+1)

Note: These equations aren't chemically complete or balanced, that is, byproducts, enzymes, etc., are not included in the same. They are merely listed for better understanding of the cycle.

Electron Transport Chain

ETC

Complex I: NADH-CoQ oxidoreductase

Contains - FeS, FMN, Coenzyme Q
Inhibitors - Rotenone

NADH + CoQ + H+ → NAD+ + CoQH2
(NADH and H+ enter the ETC)

Activity - NADH reductase
✓ Pumps protons outside the mitochondria
✓ ATP produced
Complex II: Succinate-CoQ reductase

Contains - FeS, Coenzyme Q
Inhibitor - Carboxin

NADH + CoQ + H+ → NAD+ + CoQH2
(Catalyst: succinate dehydrogenase)

Entry Site - FADH2
Activity - FAD reductase
✗ ATP: None
✗ No protons pumped outside

Complex III: CoQH2-cytochrome c oxidoreductase

Contains - cytochrome c, b, C1, and FeS
Inhibitor - Antimycin A

cyt c (ox) + CoQ (red) → CoQ (ox) + cyt c (red)

Activity - Ubiquinone → Oxidation; Cyt C → Reduction
✓ ATP is produced.
✓ Protons are transported outside the mitochondria.
Complex IV: cytochrome oxidase

Contains - Cytochrome a, a3, and Copper
Inhibitor - Cyanide, Azide, Carbon monoxide

cyt c (red) + 2H+ + ½ O2 → cyt c (ox) + H2O

✓ ATP is produced.
✓ Protons are pumped outside the mitochondria.

Complex V (informally): ATP Synthase

Inhibitor - Oligomycin
Activity - Making ATP from ADP and Pi

Total ATP Production

ATP produced from Glycolysis 2
ATP produced from the Citric Acid Cycle 2
ATP produced due to the Electron Transport Chain 32
Net Total 36 ATPs

ATP is a crucial molecule for our metabolism. Not only does it provide us energy, ATP is responsible for an array of other vital functions, like transporting macromolecules in and out of the cell and through the cell membrane, and being an extracellular and intracellular signaling molecule (an important function in both the central and peripheral nervous system).