ATP Biosynthesis

Adenosine triphosphate (ATP) is a high-energy molecule present in living cells. It is a nucleoside triphosphate that provides energy within cells for metabolism and is used in several cellular processes including the synthesis of key biomolecules.

ATP is typically present in cells at a concentration of 1-10mM – it is continuously recycled in organisms to ensure there is a constant energy supply for cellular processes.

ATP can be synthesized by redox reactions that use simple and complex lipids or carbohydrates as the source of energy. Complex energy sources need to be digested into simpler molecules before being used in ATP synthesis. Complex carbohydrates are usually hydrolyzed into glucose and fructose, while triglycerides are metabolized to form glycerol and fatty acids.

The biosynthesis of ATP by oxidative phosphorylation and photophosphorylation is the fundamental pathway for energy production in animals, plants, and microbes. Eukaryotic ATP production usually takes place in the mitochondria of the cell.

Important pathways by which eukaryotes generate energy are glycolysis, the citric acid cycle (or the Kreb’s cycle), and the electron transport chain (or the oxidative phosphorylation pathway).

Together these 3 stages are referred to as cellular respiration. In human beings, cellular respiration converts adenosine diphosphate (ADP) to ATP and thus releases energy from molecules that are rich in energy.

ATP synthesis

Glycolysis

Glycolysis involves the metabolization of glucose and glycerol to form pyruvate. These reactions take place in the cytoplasm in most organisms and release a net amount of 2 ATPs. Here glucose is converted to pyruvate via phosphorylation with the help of 2 key enzymes - phosphoglycerate kinase and pyruvate kinase.

The overall reaction can be represented as below:

Glucose + 2 NAD+ + 2 ADP + 2 Pi à 2 Pyruvate + 2 NADH + 2 H+ + 2 ATP + 2 H2O

Thus each molecule of glucose undergoes glycolysis to give 2 pyruvates. Two reduced nicotinamide adenine dinucleotide (NADH) molecules and 2 water (H2O) molecules are also produced as a result of glycolysis. The NADH molecules are oxidized in the electron transport chain to produce ATP and the pyruvate produced is used a substrate for the Kreb’s cycle.

Kreb’s cycle

The Kreb’s cycle is also known as the tricarboxylic acid (TCA) cycle and occurs in the mitochondria. It involves a series of reactions by which pyruvate is degraded into CO2, ATP, water, and electrons.

Pyruvate produced by glycolysis in the cytoplasm gets converted to acetyl-Coenzyme A (acetyl-CoA) in the mitochondria. The acetyl-CoA is converted into citrate which then undergoes a series of series of redox, hydration, dehydration, and decarboxylation reactions to form isocitrate, alpha-ketogluterate, succynl-CoA, fumerate, and malate.

These reactions are catalyzed by several key enzymes in the pathway such as citrate synthase, aconitase, isocitrate dehydrogenase, and malate dehydrogenase. Overall, the Kreb’s cycle yields 2 ATP molecules, 6 NADH molecules, and 2 reduced flavin adenine dinucleotide (FADH2) molecules.

Acetyl-CoA derived from the metabolism of carbohydrates, fats, and proteins in cells is all used in the Kreb’s cycle to generate energy. Therefore, this is an important metabolic pathway that unites carbohydrate, fat, and protein metabolism in living organisms.

NADH and FADH2 molecules generated as byproducts of the citric acid cycle are fed into the electron transport chain where they are oxidized to produce ATP with the help of the enzyme ATP synthase. This enzyme is present in the mitochondria and catalyzes the production of ATP by combining ADP and inorganic phosphate.

ATP synthase is often referred to as a complex molecular machine which has central rotor that moves at a speed of 150 rotations/s during ATP synthesis.

In total, each glucose molecule undergoing cellular respiration produces 38 ATP molecules – 2 ATPs from glycolysis, 2 ATPs from the Kreb’s cycle, and 34 ATPs from the electron transport chain.

References

  1. http://www.ncbi.nlm.nih.gov/pubmed/11997128
  2. http://www.ncbi.nlm.nih.gov/pubmed/12745923
  3. https://www.ncbi.nlm.nih.gov/pubmed/11997128

Last Updated: Feb 26, 2019

Susha Cheriyedath

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Susha Cheriyedath

Susha has a Bachelor of Science (B.Sc.) degree in Chemistry and Master of Science (M.Sc) degree in Biochemistry from the University of Calicut, India. She always had a keen interest in medical and health science. As part of her masters degree, she specialized in Biochemistry, with an emphasis on Microbiology, Physiology, Biotechnology, and Nutrition. In her spare time, she loves to cook up a storm in the kitchen with her super-messy baking experiments.

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Comments

  1. Kathy Krishnan Kathy Krishnan United States says:

    In textbooks people claim that conversion of ADP to ATP as the biosynthesis of ATP using ATP synthase. IMHO, it is NOT ATP synthesis! It is just a phosphorylation reaction carried out by ATP synthase. ADP is recycled to ATP by adding phosphate group.

    How ATP is in fact biosynthesised?

    Let us see How Cholesterol is biosynthesised? You start from Acetyl-CoA and go on build every carbon present in cholesterol to biosynthesise Cholesterol using intermediates such as isoprenyl pyrophosphate and dimethyl allyl pyrophosphate and squalene and Lanosterol. Because it is a "de novo"  synthesis you need to start from simplest "piece" of carbon source and go on build the whole cholesterol molecule. Because it is a "de novo" synthesis you should NEVER EVER  use "cholesterol" as a catalyst to make cholesterol itself. The reason is that "Where does that "cholesterol" come from cant be justified.
    Now, let us look at biochemistry books of de novo ATP synthesis starting from simple amino acids and go on cyclize it to for the "base skeleton" required for ATP.(rather AMP or ADP). In every synthesis reported in standard text books, they USE ATP itself to carry out the cyclization. Here is where I find it funny. Because YOU CAN NOT USE ATP to make ATP- it is as simple as that. Because the question arises "Where the heck that "ATP" come from?" Nobody seems to care about this flaw in biosynthesis of ATP! I have not seen any de novo atp synthesis without using atp itself as a "catalyst"! And again making ATP from ADP is not synthesis. ATP synthase is just an "recycling machine" by adding "phosphate group" that's all!

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