Inorganic Phosphate and its Roles in Cellular Metabolism
Phosphorus, the first chemical element to be identified, was discovered by Hennig Brand in 1669 while searching for the philosopher’s stone in urine. About a century later, Justus von Liebig later identified the importance of inorganic phosphate (Pi) for plant growth.[1] Today, we know that phosphorus, organically and inorganically is important to all life on Earth. Phosphate is the salt form of phosphoric acid.[2] In cellular metabolism, it plays a crucial role in the creation and breakdown of ATP, enzyme activity, and the structure and metabolism in phospholipids.
Pi in ATP and ADP
Adenosine triphosphate is a nucleotide composed of adenine, ribose, and a chain of three phosphate groups. It is made in the mitochondria, a multilamellar organelles, which are organelles that have multiple layers running parallel to each other. The energy stored in ATP is primarily located in the bonds between these phosphate groups. To break the bonds and release the energy, an action called hydrolysis takes place. Hydrolysis adds a water molecule to ATP in order to break off the outermost phosphate of the phosphate group. A process called phosphorylation transfers that broken off phosphate and the energy to the molecule that needed the energy. We are then left with ADP, adenosine diphosphate. ADP can be turned back into ATP through cellular respiration. This process adds a phosphate to ADP.[3]
Pi in the Regulation of Enzyme Activity
Inorganic phosphate plays a regulatory role in controlling enzyme activity. Many enzymes require phosphate groups for their activation. Protein phosphorylation, the addition of phosphate groups to proteins, can activate or deactivate enzymes, thus regulating their activity. This process
is essential for coordinating cellular metabolism and signaling pathways, allowing cells to respond to internal and external stimuli appropriately.[4]
Pi in Phospholipid structure and metabolism
Phosphate is a key building block for phospholipids, which form cell membranes.[1] Phospholipids are composed of two fatty acid chains or tails, and a phosphate group at the head, joined by an alcohol molecule.[5] The head is hydrophilic or “water loving” and the tails are hydrophobic or “water fearing”. The cell membrane is composed of two layers of phospholipids. The heads face outwards while the tails face inwards. This structure creates a stable barrier between cells and the surrounding outside.
Phospholipid metabolism is the creation, modification, and breakdown of phospholipids. Inorganic phosphate is involved in these metabolic pathways as a substrate for the synthesis of new phospholipids and as a product of phospholipid breakdown. Most phospholipids are made in the endoplasmic reticulum (ER). The first step to make a phospholipid is to make phosphatidic acid.[6] The next step depends on the type of phospholipid. Phospholipids can undergo remodeling processes involving the exchange of fatty acids or head groups. These modifications are crucial for maintaining membrane integrity, fluidity, and functionality.[7] The breakdown of phospholipids is caused by enzymes known as Phospholipases. This process releases fatty acids and other lipid-derived molecules.
[1] Wagner, C. The Basics of Phosphate Metabolism. 2023; National Library of Medicine, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10828206/
[2] Madhusha. Difference Between Organic and Inorganic Phosphate. 2017; PEDIAA, https://pediaa.com/difference-between-organic-and-inorganic-phosphate/#Inorganic%20Phosphate
[3] Petruzzello, M. Adenosine Triphosphate. 2024; Britannica, https://www.britannica.com/science/adenosine-triphosphate
[4] Nestler EJ, Greengard P. Protein Phosphorylation is of Fundamental Importance in Biological Regulation. In: Siegel GJ, Agranoff BW, Albers RW, et al., editors. Basic Neurochemistry: Molecular, Cellular and Medical Aspects. 6th edition. Philadelphia: Lippincott-Raven; 1999. Available from: https://www.ncbi.nlm.nih.gov/books/NBK28063/
[5] Wikipedia Contributors. Phospholipid 2024; https://en.wikipedia.org/wiki/Phospholipid
[6] Cockcroft, S. Mammalian Lipids: Structure, Synthesis and Function. 2021; National Library of Medicine, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8578989/
[7] Wang, B., Tontonoz, P. Phospholipid Remodeling in Physiology and Disease. 2020; National Library of Medicine, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7008953/