MCAT Organic Chemistry Review

Nitrogen- and Phosphorus-Containing Compounds

10.3 Phosphorus-Containing Compounds

Phosphoric acid is an extremely important molecule biochemically. This molecule forms the high-energy bonds that carry energy in adenosine triphosphate (ATP).

DESCRIPTION

In a biochemical context, phosphoric acid is sometimes referred to as a phosphate group or inorganic phosphate, denoted Pi. At physiological pH, inorganic phosphate includes molecules of both hydrogen phosphate (HPO42−) and dihydrogen phosphate (H2PO4).

In addition to the energy-carrying nucleotide phosphates, phosphorus is also found in the backbone of DNA in phosphodiester bonds linking the sugar moieties of the nucleotides, as shown in Figure 10.9.

Figure 10.9. Phosphodiester Bond in DNA

When a new nucleotide is joined to a growing strand of DNA by a DNA polymerase, it releases an ester dimer of phosphate, referred to as pyrophosphate (P2O74−), denoted PPi, and shown in Figure 10.10. The hydrolytic release of this molecule provides the energy for the formation of the new phosphodiester bond. Pyrophosphate is unstable in aqueous solution and is hydrolyzed to form two molecules of inorganic phosphate, which can then be recycled to form high-energy bonds in ATP or for other purposes.

Figure 10.10. Pyrophosphate Anion

BRIDGE

DNA replication is an important process for the MCAT. Nucleotide triphosphates are added to the growing daughter strand, with the release of pyrophosphate, PPi. The process of DNA synthesis is described in Chapter 6 of MCAT Biochemistry Review.

Nucleotides, such ATP, GTP, and those in DNA, are referred to as organic phosphates due to the presence of the phosphate group bound to a carbon-containing molecule.

PROPERTIES

Phosphoric acid is unique in that it has three acidic hydrogens, each with its own pKa. Phosphoric acid most properly refers to the form that predominates in strongly acidic conditions, H3PO4. In mildly acidic conditions, it loses a proton to become dihydrogen phosphate, H2PO4; it will readily lose a second proton to become hydrogen phosphate, HPO42−; in weakly basic solutions. The form that exists in strongly basic solutions is phosphate, PO43−. The pKa for the loss of the first hydrogen is 2.15; for the second, 7.20; and for the third, 12.32. At a physiological pH of 7.4, this means that dihydrogen phosphate and hydrogen phosphate predominate in nearly equal proportions. This variety of pKa values also makes phosphates good buffers because they can pick up or give off protons depending on the pH of the solution.

KEY CONCEPT

Phosphoric acid is an excellent buffer because it has three hydrogens with pKa values that span nearly the entire pH scale.

Adjacent phosphate groups on a nucleotide triphosphate experience a large amount of repulsion because they are negatively charged. This, combined with the ability of phosphate to stabilize up to three negative charges by resonance, means that the energy released when a phosphate or pyrophosphate is cleaved is quite high. These reactions are therefore effectively irreversible.

MCAT Concept Check 10.3:

Before you move on, assess your understanding of the material with these questions.

1.    What characteristics make inorganic phosphate so useful for energy transfer biologically?

2.    What is an organic phosphate?

3.    What characteristics of phosphoric acids make them good buffers?