DIHYDROXYACETONE PHOSPHATE (DHAP): CHARACTERISTICS AND APPLICATIONS - CHEMISTRY - 2025

The phosphate dihydroxyacetone is a chemical compound under the abbreviations abbreviated DHAP. It is an intermediate in some metabolic pathways of living organisms, such as glycolytic degradation or glycolysis, as well as in the Calvin cycle in plants.

Biochemically, DHAP is the product of the action of an aldolase enzyme on fructose-1,6-bisphosphate (FBP), which causes an aldolytic breakdown resulting in two three-carbon compounds: DHAP and glyceraldehyde 3-phosphate (GAP).

Source: David T. Macpherson

In the Calvin cycle, aldolase performs the reverse reaction, condensing DHAP molecules with GAP molecules to form a hexose.

characteristics

DHAP is classified within the molecules known as ketotrioses. These are monosaccharides made up of a chain of three carbons (trioses) with the carbonyl group at the central carbon (C2).

GAP and DAHP are functional isomers and make up the simplest carbohydrates within biologically active organic molecules.

Although the chemical structure of many common carbohydrates such as GAP and DHAP are aldehydes and ketones, they are given the term carbohydrate, referring to direct derivatives of saccharides.

DHAP in glycolysis

In glycolysis a series of reactions degrade glucose to pyruvate. This degradation occurs progressively in 10 consecutive steps, where different enzymes intervene and a variety of intermediates are produced, all of which are phosphorylated.

DHAP appears in glycolysis in the fourth reaction of this process, which consists in the breakdown of FBP into two carbohydrates of three carbons (trioses), of which only GAP continues the sequence of glycolysis, while DHAP needs be transformed into GAP to follow this route.

This reaction is catalyzed by an aldolase (fructose bisphosphate aldolase), which carries out an aldol cleavage between the C3 and C4 carbons of the FBP.

This reaction only occurs if the hexose to be divided has a carbonyl group at C2 and a hydroxyl at C4. For this reason, isomerization of glucose-6-phosphate (G6P) into fructose 6-phosphate (F6P) occurs previously.

DHAP is also involved in the fifth reaction of glycolysis, being its isomerization to GAP by the enzyme triose phosphate isomerase or TIM. With this reaction the first phase of glucose degradation is completed.

Aldolase reaction

In the aldol breakdown, two intermediates are produced, where DHAP makes up 90% of the mixture at equilibrium.

There are two types of aldolases: a) type I aldolase is present in animal and plant cells and is characterized by the formation of a Schiff's base between the enzymatic active site and the carbonyl of the FBP. b) Aldolase type II is found in some bacteria and fungi, it has a metal in the active site (generally Zn).

The aldol cleavage begins with the adhesion of the substrate to the active site and the removal of a proton from the β-hydroxyl group, forming the protonated Schiff's base (iminium cation). The breakdown of the C3 and C4 carbons produces the release of GAP and the formation of an intermediate called enamine.

The enamine is subsequently stabilized, whereby an iminium cation is formed which is hydrolyzed, with which DHAP is finally released and the free enzyme is thus regenerated.

In cells with type II aldolase, the formation of Schiff's base does not occur, being a metallic divalent cation, generally Zn ²⁺, which stabilizes the enamine intermediate in order to release DHAP.

TIM reaction

As mentioned, the equilibrium concentration of DHAP is higher than that of GAP, so that DHAP molecules are being transformed into GAP as the latter is being used in the following glycolysis reaction.

This transformation occurs thanks to the TIM enzyme. This is the fifth reaction of the glycolytic degradation process and in it, the C1 and C6 carbons of glucose become the C3 carbons of GAP, while the C2 and C5 carbons become C2 and C3 and C4 of glucose. they become C1 of the GAP.

The TIM enzyme is considered the "perfect enzyme" because diffusion controls the rate of the reaction, which means that the product is formed just as quickly as the enzyme's active site and its substrate come together.

In the reaction of transformation of DHAP to GAP an intermediate called enediol is formed. This compound is capable of giving up the protons of the hydroxyl groups to a residue of the active site of the TIM enzyme.

DHAP in the Calvin cycle

The Calvin cycle is the photosynthetic carbon reduction (PCR) cycle that constitutes the dark phase of the photosynthesis process in plants. In this stage, the products (ATP and NADPH) obtained in the light phase of the process are used to make carbohydrates.

In this cycle, six GAP molecules are formed, of which two are transformed into DHAP by isomerization, thanks to the action of the TIM enzyme, in an inverse reaction to that which occurs in the degradation of glycolysis. This reaction is reversible, although the equilibrium, in the case of this cycle and, unlike glycolysis, is shifted towards the conversion of GAP to DHAP.

These DHAP molecules can then follow two pathways, one is an aldol condensation catalyzed by an aldolase, in which it condenses with a GAP molecule to form FBP.

The other reaction that one of the DHAPs can take is a phosphate hydrolysis catalyzed by a sedoheptulose bisphosphatase. In the latter route, it reacts with an erythrose to form sedoheptulose 1,7-bisphosphate.

DHAP in gluconeogenesis

In gluconeogenesis some non-glucidic compounds such as pyruvate, lactate and some amino acids are converted into glucose. In this process, DHAP appears again through the isomerization of a GAP molecule by the action of TIM, and then through an aldol condensation, it becomes FBP.

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