GLYCEROL 3-PHOSPHATE: STRUCTURE, CHARACTERISTICS, FUNCTIONS - BIOLOGY - 2025

The glycerol 3-phosphate is a glycerol molecule having an ester bond with a phosphate group, having numerous functions in metabolism and part of biomembranes. This molecule serves as a metabolite for gluconeogenesis, triacylglycerol biosynthesis, and second messenger biosynthesis such as diacylglycerol (DAG).

Other functions of glycerol 3-phosphate are the biosynthesis of glycerophospholipids, such as cardiolipin, plasmallogens, and alkylacylglycerophospholipids. In addition, it participates in a shuttle that allows NAD ⁺ to be regenerated in the cytosol.

Source: Mzaki

Structure and characteristics

The empirical formula of glycerol 3-phosphate is C ₃ H ₉ O ₆ P and it has three carbon atoms. Carbon atoms 1 and 3 (C-1 and C-3) form hydroxymethyl groups (-CH2OH), while carbon atom 2 (C-2) forms a hydroxymethylene group (-CHOH). The oxygen atom of the hydroxymethyl group of C-3 forms an ester bond with a phosphate group.

There are synonyms for glycerol 3-phosphate, such as 1,2,3-propanetriol, 1- (dihydrogen phosphate) and 2,3-dihydroxypropyl dihydrogen phosphate, 3-phosphoglycerol. Its molecular weight is 172.07 g / mol.

The standard Gibbs free energy change (ΔGº) from hydrolysis of the phosphate group of glycerol 3-phosphate is -9.2 KJ / mol.

This metabolite is converted into an intermediate of glycolysis. When the cellular energy load is high, the flow through glycolysis is diminished and dihydroxyacetone phosphate (DHAP) serves as a starting material for the biosynthetic pathways.

Features

Gluconeogenesis and the pentose phosphate pathway

Glycerol serves as a metabolite for the anabolic pathways. For this, it must be converted into a glycolytic intermediate through two steps that require the enzymes glycerol kinase and glycerol phosphate dehydrogenase to form the dihydroxyacetone-phosphate intermediate (DHAP).

The enzyme glycerol kinase catalyzes the transfer of a phosphate group from ATP (adenosine triphosphate) to glycerol, forming glycerol 3-phosphate and ADP (adenosine diphosphate). Next, glycerol 3-phosphate dehydrogenase catalyzes an oxidation-reduction reaction, in which the C-2 of glycerol 3-phosphate is oxidized, losing two electrons.

The electrons from glycerol 3-phosphate (reduced) are transferred to NAD ⁺ (oxidized), forming DHAP (oxidized) and NADH (reduced). DHAP is an intermediate metabolite of glycolysis that provides carbon skeletons for anabolic pathways, such as glycogen and nucleotide biosynthesis.

Glucose 6-phosphate formed by gluconeogenesis can proceed to glycogen biosynthesis or to the pentose phosphate pathway. During glycogen biosynthesis in the liver, glucose 6-phosphate is converted to glucose 1-phosphate. During the pentose phosphate pathway, glucose 6-phosphate is converted to ribose 5-phosphate.

Triacylglycerol biosynthesis

Triacylglycerols are neutral (uncharged) lipids that possess fatty acid esters covalently bound to glycerol. Triacylglycerols are synthesized from fatty acyl-CoA esters and glycerol 3-phosphate or DHAP.

Glyceroneogenesis is the new biosynthesis of glycerol from oxaloacetate, using gluconeogenesis enzymes. Pyruvate carboxylase converts pyruvate to oxaloacetate, and phosphoenolpyruvate carboxykinase (PEPCK) converts oxaloacetate to phosphoenolpyruvate, a glycolytic intermediate.

Phosphoenolpyruvate continues the gluconeogenesis pathway towards the biosynthesis of DHAP, which is converted to glycerol by glycerol 3-phosphate dehydrogenase and a phosphatase that hydrolyzes the phosphate group. The glycerol thus formed is used for the biosynthesis of triacylglycerols.

During periods of starvation, 30% of the fatty acids that enter the liver are reesterified to triacylglycerols and exported as very low-density lipoproteins (VLDL).

Although adipocytes do not carry out gluconeogenesis, they possess the enzyme phosphoenolpyruvate carboxykinase (PEPCK), which participates in the glycerolgenesis necessary for triacylglycerol biosynthesis.

Common glycerophospholipids

Glycerophospholipids are glycerol 3-phosphate triesters, in which the phosphate is the polar head. C-1 and C-2 form ester bonds with saturated fatty acids, such as palmitate or sterate, and a monounsaturated fatty acid, such as oleate. This description corresponds to phosphatidate, which is the simplest glycerophospholipid.

In eukaryotic cell membranes, phosphatidate serves as a precursor for the more common glycerophospholipids, which are phosphatidylcholine, phosphatidylserine, phosphatidylethanolamine, and phosphatidylinositol.

The distribution of lipids (glycerophospholipids, sphingophospholipids, sphingoglycolipids, cholesterol) in cell membranes is not uniform. For example, the inner monolayer of the erythrocyte membrane is rich in glycerophospholipids, while the outer monolayer is rich in sphingolipids.

Glycerophospholipids are important because they participate in cell signaling. Through the action of phospholipase enzymes, such as phospholipase C, which breaks the ester bond at the C-3 level of phosphatidylinositol-4,5-bisphosphate (PPI2), the signaling molecules inositol 1,4,5-triphosphate and diacylglycerol (DAG).

Often, snake venoms contain phospholipase A2 enzymes, which break down glycerophospholipids. This causes tissue damage by rupturing the membranes. The fatty acids released act as detergents.

Less common glycerophospholipids

The membranes of eukaryotic cells contain other phospholipids such as cardiolipin, plasmalogens and alkylacylglycerophospholipids.

Cardiolipin is a phospholipid that was first isolated from heart tissue. Its biosynthesis requires two phosphatidylglycerol molecules. Plasmalogens contain hydrocarbon chains linked to glycerol C-1 by a vinyl ether bond. In mammals, 20% of glycerophospholipids are plasmallogens.

In alkylacylglycerophospholipids an alkyl substituent is attached to the C-1 of glycerol by ether linkage. These glycerophospholipids are less abundant than plasmalogens.

NAD regeneration

The skeletal muscle, brain, and muscle of flying insects use the glycerol 3-phosphate shuttle. Glycerol 3-phosphate consists mainly of two isoenzymes: glycerol 3-phosphate dehydrogenase and a flavoprotein dehydrogenase.

Glycerol 3-phosphate dehydrogenase catalyzes the oxidation of cytosolic NADH. This NADH is produced in glycolysis, in the step catalyzed by glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Glycerol 3-phosphate dehydrogenase catalyzes the transfer of two electrons from NADH (reduced) to the dihydroxyacetone phosphate substrate (oxidized).

The products of the catalysis of glycerol 3-phosphate dehydrogenase are NAD ⁺ (oxidized) and glycerol 3-phosphate (reduced). The latter is oxidized by a flavoprotein dehydrogenase found in the inner membrane of the mitochondria. In this way, DHAP is recycled.

Flavoprotein dehydrogenase gives up electrons to the electron transport chain. Because of this, the NADH in the cytosol serves for the biosynthesis of 1.5 ATP molecules by oxidative phosphorylation in the electron transport chain. The regeneration of NAD ⁺ in the cytosol allows glycosis to continue. GAPDH uses NAD ⁺ as a substrate.

References

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