Glycolysis Pathway: Energy Production and Pyruvate Fate

Glycolysis: Breakdown of Glucose

Preparatory Phase (Energy Investment)

This initial phase requires the cell to invest energy by spending two ATP molecules to phosphorylate glucose. First, glucose is phosphorylated, and then fructose-6-phosphate undergoes phosphorylation. These phosphate transfers are catalyzed by transferase enzymes, specifically kinases, which transfer phosphate groups from ATP.

1. An isomerase enzyme converts glucose-6-phosphate into a ketose, fructose-6-phosphate.
2. Fructose-6-phosphate is phosphorylated again by a kinase, using another ATP, forming fructose-1,6-bisphosphate.
3. Fructose-1,6-bisphosphate is then cleaved into two different 3-carbon phosphorylated isomers: glyceraldehyde-3-phosphate (G3P) and dihydroxyacetone phosphate (DHAP).
4. Depending on cellular requirements, these two isomers can be interconverted by the enzyme triose phosphate isomerase. When the cell requires more energy production, dihydroxyacetone phosphate (DHAP) is converted into glyceraldehyde-3-phosphate (G3P) by this isomerase.

Payoff Phase (Energy Generation)

In this phase, the initial investment of two ATP molecules is recovered, and an additional four ATP molecules are synthesized, resulting in a net gain of two ATP per glucose molecule through glycolysis. Furthermore, this stage reduces two molecules of the coenzyme NAD⁺ to form two molecules of (NADH + H⁺), and synthesizes two molecules of pyruvic acid.

1. Two molecules of glyceraldehyde-3-phosphate (G3P) are oxidized (dehydrogenated) by glyceraldehyde-3-phosphate dehydrogenase. This enzyme uses NAD⁺ as its coenzyme and incorporates an inorganic phosphate (P_i) molecule. This results in the formation of two molecules of 1,3-bisphosphoglycerate.
2. A phosphoglycerate kinase transfers a high-energy phosphate group from each 1,3-bisphosphoglycerate molecule to ADP, forming ATP. This step produces two ATP molecules (recovering the initial investment) and two molecules of 3-phosphoglycerate.
3. The two molecules of 3-phosphoglycerate are converted into 2-phosphoglycerate by the action of an isomerase (specifically, phosphoglycerate mutase).
4. An enolase enzyme removes a water molecule from each 2-phosphoglycerate molecule, converting them into two molecules of phosphoenolpyruvate (PEP).
5. A pyruvate kinase, requiring Mg⁺² and Mn⁺² ions, catalyzes the transfer of the phosphate group from each PEP molecule to ADP. This substrate-level phosphorylation yields two more ATP molecules. The two PEP molecules are converted into two molecules of pyruvic acid (2 CH₃-CO-COOH).

Fate of Pyruvic Acid

Anaerobic Conditions

In the absence of oxygen (anaerobic conditions), cells carry out fermentations or incomplete respiration. The end product is an organic compound that is not fully degraded. Fermentations typically yield only about 5% of the energy that would be obtained from complete aerobic respiration.

Aerobic Conditions

In aerobic cells (typically eukaryotic cells with mitochondria), the pyruvic acid produced by glycolysis enters the mitochondrial matrix. Here, it is further degraded. It undergoes decarboxylation (loss of CO₂) and dehydrogenation (oxidation) catalyzed by the pyruvate dehydrogenase complex. This process requires the resulting acetyl group to attach to Coenzyme A (CoA), forming Acetyl-CoA, a central molecule in metabolism.

Coenzyme A is a complex nucleotide composed of:

• Adenine linked to beta-D-ribose via an N-glycosidic bond.
• Two phosphate groups attached to carbon 5 of the ribose.
• These phosphates are linked to a molecule of Vitamin B5 (pantothenic acid).
• Vitamin B5 is coupled to the amino acid cysteine.
• The crucial functional part is the terminal sulfhydryl (-SH) group of cysteine, which binds to the acetyl group to form Acetyl-CoA.