Carbohydrate Metabolism

Glycolysis Defined as the Sequence of Reactions Converting Glucose to Pyruvate or Lactate, and the Production of ATP.

The complete pathway of glycolysis was elucidated in 1940

It is commonly referred to as the Embden-Meyerhof pathway (EMP Pathway).

Salient Features:

1.The enzymes of this pathway are present in the cytosol of the cell.

2.Glycolysis occurs in two forms:

– Anaerobic (in the absence of oxygen produce lactate)

– Aerobic (in the presence of oxygen produce pyruvate)

3.Glycolysis is the major pathway for ATP synthesis in cells lacking mitochondria, e.g., erythrocytes, cornea, lens, etc.

Glucose + 2 ADP + 2 Pi → 2 Lactate + 2 ATP

4.Glycolysis is a central metabolic pathway, with many of its intermediates providing building blocks for other pathways.

5.Reversal of glycolysis, along with alternate pathways at certain steps, allows for the synthesis of glucose (gluconeogenesis).

Phases of Glycolysis:

1.Priming Stage or Energy Investment Phase:

– G3P is oxidized and phosphorylated, yielding molecules of 1,3-bisphosphoglycerate (1,3-BPG) and generating ATP.

2.Splitting Phase:

– Glucose is phosphorylated and split into two molecules of glyceraldehyde-3-phosphate (G3P).

3. Energy Generation Phase:

– ATP is produced through substrate-level phosphorylation, and pyruvate or lactate is formed as the final product.

Glycolysis is a fundamental pathway in cellular metabolism, converting glucose into energy-rich molecules under both aerobic and anaerobic conditions. Its intermediates play crucial roles in various metabolic processes, making it a central focus of biochemical study.

Energy Investment Phase:

🕸Glucose is phosphorylated to glucose-6-phosphate by hexokinase.

🕸This reaction is dependent on ATP and Mg2+.

🕸Glucose-6-phosphate prevents the exit of glucose from the cell and primes it for further metabolic pathways.

🕸Fructose-6-phosphate is phosphorylated to fructose-1,6-bisphosphate by Phosphofructokinase (PFK).

🕸This step is a key regulatory point in glycolysis, It commits glucose to glycolysis.

Splitting Phase:

🕸Fructose-1,6-bisphosphate is split into two three-carbon compounds: glyceraldehyde-3-phosphate (G3P) and dihydroxyacetone phosphate (DHAP).

🕸Catalyzed by fructose-1,6-bisphosphate aldolase.

🕸Triose phosphate isomerase converts DHAP into another molecule of G3P.

🕸This step ensures both molecules can proceed through glycolysis.

Energy Generation Phase:

🕸Glyceraldehyde-3-phosphate dehydrogenase catalyzes the conversion of G3P to 1,3-bisphosphoglycerate.

🕸NAD+ is reduced to NADH during this step, which stores energy in the form of reducing equivalents.

💫Phosphoglyceraldehyde Kinetes:

🕸These enzymes catalyze the conversion of 3-phosphoglycerate (3-PG) to 2-phosphoglycerate (2-PG), a crucial step in glycolysis.

🕸PGk1and PGK2 are isoforms of phosphoglycerate mutase, which convert 3-phosphoglycerate to 2-phosphoglycerate in the glycolytic pathway.

💫Endase Genecases:

🕸Likely referring to endase enzymes such as phosphoglycerate kinase, which catalyze the transfer of phosphate from 1,3-bisphosphoglycerate to ADP, forming ATP, a critical step in substrate-level phosphorylation.

💫Flusede Inhibition:

Possibly refers to fluoride, which inhibits enolase, a key enzyme in glycolysis, affecting glucose metabolism.

💫High Energy ADP:

Likely high-energy ADP, indicating ATP formed during glycolysis, a process vital for cellular energy production.

💫Conversion Of Pyruvate-Lactate–significances:

🕸 Possibly refers to lactate and its significance in anaerobic conditions, where pyruvate is reduced to lactate by lactate dehydrogenase, regenerating NAD+ for continued glycolysis in the absence of oxygen.

🕸These tissues rely on anaerobic glycolysis for energy, showcasing the importance of lactate production in maintaining energy supply.

Regulation of Glycolysis

🕸The three enzymes hexokinase, phosphofructokinase (PFK), and pyruvate kinase catalyze the necessary reactions regulating glycolysis.

1.Hexokinase:

☀This enzyme prevents the accumulation of fructose 6-phosphate by catalyzing its conversion to glucose 6-phosphate.

☀It is an inducible enzyme inhibited by glucose, ensuring the regulation of glucose influx.

2.Phosphofructokinase (PFK):

☀PFK is the key regulatory enzyme in glycolysis, catalyzing the rate-limiting step.

☀It is allosterically regulated by several molecules including ATP, citrate, and AMP. Among these, fructose 2,6-bisphosphate (F2,6BP) is a potent activator, promoting glycolytic flux.

3.Pyruvate Kinase:

☀Pyruvate kinase is inhibited by ATP and activated by fructose 1,6-bisphosphate (F1,6BP).

☀It exists in an active (dephosphorylated) state and an inactive (phosphorylated) state, regulated by phosphorylation via mechanisms like cAMP-dependent protein kinase.

☀In summary, hexokinase, PFK, and pyruvate kinase play crucial roles in regulating glycolysis, ensuring that glucose metabolism is finely tuned to meet cellular energy demands.