Glycolysis

Glycolysis Overview

  • Definition: Glycolysis is the process of oxidizing glucose, a six carbon molecule (monosaccharide), into pyruvate (two three carbon molecules).

  • Glucose is obtained from the diet, particularly from carbohydrates.

Glucose and Cell Membrane Transport

  • Glucose is a water-soluble solute, thus it cannot diffuse through the cell membrane and requires a transporter.

  • Transporters: Specialized transporters are known as GLUT (glucose transporters).

    • They are bidirectional, allowing glucose to enter or exit the cell.

Types of GLUT Transporters

  • Mnemonic for GLUT Transporters: "BBB, KI, PS, P, k"

    • GLUT 1:

    • B: Blood (red blood cells)

    • B: (Fetus) conveys the distribution of GLUT in fetal tissues.

    • B: Blood-brain barrier (separation between blood vessels and neural tissue).

    • GLUT 2:

    • K: Kidneys

    • L: Liver

    • P: Pancreas.

    • GLUT 3:

    • P: Placenta

    • N: Neurons

    • K: Kidneys

    • GLUT 4:

    • M: Muscle

    • F: Adipose (fat) tissue.

Special Characteristics of GLUT Transporters

  • GLUT 4 is insulin-dependent, meaning insulin increases its effectiveness or number, unlike GLUT 1, 2, and 3, which are insulin-independent.

The Glycolysis Steps

Step 1: Phosphorylation of Glucose

  • Entry of Glucose: Once glucose enters the cell through the appropriate GLUT transporter, it undergoes phosphorylation.

  • Phosphorylation Process: A phosphate group is added to glucose (on the sixth carbon), forming Glucose-6-Phosphate (G6P).

    • This process requires an enzyme: Hexokinase (found in many tissues, predominantly muscle) or Glucokinase (found in the liver).

    • ATP to ADP Conversion: ATP donates a phosphate group, converting to ADP.

Step 2: Isomerization

  • Conversion of G6P to Fructose-6-Phosphate (F6P):

    • Enzyme: Phosphohexose Isomerase.

    • Isomerization occurs between the aldehyde (glucose) and ketone (fructose) forms.

Step 3: Second Phosphorylation (Irreversible Step)

  • Conversion of F6P to Fructose-1,6-Bisphosphate (F1,6BP):

    • Enzyme: Phosphofructokinase-1 (PFK-1).

    • ATP is utilized, and one phosphate is added at the first carbon.

Step 4: Cleavage

  • F1,6BP splits into Dihydroxyacetone Phosphate (DHAP) and Glyceraldehyde-3-Phosphate (GAP):

    • Enzyme: Aldolase.

    • DHAP must be converted into GAP (a reversible process).

Step 5: Isomerization of DHAP

  • Interconversion of DHAP and GAP:

    • Enzyme: Triose Phosphate Isomerase.

Step 6: Oxidation and Phosphorylation of GAP

  • GAP to 1,3-Bisphosphoglycerate (1,3BPG):

    • Enzyme: Glyceraldehyde-3-Phosphate Dehydrogenase (GAPDH).

    • NAD extsuperscript{+} is reduced to NADH, and an inorganic phosphate is added.

Step 7: ATP Production

  • Conversion of 1,3BPG to 3-Phosphoglycerate (3PG):

    • Enzyme: Phosphoglycerate Kinase.

    • ATP is produced through substrate-level phosphorylation (2 ATP formed from 2 reactions).

Step 8: Mutate the Phosphate

  • 3PG to 2-Phosphoglycerate (2PG):

    • Enzyme: Phosphoglycerate Mutase.

Step 9: Dehydration to form an Enol

  • Conversion of 2PG to Phosphoenolpyruvate (PEP):

    • Enzyme: Enolase.

    • An intermediate enol is formed with a double bond and phosphate.

Step 10: Final Conversion to Pyruvate

  • PEP to Pyruvate:

    • Enzyme: Pyruvate Kinase.

    • ATP is produced again through substrate-level phosphorylation (2 ATP formed from 2 reactions).

Summary of Glycolysis Products

  • Location: Cytoplasm of the cell.

  • Starting Substrate: Glucose.

  • End Product: 2 Pyruvate molecules.

  • ATP Production: Gross of 4 ATP; Net gain of 2 ATP after accounting for initial investment of 2 ATP.

  • NADH Production: 2 NADH generated.

  • Anaerobic Conditions: In the absence of oxygen, pyruvate is converted into lactic acid via lactate dehydrogenase, resulting in metabolic acidosis due to lactic acid increase.

  • Clinical Significance: Elevated lactate dehydrogenase levels indicate pyruvate conversion to lactic acid under anaerobic conditions. This response occurs during myocardial infarction, necrotic tissue, and ischemia.

Future Topics

  • Transition Reaction: The fate of pyruvate under aerobic conditions leads to its conversion into acetyl-CoA in the next metabolic pathway.