Glycolysis: The process of oxidizing glucose, a six-carbon monosaccharide (sugar), into pyruvate, which consists of two three-carbon molecules.
Entry of Glucose into Cells
Glucose is a water-soluble solute and cannot diffuse through cell membranes.
Requires specialized transporters called GLUT (Glucose Transporters).
GLUT Transporters: Bidirectional, allowing glucose to enter or exit cells.
Types of GLUT Transporters
GLUT1:
Found in red blood cells and the fetal tissues.
Also in the blood-brain barrier (BBB).
GLUT2:
Found in the kidney, liver, and pancreas.
Present in the gastrointestinal tract.
GLUT3:
Found in neurons and placenta.
GLUT4:
Present in muscle and adipose (fat) tissue.
Insulin-dependent: Affected by insulin levels, increases the number or efficiency of GLUT4 transporters.
Phosphorylation of Glucose
Glucose enters the cell via GLUT transporters.
First Step: Phosphorylation of glucose to form Glucose-6-Phosphate (G6P).
Enzymes involved:
Hexokinase: Present in many tissues, especially muscles.
Glucokinase: Primarily in the liver.
Phosphate Source: ATP is converted to ADP, providing the phosphate group.
Isomerization
Second Step: Conversion of G6P to Fructose-6-Phosphate (F6P).
Catalyzed by Phosphohexose Isomerase.
Regulatory Steps in Glycolysis
Third Step: Conversion of F6P to Fructose-1,6-Bisphosphate (F1,6BP).
Catalyzed by Phosphofructokinase-1 (PFK-1).
Irreversible step, highly regulated.
Requires ATP, which donates a phosphate.
Cleavage of Fructose
Fourth Step: Cleavage of F1,6BP into two three-carbon molecules:
Dihydroxyacetone Phosphate (DHAP)
Glyceraldehyde-3-Phosphate (G3P)
Enzyme: Aldolase.
Interconversion of Three-Carbon Molecules
Fifth Step: Isomerization between DHAP and G3P.
Enzyme: Triose Phosphate Isomerase.
Further Processing of G3P
Sixth Step: Conversion of G3P to 1,3-Bisphosphoglycerate (1,3BPG).
Enzyme: Glyceraldehyde-3-Phosphate Dehydrogenase.
NAD+ is reduced to NADH in this step.
Formation of ATP
Seventh Step: Conversion of 1,3BPG to 3-Phosphoglycerate (3PG).
Enzyme: Phosphoglycerate Kinase.
Produces ATP from ADP.
Mutase Reaction
Eighth Step: Conversion of 3PG to 2-Phosphoglycerate (2PG).
Enzyme: Phosphoglycerate Mutase.
Dehydration to Phosphoenolpyruvate
Ninth Step: Conversion of 2PG to Phosphoenolpyruvate (PEP).
Enzyme: Enolase.
Final Step
Tenth Step: Conversion of PEP to Pyruvate.
Enzyme: Pyruvate Kinase.
Produces additional ATP.
Byproducts of Glycolysis
Net Gain: 2 ATP (4 produced, 2 used), 2 NADH, and 2 pyruvate molecules.
Anaerobic Conditions
In the absence of oxygen, pyruvate is converted into lactic acid by lactate dehydrogenase, which also regenerates NAD+ from NADH.
Lactic acid can travel to the liver, where it may be converted back to glucose or used for ATP production.
Clinical Relevance
Elevated lactate dehydrogenase (LDH) levels can indicate conditions like myocardial infarction or necrosis due to lack of oxygen, leading to lactic acid accumulation.
Summary of Glycolysis
Location: Cytoplasm
Starting Substrate: Glucose
End Product: 2 Pyruvate
Net Gain: 2 ATP, 2 NADH
Anaerobic Process leading to Lactic Acid Formation.