Glycolysis Overview and Phases

Overview

This lecture covers glycolysis, the first step of glucose breakdown for energy, describing its key phases, steps, and net yields of ATP and NADH.

Glycolysis is the anaerobic process that breaks down one glucose molecule into two pyruvate molecules.
The process occurs in the cytoplasm of both prokaryotic and eukaryotic cells.
Glycolysis does not require oxygen and is used by nearly all living organisms.
Glucose enters the cell via secondary active transport or facilitated diffusion through GLUT proteins.

Glycolysis has two phases: the energy investment phase and the energy payoff phase.
The first phase uses 2 ATP to split glucose into two 3-carbon molecules.
The second phase generates 4 ATP and 2 NADH, resulting in a net gain of 2 ATP.

Step 1: Hexokinase phosphorylates glucose using 1 ATP, forming glucose-6-phosphate.
Step 2: Phosphoglucose isomerase converts glucose-6-phosphate to fructose-6-phosphate.
Step 3: Phosphofructokinase phosphorylates fructose-6-phosphate using another ATP to create fructose-1,6-bisphosphate; acts as a rate-limiting enzyme.
Step 4: Aldolase splits fructose-1,6-bisphosphate into dihydroxyacetone phosphate and glyceraldehyde-3-phosphate.
Step 5: Isomerase converts dihydroxyacetone phosphate to glyceraldehyde-3-phosphate; two 3-carbon molecules proceed.

Step 6: Glyceraldehyde-3-phosphate is oxidized and phosphorylated, forming NADH and 1,3-bisphosphoglycerate.
Step 7: Phosphoglycerate kinase transfers a phosphate to ADP, forming ATP and 3-phosphoglycerate.
Step 8: Mutase converts 3-phosphoglycerate to 2-phosphoglycerate.
Step 9: Enolase dehydrates 2-phosphoglycerate, forming phosphoenolpyruvate (PEP).
Step 10: Pyruvate kinase transfers a phosphate from PEP to ADP, yielding another ATP and pyruvate.

For each glucose: 2 pyruvate, 2 net ATP (4 produced, 2 used), and 2 NADH are formed.
Glycolysis is the sole ATP source for cells lacking mitochondria (e.g., mature red blood cells).
The pathway depends on enzymes like phosphofructokinase and pyruvate kinase, which are rate-limiting.

Glycolysis — The metabolic pathway that breaks down glucose into pyruvate, yielding ATP and NADH.
GLUT proteins — Transporters that mediate facilitated diffusion of glucose into cells.
Hexokinase — Enzyme that phosphorylates glucose in the first glycolysis step.
Phosphofructokinase — Key enzyme controlling glycolysis rate via ATP/ADP levels.
NAD+ / NADH — Electron carrier; NAD+ accepts electrons, forming NADH during oxidation.
Substrate-level phosphorylation — ATP production by direct transfer of phosphate to ADP.