Glycolysis - Investment Phase
- Citric Acid Cycle (TCA, Krebs)
- Glycolysis - Investment Phase
- Glycolysis - Payoff Phase
- Pentose Phosphate Pathway - Oxidative Phase
- Pentose Phosphate Pathway - Non-Oxidative Phase
- Glycogenesis
- Glycogenolysis
- Gluconeogenesis
- Electron Transport Chain (ETC)
Summary
Glycolysis is a metabolic pathway that breaks down sugar molecules to produce high energy molecules, like ATP and NADH. It can be broken into two phases: an investment phase and a payout phase.
In the investment phase, energy is ‘invested’ in the form of ATP. In the first step, hexokinase catalyzes the transfer of a phosphate group from ATP to glucose. This step is an important point of regulation, as it’s an irreversible step that traps glucose in the cell.
Next, glucose-6-phosphate is isomerized to fructose-6-phosphate via phosphoglucoisomerase.
Next, PFK -- or phosphofructokinase -- catalyzes the transfer of another phosphate group from ATP molecule to produce fructose-1,6-bisphosphate. This step is irreversible and is often the most important point of regulation.
Aldolase next splits fructose-1,6-bisphosphate into G3P and DHAP. G3P and DHAP are isomers that are interconverted by Triosephosphate Isomerase (TPI) because only G3P can proceed to the payout phase of Glycolysis.
Key Points
- Glycolysis Investment Phase
- Etymology
- Glyco- = glucose = sugar
- -lysis = to cut/split
- Summary
- Glycolysis is a metabolic pathway breaks down glucose to produce energy
- Other carbohydrates are metabolized by the pathway as well
- Occurs in the cytosol of the cell
- part of anaerobic respiration
- Can function with or without the presence of oxygen
- Ancient pathway
- highly conserved across different forms of life
- Present in aerobic and anaerobic organisms
- part of anaerobic respiration
- two phases
- Investment phase
- 2 ATP are ‘invested’ into glucose metabolism
- Payoff phase
- 4 ATP and 2 NADH are produced
- Net payoff: 2 ATP and 2 NADH (per glucose)
- Investment phase
- Glycolysis is a metabolic pathway breaks down glucose to produce energy
- reaction steps (investment phase)
- Glucose → [hexokinase] Glucose-6-phosphate
- Kinases catalyze the transfer of a phosphate group
- a phosphate group is transferred from ATP to Glucose
- Phosphate transferred to #6 carbon in glucose
- a phosphate group is transferred from ATP to Glucose
- Commits glucose to the pathway
- Glucose-6-phosphate cannot diffuse out of the cell
- powered by 1 ATP
- Irreversible (regulatory site)
- Kinases catalyze the transfer of a phosphate group
- Glucose-6-phosphate → [Phosphoglucoisomerase] fructose-6-phosphate
- Isomerases catalyze conversions between isomers
- Glucose-6-phosphate and fructose-6-phosphate are isomers
- Isomerases catalyze conversions between isomers
- Fructose-6-phosphate [phosphofructokinase (PFK)] → Fructose-1,6-bisphosphate
- Kinases catalyze the transfer of a phosphate group
- a phosphate group is transferred from ATP to fructose-6-phosphate (F6P)
- Phosphate transferred to #1 carbon in F6P
- a phosphate group is transferred from ATP to fructose-6-phosphate (F6P)
- powered by 1 ATP
- Irreversible rate-limiting step (main regulatory site)
- PFK reaction is the first irreversible step in this pathway that is unique to glycolysis
- Glucose-6-phosphate can be converted into glycogen or fed into the pentose phosphate pathway
- PFK reaction is the first irreversible step in this pathway that is unique to glycolysis
- Kinases catalyze the transfer of a phosphate group
- Fructose-1,6-bisphosphate → [Aldolase] dihydroxyacetone phosphate (DHAP) + glyceraldehyde-3-phosphate (G3P)
- Triosephosphate isomerase (TPI) catalyzes the interconversion between DHAP and G3P
- Only G3P proceeds to the payoff phase
- As G3P gets converted to the next intermediate, it decreases in concentration
- This ‘pulls’ more DHAP to convert to G3P based on Le Chatlier’s principle
- Eventually all DHAP will either be converted to G3P to enter the payoff phase
- For every 1 molecule of glucose, 2 molecules of G3P enter payoff phase
- Only G3P proceeds to the payoff phase
- Triosephosphate isomerase (TPI) catalyzes the interconversion between DHAP and G3P
- Glucose → [hexokinase] Glucose-6-phosphate
- Regulation
- Regulation is based on energy need and blood glucose levels
- Glycolysis speeds up when cells need to produce more energy and slows down when they don’t
- Glycolysis speeds up when blood glucose levels are high and slows down when they are low
- Regulatory steps
- PFK reaction is the primary regulatory step
- Regulation at other reversible steps as well
- PFK reaction is the primary regulatory step
- Glycolysis speeds up (activation)
- High energy need
- AMP
- High blood glucose levels
- Insulin
- Insulin activates PFK-2, increasing Fructose-2,6-bisphosphate (F26BP) levels
- Fructose-6-phosphate → [phosphofructokinase-2 (PFK-2)] Fructose-2,6-bisphosphate
- F26BP activates PFK
- Allows liver cells to override ATP inhibition
- Insulin activates Glucokinase
- Glucokinase is an alternative catalyst to hexokinase for the first reaction of glycolysis
- Glucokinase is only found in the liver and in the pancreas.
- Insulin activates PFK-2, increasing Fructose-2,6-bisphosphate (F26BP) levels
- Insulin
- High energy need
- Glycolysis slows down (inhibition)
- Low energy need
- ATP
- Citrate
- Citrate is a TCA intermediate, so high Citrate levels mean higher levels of energy production
- Glucose-6-phosphate
- Feedback inhibition on hexokinase
- Glucose-6-phosphate builds up when the pathway is regulated at a later step
- Feedback inhibition on hexokinase
- Low blood glucose levels
- Glucagon
- Inhibits PFK-2, decreasing Fructose-2,6-bisphosphate (F26BP) levels
- Glucagon
- Low energy need
- Regulation is based on energy need and blood glucose levels
- Etymology