Glycolysis Flashcards
Glycolysis
Metabolic pathway converting glucose to pyruvate
Where does glycolysis occur?
Cytoplasm
Where is Glycolysis Used?
Used in all cells where glucose is broken down to provide ATP and intermediated for other pathways
Phases of GLycolysis
Stage 1: Energy Investment Phase (first 5 rxns)
Stage 2: Energy generation phase
(final 5 rxns)
Energy Investment Phase
- Step 1 and 3 are regulatory steps; reguire ATP
- 1 glucose has been oxidized to two G3P
- 2 ATP are consumes
Energy Generation Phase
- start w/ two molecules of G3P
- Generate 2 NADH, 4ATP, 2 pyruvate
- pyruvate and NADH can be further ox. in TCA and ETC respectively (produce more ATP)
What happens to pyruvate under aerobic conditions?
- Pyruvate is converted to Acetyl-CoA and enters further oxidation
- NADH is oxidized via ETC
- In order for glycolysis to continue must oxidize NADH to resupply NAD+ (NAD+ is limited in cell)
Fates of Pyruvate
- acetaldehyde
- lactate
- Acetyl CoA
Anaerobic Glycolysis
- when there is a lack of O2 cells use lactic acid fermentation to regenerate NAD+
Aerobic glycolysis yield
Gain 2 ATP/glucose
- ongoing glycolysis req. ox. of NADH by ETC
Anaerobic glycolysis yield
Gain 2 ATP/glucose
- no net production or consumption of NADH
3 key regulatory rxns of glycolysis
- Hexokinase; catalyzes 1st rxn
- Phosphofructokinase; catalyzes 3rd rxn
- Pyruvate Kinase; catalyzes last rxn
PFK-1
- P from ATP transferred to fructose 6-P by PFK to form fructose 1,6-bisphosphate
- commited step
Hexokinase
- P from ATP is added to glucose to form glucose 6-phosphate
- catalyzed by hexokinase or glucokinase (liver)
- traps glucose in cell
- product inhibition; Hex. inhibited by G-6P
Pyruvate Kinase
- transfers P from PEP to ADP
- forms ATP and pyruvate
- all three rxns are irreversible steps
Glycolysis plays 2 roles
1-degrades glucose to generate ATP
2-provides building blocks for biosynthetic rxns
How is glycolysis regulated?
- by 3 regulatory enzymes
- by reversible binding of allosteric effectors and/or covalent modifications
Regulation of glycolysis in muscle w/ PFK
- ratio of ATP/AMP indicates energy level of cell
- PFK; the most important regulatory point for glycolysis
- inhibited by high levels of ATP
- activated by AMP
Primary role of glycolysis in muscle?
Provide ATP
Regulation of glycolysis in muscle w/ Hexokinase
- phosphorylates glucose in first step
- inhibited by product - G-6P
- G-6P also increases when PFK is inhibited, PFK inhibited - hexokinase inhibition
Regulation of glycolysis in muscle w/ Pyruvate kinase
- catalyzes final step of glycolysis
- allosterically inhibited by ATP
- activated by Fructose 1,6-bisphosphate (product of PFK)
Regulation of glycolysis in liver
- Liver is amore biochemically diverse tissue
- Liver maintains blood glucose conc.
- more complex tissue leads to more complex reg.
How does liver maintain bloodglucose conc.
- stores glucose as glycogen
- synthesizes new glucose via gluconeogenesis
- uses glucose to make building blocks for other molecules
Regulation of glycolysis in liver w/ PFK
Regulated by ATP, similar to liver
- less ATP, therefore less sig. regulation
- liver also produces C skeletons for biosynthesis, thus availability of these molecules regulates PFK
- Citrate; inhibit
- high levels of citrate indicate high levels of biosynthetic precursors
- elevated blood glucose signalled by fructose 2,6-bisphosphate conc.
Regulation of glycolysis in liver w/ Hexokinase
- Hexokinase/Glucokinase are isozymes
- isozymes; enzymes encoded by diff. genes that catalyze the same rxn
Glucokinase
- Primary enzyme for phosphorylation of glucose in the liver
- Also found in pancreatic cells where glucose 6-P stimulates release of insulin
When does glucokinase phosphorylate gluicose
- when glucose levels are high
Regulation of glycolysis in liver w/ Pyruvate kinase
- pyruvate kinase; muscle and liver cells have diff. isozymes
- both respond to allosteric regulation
- inhibited by ATP
- Activated by Fructose 1,6-BP
What is liver isozyme also regulated by?
- By phosphorylation
- triggered by glucagon
What is PFK-1 in muscles inhibited by?
ATP
What is hexokinase in muscles activated by?
Substrate
What is PFK-1 in muscles activated by?
AMP
What is hexokinase in muscles inhibited by?
G-6P
What is pyruvate kinase in muscles activated by?
Fructose 1,6-bisphosphate
What is pyruvate kinase in muscles inhibited by?
ATP
What is hexokinase/glucokinase in liver inhibited by?
G-6P
What is hexokinase/glucokinase in liver activated by?
Glucose
What is PFK-1 in liver activated by?
- Fructose 2,6-BP
-AMP
What is PFK-1 in liver inhibited by?
- ATP
- Citrate
What is pyruvate kinase in liver activated by?
- Fructose 1,6-BP
- Dephosphorylation
What is pyruvatekinase in liver inhibited by?
- ATP
- Phosphorylation
