Glycolysis & Gluconeogenesis Flashcards
Glycolysis def
Breakdown of Glucose to 2 Pyruvate
Function of glycolysis
Produce energy in the form form of ATP
NADH in the cytoplasm is worth how many ATP
2
NADH in the mitochondria is worth how many ATP
3
Where does glycolysis occur?
Common in Prokaryotic and Eukaryotic Cells:
1) Occurs in cytosol of cytoplasm
- anaerobic conditions->fermentation producing lactic acid or ethanol
- aerobic conditions-> aerobic respiration in mitochondria (Krebs cycle)
2) ALL TISSUE
Net Production of ATP in Glycolysis
6 ATP
Hexokinase
Glycolysis
Glucose-> Glucose 6 Phosphate
-Phosphoryl transfer at the expense of ATP
-phosphorylation of glucose traps inside cell, because there aren’t any transporters that can transport phosphorylate glucose
-cofactor- Divalent Cation (Mg2+ or Mn2+)
-Exergonic
-Irreversible Rxn
Regulation:
Allosteric regulated by: Glucose 6-Phosphate inhibits(feedback inhibition)
Hormonal Regulation:
Stimulated in the fed state by hormone insulin
Inhibited in the fasting state by hormone glucagon
Broad Substrate Specificity-phosphorylates many hexoses
When Hexokinase binds to Glucose
causes conformation change (cleft closing) in hexokinase
- Active site around glucose becomes more nonpolar which favors donation of gamma phosphate
- Excludes water from active site, which prevents hydrolysis of gamma phosphate by H20
Example of Induced Fit
Substrate Induced Fit Cleft closing is a general feature of kinases
Hexokinase vs Glucokinase
Hexokinase:
Low Km=High Affinity for glucose
Km<0.1 mM which permits efficient metabolism of glucose
Glucokinase:
- AKA hexokinase D or type IV
- found in adult kidney and liver and senses glucose levels
- High Km=Low affinity for glucose, allowing brain and muscles to have first call on glucose
Phosphohexose Isomerase
Glycolysis
Or Phosphoglucose Isomerase
Glucose 6-Phosphate-> Fructose 6-Phosphate
1) Reaction Type: Isomerization- conversion of aldose C-1 to Ketose C-2
2) Helper Molecules: NONE
3) Exergonic
4) Reversible Reaction
5) No regulation
Phosphofructose Kinase-1
Glycolysis
Fructose 6-Phosphate-> Frucose 1,6-Bisphosphate
MOST IMPORTANT CONTROL POINT OF METABOLISM
1) Reaction Type: Phosphoryl Transfer At the expense of ATP
2) No helper molecules
3) Exergonic
4) Irreversible
REGULATED:
Allosteric: regulated by energy charge
-Stimulated by Fructose 2,6 Bisphosphate and AMP
-Inhibited by ATP, citrate, and H+
Phosphofructose Kinase-2 (PFK-2)
synthesis of Fructose 2,6 Bisphosphate which stimulates PFK1 in glycolysis and inactivates gluconeogenesis
Adenylate Kinase
ADP +ADP -> ATP + AMP
salvages ATP from two ADP molecules
-primary reason AMP represents “low energy” charge
Aldolase A
Glycolysis
Fructose 1,6-Bisphosphate-> DHAP and Glyceraldehyde 3-Phosphate
1) Reaction Type: Aldol Cleavage
2) Helper molecules: NONE
3) Exergonic
4) Reversible
5) NOT REGULATED
Triose Phosphate Isomerase
Glycolysis **
Dihyroxyacetone Phosphate Glyceraldehye 3-Phosphate
at equilibrium 96% exist in DHAP 4% GAP
1) Reaction Type: Isomerization
2) Helper Molecules: NONE
3) ENDERGONIC
4) Reversible
NOT REGULATED
Phosphoglyceraldehyde Dehdyrogenase
Glycolysis
OR Glyceraldehyde 3-Phosphate Dehydrogenase
Glyceraldehyde 3-Phosphate-> 1,3-Bisphosphoglycerate
1) Reaction type: Phosphorylation coupled to oxidation of aldehyde to carboxylic acid at the expense of NAD+ 2) Helper molecule-coenzyme-NAD+ 3)Exergonic 4) Reversible 5) NOT REGULATED
3-Bisphosphoglycerate Kinase
Glycolysis **
OR Phosphoglycerate Kinase
1,3 Bisphosphoglycerate -> 3-Phosphoglycerate
1) Reaction Type: Transfer of Phosphoryl group from 1,3-BPG to ADP to regenerate ATP since 1,3-BPG has higher phosphoryl potential than ATP
* SUBSTRATE LEVEL PHOSPHORYLATION
2) Helper Molecules-NONE
3) ENDERGONIC
4) REVERSIBLE-unusal for kinases
5) NOT REGULATED
Phosphoglyceromutase
Glycolysis **
OR Phosphoglycerate Mutase
3-Phosphoglycerate-> 2-phosphoglycerate
1) Reaction type-Phosphoryl shift from C3 to C2
2) Helper Molecules-NONE
3) Endergonic
4) Reversible
5) NOT REGULATED
Enolase
Glycolysis
2-phosphoglycerate-> Phosphoenolpyruvate
1) Reaction type-dehydration
2) Helper molecules; NONE
3) Exergonic
4) reversible
5) NOT REGULATED
Pyruvate Kinase
Glycolysis (LAST STEP)
PEP-> Pyruvate
1) Reaction Type: Phosphoryl Transfer from PEP to ADP to regenerate to ATP since PEP has higher phosphorylation potential than ATP
2) Helper Molecules-NONE
3) Exergonic
4) Irreversible
REGULATED:
Allosterically regulated:
-Stimulated by Fructose 1,6-BP in feedforward stimulation
-Inhibited by ATP and Alanine
IN LIVER:
-inactivated by cAMP dependent Protein Kinase A; low blood glucose=increase glucagon which pyruvate kinase is phosphorylated and inactivated
Pyruvate Kinase Deficiency in RBCs
RBC lack mitochondria thus lack Pyruvate oxidation, Krebs cycle, and Electron Transport chain Thus depends on glycolysis for ATP production
PK deficiency causes change in shape of RBC due to insufficient energy production causing chronic hemolytic fever
3 fates of pyruvate post glycolysis
Fermentation:
- anaerobic conditions
- cytoplasm
1) Lactic acid-higher eukaryotes
2) ethanol-microorganisms
Pyruvate Oxidation
- aerobic conditions
- matrix of mitochondria
Pyruvate: Ethanol Fate
Fermentation-anerobic conditions
-occurs in cytoplasm
Pyruvate-> Acetaldehyde + CO2 -Enzyme: Pyruvate Decarboxylase Reaction type: decarboxylation -Helper Molecule: Prosthetic group-Thiamine pyrophosphate -Reversible -Exergonic
Acetaldehyde-> Ethanol Enzyme: Alcohol dehydrogenase Reaction type: oxidation Helper molecule- Zn2+-cofactor; NADH coenzyme exergonic REGENERATE NAD+
Pyruvate: Lactate Fate
Pyruvate-> Lactate
Enzyme: Lactate dehydrogenase
Lactate + Exercise
formation of lactate reduces pH potentially leading to cramps
-lactate diffuses into blood and can be used to make glucose in liver