Glycolysis Flashcards
What does glycolysis break down and produce?
Breaks down glucose and fructose to pyruvate
What happens to glycolysis when lacking oxygen, like ischemia?
Glycolysis persists because it does not require oxygen
Along with pyruvate, what does glycolysis produce per glucose?
2 ATP and 2NADH
What are the four steps in glycolysis?
- Hexokinase/Glucokinase
- Phosphofructokinase I
- GAPDH; PGK
- Pyruvate kinase
What is glycolysis most important for? Why?
Red blood cells - no mitochondria
Brain - can’t use fatty acids
Anaerobic environments - exercising muscles
What are other energy pathways besides glycolysis?
Mitochondrial fatty acid oxidation
Amino acid catabolism
Where does glycolysis occur?
Cytosol
What will a patient with a glycolytic disorder present with? Why?
- Hemolytic anemia - lysis of red blood cells
- Jaundice - degradation of hemoglobin released from red blood cells
- Enlarged spleen - removal of damaged RBCs
- Rare congenital disorders - pyruvate kinase deficiency
Why? Red blood cells rely exclusively on glycolysis
What steps of glycolysis require energy to be put in?
Hexokinase/Glucokinase converting glucose to glucose-6-phosphate
Phosphofructokinase I converting fructose 6-phosphate to fructose 1,6-bisphosphate
What steps of glycolysis create energy?
GAPDH converting glyceraldehyde 3P to 2 bisphosphoglycerate
2 bisphosphoglycerate being converted to 2 phosphoenolpyruvate by PGK
2 phosphoenolpyruvate to 2 pyruvate by pyruvate kinase
What regulates glycolysis?
Glucose availability and energy demand
When is glycolysis most active?
Glucose conc in blood high - high insulin/glucagon ration
Low energy - low ATP/AMP ratio
Unsaturated mitochondria - low citrate
What are the key regulatory points of glycolysis and why?
Hexokinase - entry of glucose
Phosphofructokinase I - committed step
Pyruvate kinase - exit point, entry to mitochondria
What is the main regulated step of glycolysis? What regulates it? x3
Phosphofructokinase I
3 main signals:
1. citrate - mitochondrial overload, repressor
- Insulin and glucagon - nutritional state via cAMP and F2,6BP
- ATP and AMP - energy state, repressed by high ATP
What signal integration goes through fructose 2,6 - bisphosphate?
Signals: insulin, glucagon, AMP, fructose 6P
No other function than to stimulate glucose catabolism
High F2,6 BP means high glucose catabolism
What step in glycolysis is often upregulated in cancer?
PFK II because it produces fructose 2,6 bisphosphate which stimulates glucose catabolism
How does cAMP regulate carbohydrate metabolism?
Glucagon - low blood glucose - signals cAMP
cAMP activates PKA to produce glucose by reducing glucose consumption and increasing glucose production
Glucose consumption
Increased glycolysis and increased glucose storage
Glucose production
Increased gluconeogenesis and increased mobilization of glucose from storage
What is a hallmark of starvation? How does this relate to insulin?
Phophorylation of metabolic enzymes to boost blood glucose
Insulin dephosphorylates to indicated well-fed state
How does PGK and pyruvate kinase produce ATP?
Substrate level phosphorylation
What does glyceraldehyde 3P dehydrogenase produce? What happens to that product?
NADH! Oxidized to NAD to continue glycolysis
What activates and inhibits pyruvate kinase?
Activated by insulin and fructose 1,6-bisphosphate
Inhibited by ATP
What are inherited errors of metabolism and what do they involve?
IEM are mutations in the genes that code for enzymes for glycolytic degradation. These enzymes are required by galactose and fructose.
Disorders are present at birth and manifest upon ingestion of substance
Impeded development and can cause disability
How does fructose degradation differ between muscles and the liver?
Fructose in muscle –> Hexokinase yields F6P and is slow. Goes through normal glycolysis
Fructose in liver is degraded fast by fructokinase to yield F1P. Aldolase B is then required to cleave F1P so it can enter glycolysis
How does fructose metabolism work in relation to insulin?
Fructose metabolism occurs in the liver and does not trigger insulin release. Not dependent on insulin. Blood fructose does not signal fed state
Fructokinase deficiency, no accumulation of fructose in cells and fructose is excreted in urine, benign.
Essential fructosuria
Hereditary Fructose Intolerance. What occurs? How to treat?
Aldolase B deficiency
Fructose-P accumulation in liver, which depletes liver phosphate pools and impairs glycogen mobilization - leads to hypoglycemia
Liver damage - accumulation of glycogen, lack of Pi –> jaundice
Treat by avoiding fructose and sucrose
What enzymes degrade galactose to glucose?
Galactokinase
Galactose uridyltransferase
Epimerase
What has to happen to galactose to become glucose?
Has to become a UDP-bound galactose
Galactosemia. What are the possible causes? What do patients present with?
Galactose-1-phosphate uridyl transferase deficency – galactose P accumulates
UDP-galactose epimerase deficiency
Galactokinase deficiency
Newborns present with milk intolerance and sign of liver failure (jaundice)
What happens to NADH during and after glycolysis?
Re-oxidized to NAD during glycolysis
Lactase dehydrogenase produce lactate with oxidation of NADH
Lactate oxidized back to pyruvate, liver converts lactate to glucose, brain can use lactate for energy
NADH can be used to shuttle electrons into mitochondria
Cori Cycle
Lactate taken up by liver and converted to pyruvate
Pyruvate converted back to glucose
Mitochondrial Shuttles
Glycerol phosphate shuttle - muscle and brain, oxidize NADH, reduce FAD –> FADH
Malate/Aspartate shuttle - liver and heart, efficient, oxidize NADH and then reduce NAD to –> mitosolic NADH
