Glycolysis Flashcards
What are the four glucose transporters?
- GLUT1
- GLUT2
- GLUT3
- GLUT4
GLUT2
- low-affinity transported in hepatocytes (liver cells) and pancreatic cells (specifically on the beta-islet cells)
- capture excess glucose for storage
- high Km
- can’t be saturated under normal physiological conditions
- not responsive to insulin but serves as glucose sensor to cause release of insulin in pancreatic beta-cells
GLUT4
- present in adipose and muscle tissue
- Km is low and close to normal glucose levels in blood so the transporter is saturated when blood glucose levels are slightly elevated compared to normal
- transport rate increases when insulin level increases
What is the role glucose plays in adipose tissue?
glucose is required to form DHAP which is converted to glycerol phosphate to store incoming fatty acids as triacylglycerols
Glycolysis
- carried out by all cells in their cytoplasm
- the only energy-yielding pathway for red blood cells
- does not require presence of oxygen
- converts glucose molecule into 2 pyruvate molecules, releasing energy captured in two substrate-level phosphorylations and one oxidation reaction
- 2 NADH from glycolysis typically leads to 3 ATP, giving this process a total of 5 ATP produced
What monosaccharides can enter glycolysis pathway?
- glucose
- galactose
- fructose
List the enzymes used in glycolysis in order (10)
- Hexokinase (or if in liver/pancreas then Glucokinase)
- Phosphoglucose Isomerase
- Phosphofructose Kinase
- Fructose Bisphosphate Aldose
(5. Triose Phosphate Isomerase) - Glyceraldehyde 3-Phosphate Dehydrogenase
- Phosphoglycerate Kinase
- Phosphoglycerate Mutase
- Enolase
- Pyruvate Kinase
Which enzymes are irreversible?
- How Glycolysis Pushes Forward the Process: Kinases*
- Hexokinase
- Glucokinase
- PFK-1
- Pyruvate Kinase
Hexokinase
- phosphorylates glucose to form glucose 6-phosphate
- requires ATP input
- “traps” glucose in cell
- inhibitor: glucose 6-phosphate
- activator: AMP/ADP
- irreversible
- low Km [reaches max velocity at low concentrations of glucose]
Glucokinase
- phosphorylates glucose to form glucose 6-phosphate
- requires ATP input
- “traps” glucose in cell
- only found in liver cells and pancreatic beta-islet cells
- irreversible
- high Km [low affinity for glucose so requires high concentrations of glucose to achieve Vmax]
- responsive to insulin in liver
- induced by insulin
Phosphofructokinase-1 (PFK-1)
- allosteric enzyme that regulates the pace of glycolysis
- rate-limiting enzyme
- phosphorylates fructose 6-phosphate to fructose 1,6-bisphosphate
- requires ATP input
- irreversible
- inhibitors: ATP, citrate, glucagon
- activators: AMP, fructose 2,6-bisphosphate, insulin
Phosphofructokinase-2 (PFK-2)
- produces the fructose 2,6-bisphosphate that activates PFK-1
- mostly found in liver
- allows cells to over-ride inhibition caused by ATP so glycolysis can continue
- inhibitors: glucagon
- activators: insulin `
Glyceraldehyde-3-Phosphate Dehydrogenase
- dehydrogenates glyceraldehyde 3-phosphate to 1,3-bisphosphoglycerate
- during this reaction, NAD+ is reduced to NADH (oxidation) which is coupled to the phosphorylation of the substrate to form the 1,3-bisphosphoglycerate product
- reversible rxn
3-Phosphoglycerate Kinase
- substrate level phosphorylation – transfers phosphate group from 1,3-bisphosphoglycerate to ADP, forming ATP and 3-phosphoglycerate
- step produces 2 ATP/ glucose
- reversible rxn that does not depend on oxygen so is only source of ATP in ANAEROBIC tissue
Pyruvate Kinase
- final enzyme in AEROBIC glycolysis
- catalyzes substrate-level phosphorylation of ADP using substrate phosphoenolpyruvate (PEP)
- activated by fructose 1,6 bisphosphate from PFK-1 rxn (this is example of feed-forward activation because product of earlier reaction stimulates a later rxn)
- activators: fructose 1,6 bisphosphate, AMP/ADP
- inhibitors: ATP, acetyl-CoA, Alanine
Glycolysis Net Reaction:
Glucose + 2 NAD+ + 2 Pi + 2 ADP = 2 pyruvate + 2 ATP + 2 NADH + 2 H2O
What happens to pyruvate in the presence of O2?
it is further oxidized to CO2
What happens to pyruvate in the absence of O2?
it can be fermented to lactate or ethanol
Fermentation
- occurs after glycolysis when oxygen is absent (anaerobic conditions)
- occurs in cytoplasm of cell
- prevents glycolysis from stopping by reducing pyruvate to lactate and oxidizing NADH to NAD+ via lactate dehydrogenase
- key enzyme: lactate dehydrogenase
Lactate Dehydrogenase
- important enzyme in fermentation
- oxidizes NADH to NAD+, replenishing the oxidized coenzyme for glyceraldehyde-3-phosphate dehydrogenase
What is the only pathway for ATP production in erythrocytes (RBCs)?
anaerobic glycolysis – yields a net 2 ATP / glucose
Bisphosphoglycerate Mutase
- enzyme present in RBCs-
- produces 2,3-bisphosphoglycerate from glycolysis molecule 1,3-bisphosphoglycerate
Explain the relationship between 2,3-Bisphosphoglycerate (2,3-BPG) and Hemoglobin
- 2,3-BPG binds allosterically to the beta chains of Hemoglobin A and decreases its affinity for oxygen
- leads to a rightward shift (Bohr Shift) in Hb dissociation curve, making O2 unloading at tissues easier while still allowing 100% saturation in lungs
What conditions shift Hb dissociation curve right?
- increased CO2
- increased H+ concentration (same as decreased pH)
- increased temperature
- increase in 2,3-BPG
What does a leftward shift in the Hb curve signify?
- increased Hb affinity for O2
- decreased O2 unloading at tissues
What conditions shift Hb dissociation curve left?
- decreased CO2
- decreased H+ concentration (same as increased pH)
- decreased temperature
- decrease in 2-3-BPG
Fetal Hemoglobin (HbF)
- has increased affinity for O2 which allows for transplacental passage of O2 from mother to infant
- causes a leftward shift in Hb dissociation curve
- 2,3-BPG does not bind well to HbF
Pyruvate Dehydrogenase Complex
- complex that pyruvate products from glycolysis enter under aerobic conditions
- irreversible
- in the liver it is activated by insulin
- converts pyruvate to acetyl Co-A via enzyme pyruvate dehydrogenase (PDH), which also produces NADH and CO2
- complex requires: thiamine pyrophosphate, lipoic acid, CoA, FAD, NAD+
- inhibitors: acetyl CoA
What are the two enzymes that regulate PDC?
- Pyruvate Dehydrogenase Kinase
- Pyruvate Dehydrogenase Phosphatase
Pyruvate Dehydrogenase Kinase
- enzyme that phosphorylates PDH thus inhibiting acetyl-CoA production from pyruvate
- activators: ATP, acetyl-CoA, NADH
Pyruvate Dehydrogenase Phosphatase
- enzyme that removes a phosphate from PDH which activates acetyl-CoA production from pyruvate
- activators: ADP, NAD+, pyruvate
What are the products of PDC (from one glucose)?
2 CO2 and 2 NADH
How many ATP could be produced from PDC (from one glucose)?
5 ATP
What are the 3 possible fates of pyruvate?
- conversion to acetyl CoA by pyruvate dehydrogenase
- conversion to lactate by lactate dehydrogenase (fermentation)
- conversion to oxaloacetate by pyruvate carboxylase (gluconeogenesis)
