Ch 9 - Carbohydrate Metabolism I Flashcards
Where is GLUT2 found? Can it be saturated at normal glucose levels and is it responsive to insulin?
- in the liver for glucose storage
- in pancreatic beta-islet cells as part of the glucose sensor
- have a high Km
- cannot be saturated under normal physiological conditions
- not responsive to insulin
Where is GLUT4 found? Can it be saturated at normal glucose levels and is it responsive to insulin?
- in adipose tissue and muscle and is stimulated by insulin
- has a low Km
- saturated when glucose levels are only slightly above 5mM
Where does glycolysis occur and what does it produce?
- occurs in the cytoplasm of all cells and does not require oxygen
- yields 2 ATP per molecule of glucose
What is glucokinase role in glycolysis?
- phosphorylates and traps glucose in liver and pancreatic cells to form glucose 6-phosphate
- works with GLUT2, present in the pancreatic beta-islet cells as part of the glucose sensor and is responsive to insulin in the liver
- high Km (acts on glucose proportionally to its concentration)
- induced by insulin in hepatocytes
- irreversible
What is hexokinase role in glycolysis?
- phosphorylates glucose to form glucose 6-phosphate in peripheral tissues, trapping glucose in the cell
- low Km (reaches maximum velocity at low [glucose])
- inhibited by glucose-6-phosphate
- irreversible
What is phosphofructokinase-1 (PFK-1) role in glycolysis?
- rate limiting step of glycolysis (main control point)
- phosphorylates fructose 6-phosphate to fructose 1,6-bisphosphate using ATP
- activated by AMP and fructose 2,6-bisphosphate (F2,6-BP) and is inhibited by ATP, citrate, and glucagon
- irreversible
What is phosphofructokinase-2 (PFK-2) role in glycolysis?
produces the F2,6-BP that activates PFK-1
- activated by insulin and inhibited by glucagon
What is glyceraldehyde-3-phosphate dehydrogenase role in glycolysis?
produces NADH, which can feed into the electron transport chain, while phosphorylating 3-phosphate to 1,3-bisphosphate
- reversible
What is 3-phosphoglycerate kinase and pyruvate kinase roles in glycolysis?
- each perform substrate level phosphorylation, placing an inorganic phosphate onto ADP to form ATP
- 3: transfer phosphate from 1,3-diphosphoglycerate to ADP, forming ATP and 3-phosphoglycerate (reversible)
- pyruvate: transfer phosphate from PEP to ADP, forming ATP and pyruvate (irreversible)
Which enzymes catalyze irreversible reactions in glycolysis?
How Glycolysis Pushes Forward the Process: Kinases Hexokinase Glucokinase PFK-1 Pyruvate Kinase
What oxidizes the NADH produced in glycolysis?
- the mitochondrial electron transport chain when oxygen is present
- if oxygen or mitochondria is absent, oxidized by the cytoplasmic lactate dehydrogenase (ex. RBCs, skeletal muscle, any cell deprived of oxygen)
Where does galactose come from and what does it do?
- comes from lactose in milk
- trapped in cell by galactokinase, and converted to glucose 1-phosphate via galactose-1-phosphate uridyltransferase and an epimerase
Where does fructose come from and what does it do?
- comes from honey, fruit, and sucrose
- trapped in the cell by fructokinase, and then cleaved by aldolase B to form glyceraldehyde and DHAP
What is pyruvate dehydrogenase?
- a complex of enzymes that convert pyruvate to acetyl-CoA
- stimulated by insulin and inhibited by acetyl-CoA
What is glycogenesis?
the production of glycogen using 2 main enzymes: glycogen synthase and branching enzyme
What does glycogen synthase do in glycogenesis?
- rate limiting step for glycogenesis
- creates alpha-1,4 glycosidic links between glucose molecules
- activated by insulin in liver and muscle
What do branching enzymes do in glycogenesis?
moves a block of oligoglucose from one chain and adds it to the growing glycogen as a new branch using an alpha-1,6 glycosidic link
What is glycogenolysis?
the breakdown of glycogen using 2 main enzymes: glycogen phosphorylase and debranching enzymes
What does glycogen phosphorylase do in glycogenolysis? How is it activated in liver v skeletal muscle?
- rate limiting step for glycogenolysis
- removes single glucose 1-phosphate molecules by breaking alpha-1,4, glycosidic links
- in liver, it is activated by glucagon to prevent low blood sugar
- in exercising skeletal muscle, it is activated by epinephrine and AMP to provide glucose for the muscle itself
What do debranching enzymes do in glycogenolysis?
- moves a block of oligoglucose from one branch and connects it to the chain using an alpha-1,4, glycosidic link
- also removes the branchpoint, which is connected via an alpha-1,6, glycosidic link, releasing a free glucose molecule
What is gluconeogenesis and where does it occur?
- occurs in both cytoplasm and mitochondria, predominantly in the liver (small kidney contribution)
- most is simply the reverse of glycolysis, using the same enzymes
How does pyruvate carboxylase help in bypassing the irreversible steps of glycolysis in gluconeogenesis?
- pyruvate carboxylase converts pyruvate into oxaloacetate, which is converted to phosphoenolpyruvate by phosphoenolpyruvate carboxykinase (PEPCK)
- together, these enzymes bypass pyruvate kinase
- pyruvate carboxylase is activated by acetyl-CoA from beta oxidation; PEPCK is activated by glucagon and cortisol
How does fructose-1,6-bisphosphate help in bypassing the irreversible steps of glycolysis in gluconeogenesis?
- rate limiting step for gluconeogenesis
- converts fructose 1,6-bisphosphate to fructose-6-phosphate, bypassing phosphofructokinase-1
- this is the rate limiting step of gluconeogenesis
- activated by ATP directly and glucagon indirectly (via decreased levels of fructose-2,6-bisphosphate)
- inhibited by AMP directly and insulin indirectly (via increased levels of fructose-2,6-bisphosphate)