Module 04 - Gluconeogenesis and Glycogen Metabolism (Section 04) Flashcards
Which 3 main sources is blood glucose obtained from?
- Diet
- Gluconeogenesis
- Glycogen Breakdown
What is Glucose Metabolism?
the net production of glucose (gluconeogenesis) and breakdown of glucose (glycolysis)
What is Gluconeogenesis?
an anabolic pathway that converts pyruvate (or lactate) to glucose
Where does Gluconeogenesis occur?
partially in the mitochondria and partically in the cytoplasm of liver and kidney cells
What are the 3 most important substrates for Gluconeogenesis?
- Glycerol from the breakdown of lipids
- Lactate released into the blood from red blood cells and exercising muscles
- Amino acids released from breakdown of proteins and converted into a-keto acids during amino acid metabolism
What is the Cori Cycle?
the metabolic pathway where lactate produced by anaerobic glycolysis in exercisng muscle cells is transported to the liver to be converted back to glucose
What happens in step 1 of the cori cycle?
glucose from blood is taken up by intensely exercising skeletal muscle
What happens in step 2 of the cori cycle?
anaerobic glycolysis converts glucose to lactate
What happens in step 3 of the cori cycle?
lactate diffuses into the blood and is taken up by the liver
What happens in step 4 of the cori cycle?
liver synthesizes glucose from lactate via gluconeogenesis
What happens in step 5 of the cori cycle?
glucose is released back into the blood
How many reactions is Gluconeogenesis comprised of?
11 reactions, including:
- 7 reversible reactions of glycolysis
- 4 reactions unique to gluconeogenesis
What are the 4 unique reactions to gluconeogenesis?
- conversion of pyruvate to oxaloacetate
- formation of phosphoenolpyruvate
- dephosphorylation of fructose 1,6-bisphosphate
- dephosphorylation of glucose 6-phosphate
What is pyruvate carboxylated by? Where does this take place?
pyruvate carboxylase in the mitochondria of liver and kidney cells
What does pyruvate carboxylase use as a coenzyme?
biotin
What occurs in step 1 of carboxylation of pyruvate?
hydrolysis of ATP to ADP powers the formation of an enzyme-biotin-CO2 intermediate
What occurs in step 2 of carboxylation of pyruvate?
CO2 is transferred to pyruvate generating oxaloacetate and release the enzyme-biotin complex
What is pyruvate carboxylase activated by?
acetyl-CoA
What is pyruvate carboxylase inhibited by?
ADP
What is oxaloacetate in the mitochondria reduced to to cross the mitochondrial membrane?
- maltate
- NADH is oxidized to NAD+
What happens after maltate crosses into the cytosol?
it is oxidized back to oxaloacetate, with NADH regenerated from NAD+
What happens to oxaloacetate once in the cytosol?
it is decarboxylated and phosphorylated by PEP-carboxykinase to form phosphoenolpyruvate (PEP)
What happens to PEP in the cytosol?
it undergoes reversible reactions that are part of glycolysis until it is converted to fructose 1,6-bisphosphate
What occurs during the dephosphorylation of fructose 1,6-bisphosphate?
phosphate is removed from fructose 1,6-bisphosphate by fructose 1,6-bisphosphatase
What is fructose 1,6-bisphosphatase inhibited by?
high levels of AMP and fructose 2,6-bisphosphate
What is fructose 1,6-bisphosphatase activated by?
citrate and ATP
What is the product of PFK-2?
fructose 2,6-bisphosphate
What is PFK-2? What is it regulated by?
a bifunctional protein that is regulated by the hormones insulin and glucagon
What occurs during the dephosphorylation of glucose 6-phosphate?
- glucose 6-phosphate is transported to the lumen of the ER and dephosphorylated by glucose 6-phosphatase
- once formed, glucose is shuttled back to the cytoplasm
What does gluconeogenesis use/produce?
- uses 2 pyruvate, 4 ATP, 2 GTP, and 2 NADH
- produces 1 glucose molecule
How do glucagon levels stimulate gluconeogenesis?
- decreases fructose 2,6-bisphosphate which activates fructose 1,6-bisphosphatase and inhibits PFK-1
- leads to phosphorylation of pyruvate kinase, inactivating it which diverts PEP to glucose synthesis
How does substrate abailability regulate gluconeogenesis?
in an energy poor state, proteins are broken down and amino acids provide substrates for gluconeogenesis
How does allosteric activation of pyrucate carboxylase by acetyl-CoA regulate gluconeogenesis?
during starvation, breakdown of lipids results in increased acetyl-CoA
Where does glycogen synthesis and degradation occur?
in the cytoplasm of cells
Where is glycogen stored?
in the liver and skeletal muscle
What does liver glycogen do?
maintains blood glucose levels, primarily during the initial stages of fasting
What does muscle glycogen do?
functions as a fuel reserve for ATP synthesis during muscle contraction; muscle cells do not share their glycogen with the rest of the body
Describe the structure of glycogen.
- branched-chain homopolysaccharide made up of a-D-glucosse held together by glycosidic bonds
Describe the formation of glycosidic bonds of glycogen.
- primary bond is an a(1-4) linkage
- after 8-10 glucose moecules, there is a branch formed by an a(1-6) linkage
What is the source of all glucose molecules added to glycogen?
a-D-glucose attached to uridine diphosphate (UDP)
Which two enzymes catalyze glycogen synthesis
- glycogen synthase: makes a(1-4) linkages
- branching enzyme: makes a(1-6) linkages
What occurs at the beginning of flycogen synthesis (glycogenesis)?
- UDP-glucose is synthesized from glucose 1-phosphate and UTP by UDP-glucose pyrophosphorylase
What is UDP-glucose? How does it act in glycogensis?
- an activated, high energy form of glucose
- acts as another source of energy, like ATP
What occurs in the middle of glycogenesis?
glycogen synthase requires a primer fragment of glycogen; in the absence of a glycogen fragment, glycogenin can accept glucose molecules on the -OH of a Tyr side chain
What occurs at the end of glucogenesis?
- chain elongation proceeds with the transfer of the glucose from UDP-glucose to the non-reducing end of the growing chain
- chain branching is catalyzed by branching enzyme, which transfers a chain of 6-8 glucose by breaking a(1-4) bonds and forming an a(1-6) link
What occurs during glycogen degradation (glycogenolysis)?
- produces glucose 1-phosphate from breaking a(1-4) glycosidic bonds and glucpse from breaking a(1-6) glycosidic bonds
Which two enzymes do degradation of glycogen need?
- glycogen phosphorylase
- debranching enzyme
What does glycogen phosphorylase do?
cleaves a(1-4) linkages
What does debranching enzyme do?
- glycosol (4,4) transferase activity removes the out 3 or 4 glucose molecules from the branch to the straight chain forming a new a(1-4) bond
- a(1,6) glucosidase removes the remaining glucose
What is synthesis of glycogen stimulated by?
high levels of glucose and ATP (well-fed state)
What is breakdown of glycogen stimulated by?
low glucose and energy levels (fasted state)
