Chapter 28 Gluconeogenesis Flashcards
List the precursors of gluconeogenesis and where they come from
- lactate: anaerobic glycolysis (RBC & muscle)
- glycerol: released from adipose stores of triacylglycerol
- amino acids: especially alanine, from degradation of muscle protein
What makes the carbons of glycerol gluconeogenic?
They form dihydroxyacetone phosphate (DHAP), a glycolytic intermediate.
Is gluconeogenesis the reverse of glycolysis? Why or why not?
Glycolysis has three highly exergonic steps, so gluconeogenesis must use other enzymes to make glucose from pyruvate. Thus, gluconeogenesis is not the exact opposite of glycolysis.
How is the conversion of pyruvate to phosphoenolpyruvate regulated?
Pyruvate carboxylase is activated by acetyl CoA. PEPCK is induced (transcription and translation increased) by cAMP induced by glucagon (fasting) or by epinephrine (stress). CREB (cAMP response element binding protein) activates transcription. When glucagon is elevated, liver pyruvate kinase is phosphorylated (involving PKA from GPCR cascade). This prevents PEP from reconversion to pyruvate, and avoids a futile cycle. PKA phosphorylates and activates phosphorylase kinase, and phosphorylates and INactivates glycogen syntase. Phosphorylase kinase activates phosphorylase, which breaks down glycogen.
What is the primary source of glucose at the 12 hour mark of a fast?
glycogenolysis
What 2 tissues cannot synthesize their own glucose but depend on glucose for energy?
the brain and RBCs
Where does lactate come from?
Primarily RBCs, and some from muscles during exercise
When is the CO2 that was added to pyruvate to form oxaloacetatereleased?
In the reaction catalyzed by phosphoenolpyruvate carboxykinase.
What 3 sequences in gluconeogenesis are regulated?
- pyruvate –> PEP
- Fructose 1,6-bisP –> fructose 6-P
- Glucose 6-P –> glucose
When will PEP form glucose and NOT pyruvate?
When pyruvate dehydrogenase is inactive (phosphorylated and therefore, not converted to acetyl CoA), pyruvate carboxylase is active, PEP carboxykinase is induced, and/or pyruvate kinase is inactive.
What is the key difference of glucose between liver and muscle?
Insulin is greatly stimulates transport of glucose into muscle cells, BUT only slightly simulates the transport of glucose into liver cells.
What can deliver triglycerides to muscle for immediate oxidation if energy is required?
VLDL
How do glucagon blood levels respond to a high-carb meal and to a high-protein meal?
Glucagon blood levels DECREASE in response to a high-carb meal and INCREASE in response to a high-protein meal.
What type of meal keeps glucagon blood levels constant and allow insulin levels to increase?
A mixed meal containing carb, protein, and fat
When is the glycolytic enzyme, pyruvate kinase, activated and inhibited? When it is inhibited, what pathway would its inhibition help begin?
Pyruvate kinase is activated by fructose-1,6-bisphosphate and is inhibited by ATP and alanine and is inhibited by phosphorylation (glucagon and epinephrine lead to an increase in cAMP levels, which activates protein kinase A).
Pyruvate kinase inhibition contributes to the activation of gluconeogenesis.