BioChem CH17 E2

what is gluconeogenesis and what is the major site

-its the synthesis of glucose from pyruvate
-major site is the liver (can occur in kidney)
-important during fasting or starvation since glucose is the primary fuel for the brain and only fuel for red blood cells

what does the gluconeogenic pathway convert

-convert pyruvate into glucose (80% reverse of what glycolysis does; set of enzymes are different)
-pyruvate can be formed from muslce-derived lactate in the liver by lactate dehydrogenase

what can the carbon skeletons of some amino acids and glycerol be converted into

-carbon skeletons: converted into gluconeogenic intermediates
-glycerol: dihyroxyacetone phosphate which can be processed by gluconeogenesis or glycolysis

what molecule is different in gluconeogeneis

-oxaloacetate
-reaction is in reverse of glycolysis (just enzymes are different)

why is gluconeogenesis not a complete reversal of glycolysis

-there are 3 irreversible steps in glycolysis that must be bypassed in gluconeogenesis

what 2 enzymes are required for the formation of phosphoenolpyruvate from pyruvate

-pyruvate carboxylase and phosphoenolpyruvate carboxykinase

the conversion of pyruvate into phosphoenolpyruvate begins with?

the formation of oxaloacetate (with enzyme of pyruvate carboxylate)
-pyruvate carboxylase requires the vitamin biotin as a cofactor
-occurs in three stages

where does the formation of oxaloacetate by pyruvate carboxylase occur

-in the mitochondria
-oxaloacetate is reduced to maltate and transported into the cytoplasm, where it is reoxidized to oxaloacetate with the generation of cytoplasmic NADH
-PEP is then synthesized from oxaloacetate by phospheonolpyruvate carboxykinase

when is phosphoenolpyruvate metabolized

-metabolized by the enzymes of glycolysis in the reverse direction until the next irreversible step, the hydrolysis of fructose 1,6-biphosphate
-enzyme catalyzing this reaction is fructose 1,6 biphosphatase, an allosteric enzyme

what is an important control point

-the generation of free glucose
-this occurs only in the liver and is the final step of gluconeogenesis

where is glucose 6-phosphate transported to

-transporter into the lumen of the endoplasmic reticulum
-it is an integral membrane on the inner surface of the endoplasmic reticulum, catalyzes the formation of glucose from glucose 6-phosphate

what barrier prevents glycolysis from simply running in reverse to synthesize glucose? How is this barrier overcome in gluconeogenesis?

-large delta G values
-there are enzymes used to made steps to bypass irreversible steps
-uses 6 molecules of NTPs`

how to determine whether glycolysis or gluconeogenesis will be more active

-if ATP is needed, glycolysis predominates
-if glucose is needed, gluconeogenesis is favored

what are the rates of glycolysis and gluconeogenesis adjusted for in the liver? what is the key regulator of glucose metabolism in the liver?

-adjusted to maintain blood-glucose levels
-fructose 2,6-bisphosphate (stimulates phosphofructokinase and inhibits fructose 1,6-biphosphatase)

what is bifunctional enzyme

-when two molecules are located on the same polypeptide chain

what happens when blood glucose levels are low

the hormone glucagon is secreted
-the glucagon signaling pathway leads to the phosphorylation of the bifunctional enzyme, which inhibits the kinase and stimulates the phosphatase

what are the regulatory means that prevent high levels of activity in glycolysis and gluconeogenesis simultaneously? What would be the result if both pathways functioned rapidly at the same time?

-glucagon signaling pathway
-they would cancel each other

what normally inhibits gluconeogenesis

-insulin
-in type 2 diabetes, insulin fails to act, condition called insulin resistance
-the enzymes of gluconeogenesis (PEPCK) are active, leading to abnormally high levels of blood glucose

what is the Cori cycle

-muscle and liver display interorgan cooperation in a series of reactions
-lactate produced by the muscle during contraction is released into the blood
-liver removed the lactate and converts it into glucose, which can be released into the blood