Chapter 12: Glucose Anabolism and Regulation

Question 1

Glyconeogenesis. Draw out the reaction, including enzyme names and structures.

Need to add:
How is pyruvate introduced into the glyconeogenic pathway;
Know why gluconeogenesis is important to mammals

Answer 1

• The formation of glucose from carbon sources. These carbon sources can be lipids, glycerol, or amino acids, but NOT fatty acids. Basically, however, anything that can be broken down into an intermediate of glycolysis can be used
• It has three “bypassed” steps, which are the large free energy drop steps in glycolysis that thus would have large activation energies in gluconeogenesis. These steps are Pyr—> PEP, Fr1,6bP —-> Fr6P, and G6P—-> Glucose. All other steps are just the reverse what they would be in glycolysis.
• The first bypass step is actually two steps. First, pyruvate and bicarbonate come together in an carboxylation, with the help of pyruvate carboxylase and biotin to make oxaloacetate, and this reaction is catalyzed by ATP. Next, a decarboxylation occurs as well as a dephosphorylation of GDP to phosphorylate our compound, giving us PEP
• The second bypass step is hydrolysis by fructose 1,6 bisphosphatase
• The third bypass step is hydrolysis by glucose-6-phosphatase.
• Gluconeogenesis is inhibited by fructose 2,6 bisphosphate; this molecule is an allosteric inhibitor of fructose 1,6-bisphosphatase

Question 2

bypass reaction

Answer 2

• A reaction that undergoes a different mechanism in anabolism as in catabolism to avoid a high activation energy that makes the reverse reaction a committed step.
• In gluconeogeneis, the steps are Pyr—> PEP, Fr1,6bP —-> Fr6P, and G6P—-> Glucose

Question 3

coordinate regulation

Answer 3

f

Question 4

gluconeogenic amino acids

Answer 4

d

Question 5

fructose 2,6 bisphophate

Answer 5

• A molecule whose sole purpose is the regulate the step of Fr6P—-> Fr1,6bP in glycolysis, and its reverse reaction of Fr1,6bP—-> Fru6P in gluconeogenesis. It does so by being an allosteric activator of phospho-fructokinase-1. It is so important in the regulation of this step in glycolysis that at Fr6P levels lower than 2 mM, it is essentially an on/off switch. It acts as an inhibitor for of fructose 1,6-bisphosphatase.
• It is a cellular indicator of glucose abundance; when Fr 2,6 bP is high, glucose is high, when Fr 2,6 bP is low, glucose is low

Question 6

PFK2/FBP2

Answer 6

• These two enzymes are used in the production/breakdown of Fructose 2,6 bisphosphate
• Fructose 2,6 bisphosphate is made from the phosphorylation of Fructose 6-phosphate. This phosphorylation is carried out by phospho-fructokinase- 2 with the help of ATP
• Fructose 2,6 bisphosphate is converted back into Fr6P by fructose bisphosphatase-2, releasing an inorganic phosphate
• These “enzymes” are actually part of the same polypeptide chain that just has two different active sites
• Regulation of this large polypeptide is done through phosphorylation

Question 7

Glucagon

Answer 7

e

Question 8

PEP-CK

Answer 8

• PEP Carboxykinase
• Catalyzes the production of PeP from Oxaloacetate and GTP, leading to a decarboxylation and phosphorylation of oxaloacetate to make PEP

Question 9

pyruvate carboxylase

Answer 9

r

Question 10

What tissues perform gluconeogenesis, and how do these tissues know when to perform gluconeogeneis or glycolysis?

Answer 10

• The kidney and the liver, although it is mostly the liver
• The reactions of glycolysis and gluconeogenesis in the liver are regulated by Fructose 2,6 bisphosphate in the important regulatory step of Fr6P—-> Fr1,6bP, or vice versa in gluconeogenesis.