Glycogen Metabolism and Gluconeogenesis

Question 1

Glycogen structure

Answer 1

polymer of alpha 1->4 linkages with alpha 1->6 branch points every 8-14 residues

Question 2

Glycogen phosphorylase

Answer 2

-removes 1 residue at a time from nonreducing end of glycogen
-attacks inorganic Pi
-yields Glucose-1-Phosphate which can be converted to G6P

Question 3

Step 1

Answer 3

Formation of an Enzyme-Pi glycogen complex
enzyme binds to PLP cofactor whose phosphate group acts as a general acid-base catalyst

Question 4

Step 2

Answer 4

Terminal glycosyl is converted to oxonium ion during C1-O1 bond cleavage via proton transfer through Pi from PLP phosphate

Question 5

Step 3

Answer 5

Oxonium interacts with Pi forming the alpha conformation of G1P

Question 6

Glycogen debranching enzyme purpose

Answer 6

to resolve limit branch structures so GP can continue to degrade linear regions

Question 7

Glycogen debranching enzyme activities

Answer 7

-alpha 1-4 transglycolase transfers trisaccharide to nonreducing end
-Alpha 1-6 glucosidase cleaves remaining glucose by hydrolysis to release free glucose

Question 8

Phosphoglucomutase

Answer 8

carries out a double phosphorylation to convert G1P to G6P for use in glycolysis

Question 9

In vivo, glycogen breakdown is ______ favorable while glycogen synthesis is not

Answer 9

thermodynamically

Question 10

UDP-Glucose Phosphorylase

Answer 10

-phosphoryl O of G1P attacks alpha phosphorus atom of UTP to generate UDP-Glucose
-Lambda and beta phosphate groups are released as pyrophosphate which is then hydrolyzed by phosphatase
-UDP-Glucose is activated and donates glucose to growing glycogen chain

Question 11

UDP is a good…

Answer 11

Leaving group

Question 12

Glycogen synthase

Answer 12

-UDP departure generates electrophilic oxonium at C1 that can be attacked by C4 hydroxyl on nonreducing end of glycogen chain

Question 13

Branching enzyme

Answer 13

required to create branches in glycogen

Question 14

G6 Phosphatase deficiency

Answer 14

Tissue: liver
Name: Von Gierkes
Glycogen structure: normal

Question 15

Glycogen synthase deficiency

Answer 15

Tissue: Liver
Glycogen structure: normal but deficient quantity

Question 16

How are glycogen synthase and glycogen phosphorylase regulated?

Answer 16

Reciprocally regulated both covalently and allosterically. Covalent regulation occurs via phosphorylation and dephosphorylation

Question 17

Reciprocal enzyme regulation

Answer 17

Protein kinase A
Activates by phosphorylation
Phosphorylase Kinase
Phosphorylates at Ser 14 residue
Glycogen phosphorylase
Dephosphorylated by
Protein phosphatase I
dephosphorylates
phosphorylase kinase

Question 18

2 enzymes needed to bypass pyruvate kinase catalyzed step of glycolysis

Answer 18

pyruvate carboxylase and PEP carboxykinase

Question 19

_____ and ______ protein kinase A to begin glycogen breakdown

Answer 19

epinephrine and glucagon

Question 20

Phosphoenol pyruvate formation

Answer 20

1) Form oxaloacetate with ATP catalyzed by pyruvate carboxylase
2) Decarboxylation of oxaloacetate is favorable and helps drive PEP formation
3) GTP used as phosphoryl group donor catalyzed by PEP carboxylase

Question 21

Pyruvate carboxylase

Answer 21

-metabolically irreversible
-fixes O2 and forms oxaloacetate
-mitochondrial enzyme allosterically activated by acetyl coa accumulation from fatty acid oxidation which signals the liver to direct pyruvate to oxaloacetate for gluconeogenesis
-biotin cofactor

Question 22

Reaction of pyruvate carboxylase

Answer 22

-ATP cleaved, forms a carboxyphosphate intermediate
-CO2 transfer to biotin is exergonic

Question 23

CO2 transfer to biotin

Answer 23

pyruvate enters active site and releases CO2 from biotin as it accepts a proton from pyruvate. pyruvate is now in enolate form which carries out a nucleophilic attack on CO2

Question 24

PEPCK reaction

Answer 24

-CO2 intergrated into pyruvate to make oxaloacetate released via decarboxylation, creating an enol
-Enol compound is a good substrate for phosphorylation by GTP creating PEP

Question 25

Which stages are shared between glycolysis and gluconeogenesis?

Answer 25

Triose

Question 26

After formation of Fructose-1,6-Bisphosphate,____ is required to bypass ____ reaction

Answer 26

Fructose-1,6-Bisphosphatase, phosphofructokinase I

Question 27

F1,6BPase allosterically inhibited by

Answer 27

AMP and Fructose-2,6-Bisphosphate

Question 28

Final step of gluconeogenesis

Answer 28

-G6Pase produces free glucose
-Located in ER membrane and is most strongly expressed in liver
-Transports G6P into ER where the active site hydrolyzes the phosphate