Glycogen Metabolism and Gluconeogenesis Flashcards
Glycogen structure
polymer of alpha 1->4 linkages with alpha 1->6 branch points every 8-14 residues
Glycogen phosphorylase
-removes 1 residue at a time from nonreducing end of glycogen
-attacks inorganic Pi
-yields Glucose-1-Phosphate which can be converted to G6P
Step 1
Formation of an Enzyme-Pi glycogen complex
enzyme binds to PLP cofactor whose phosphate group acts as a general acid-base catalyst
Step 2
Terminal glycosyl is converted to oxonium ion during C1-O1 bond cleavage via proton transfer through Pi from PLP phosphate
Step 3
Oxonium interacts with Pi forming the alpha conformation of G1P
Glycogen debranching enzyme purpose
to resolve limit branch structures so GP can continue to degrade linear regions
Glycogen debranching enzyme activities
-alpha 1-4 transglycolase transfers trisaccharide to nonreducing end
-Alpha 1-6 glucosidase cleaves remaining glucose by hydrolysis to release free glucose
Phosphoglucomutase
carries out a double phosphorylation to convert G1P to G6P for use in glycolysis
In vivo, glycogen breakdown is ______ favorable while glycogen synthesis is not
thermodynamically
UDP-Glucose Phosphorylase
-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
UDP is a good…
Leaving group
Glycogen synthase
-UDP departure generates electrophilic oxonium at C1 that can be attacked by C4 hydroxyl on nonreducing end of glycogen chain
Branching enzyme
required to create branches in glycogen
G6 Phosphatase deficiency
Tissue: liver
Name: Von Gierkes
Glycogen structure: normal
Glycogen synthase deficiency
Tissue: Liver
Glycogen structure: normal but deficient quantity
How are glycogen synthase and glycogen phosphorylase regulated?
Reciprocally regulated both covalently and allosterically. Covalent regulation occurs via phosphorylation and dephosphorylation
Reciprocal enzyme regulation
Protein kinase A
Activates by phosphorylation
Phosphorylase Kinase
Phosphorylates at Ser 14 residue
Glycogen phosphorylase
Dephosphorylated by
Protein phosphatase I
dephosphorylates
phosphorylase kinase
2 enzymes needed to bypass pyruvate kinase catalyzed step of glycolysis
pyruvate carboxylase and PEP carboxykinase
_____ and ______ protein kinase A to begin glycogen breakdown
epinephrine and glucagon
Phosphoenol pyruvate formation
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
Pyruvate carboxylase
-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
Reaction of pyruvate carboxylase
-ATP cleaved, forms a carboxyphosphate intermediate
-CO2 transfer to biotin is exergonic
CO2 transfer to biotin
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
PEPCK reaction
-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
Which stages are shared between glycolysis and gluconeogenesis?
Triose
After formation of Fructose-1,6-Bisphosphate,____ is required to bypass ____ reaction
Fructose-1,6-Bisphosphatase, phosphofructokinase I
F1,6BPase allosterically inhibited by
AMP and Fructose-2,6-Bisphosphate
Final step of gluconeogenesis
-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