Glycogen Metabolism, Synthesis, and PPP Flashcards
What is glycogen?
Glycogen is a polysaccharide consisting of a-1,4-linked glucose with a-1,6- branched glucose every ~ 10 residues.
Glycogen is a readily mobilized form of glucose that is stored mainly in liver and muscle.
What is the process that cleaves glycogen?
Phosphorolytic Cleavage
Does cleaving glycogen require ATP?
No
What is the final product after cleaving glycogen?
Glucose-1-Phosphate
Where does degredation of glycogen start?
non-reducing ends (free ends)
What is the first step of glycogen degradation?
What is the enzyme?
Phosphorolytic Cleavage
Glycogen Phosphorylase
What happens during Phosphorolytic Cleavage?
Glycogen Phosphorylase adds an inorganic phosphate to the non-reducing end of glycogen to form G-1-P. Resulting glycogen polymer is one unit shorter.
What happens to the G-1-P, and what enzyme is responsible?
Converted into G-6-P by Phosphoglucomutase
How does Phosphoglucomutase work?
This enzymes functions by covalently modifying a serine residue which exchanges phosphate w/ G-1-P to make a G-1,6-BP intermediate prior to a back exchange to the 6 position to make G-6-P

What happens to the G-6-P, and what enzyme is involved?
It gets converted into glucose by Glucose-6-Phosphatase
What are the two enzymes needed to deal with a-1,6 branching?
Transferase
a-1,6 Glucosidase
Where does this occur?
glycogen metabolism is used during heavy exercise for anaerobic respiration
G-6-P goes directly into glycolysis
Muscle
Where does this occur?
glycogen metabolism is designed for glucose export into blood
G-6-P must be converted to glucose for export
Liver
What is the function of transferase?
Removes three of the four residues left at the branch point by glycogen phosphorylase and catalyzes their polymerization onto the unbranched strand (a-1,4-linkages)
Removes them from branch and places them on the main line
What is the function of a-1,6-glucosidase?
Removes the final a-1,6 glucose from the branch
Regulation of glycogen metabolism occurs through ____.
Signal Transduction
Of Glycogen Phosphorylase A and Glycogen Phosphorylase B, which is active and which is inactive?
A is active and phosphorylated,
B is inactive and de-phosphorylated
Both have T and R states
How is Glycogen Phosphorylase A regulated?
The a form (which is nearly all in the R state) in muscle is regulated by phosphorylation/dephosphorylation of b to a
How is Glycogen Phosphorylase B regulated?
The b form is downregulated by ATP and G-6-P (conversion to T form) and upregulated by AMP (conversion to R form).
What is needed for glycogen synthesis?
A high energy intermediate glucose donor, uridine diphosphate glucose (UDP-glucose).
How is UDP-glucose formed?
From a reaction of UTP with G-1-P
What is the reaction that forms UDP-Glucose, and what is the enzyme involved?
UTP + G-1-P to UDP-G + PPi (pyrophosphate from UTP)
UDP glucose pyrophosphorylase
Is it possible to reverse the formation of UDP-Glucose? What causes this?
Reaction is made irreversible by inorganic pyrophosphatase that takes PPi to 2Pi
What Molecule is this?

Glucose
What Enzyme is this?

Hexokinase
What Molecule is this?

G-6P
Glucose-6-Phosphate
What Molecule is this?

G-1P
Glucose-1-Phosphate
What Enzyme is this?

Phosphoglucomutase
What Molecule is this?

G-6P
Glucose-6-Phosphate
What Molecule is this?

Glucose-1-Phosphate
What Molecule is this?

UTP
What Molecule is this?

UDP-Glucose
What Enzyme is this?

UDP-Glucose Phosphorylase
What Molecule is this?

UDP-Glucose
What Molecule is this?

Glycogen
What Molecule is this?

UDP
What Molecule is this?

Glycogen (1 Unit More)
What Enzyme is used in this reaction?

glycogen synthase
What is the Glycogen Primer, the protien at the center of all glycogen that the branches grow off of?
Glycogenin protein
An enzyme with _____activity adds UDP-glucose to a tyrosine
glucotransferase
Initial catalysis of an octamer of glucose units is necessary to act as the substrate for____
glycogen synthase
What is the function of branching, and what enzyme is responsible for it?
Branching serves to increase solubility and increases rate of synthesis and degradation by forming multiple termini.
Branching Enzyme
What regulates Glycogen Synthesis, and how?
Glycogen synthase, interconversion of a and b forms through phosphorylation
What stimulates the conversion of Glycogen Synthase between a and b forms?
PKA does phosphorylation of Glycogen Synthase Kinase (GSK3) and is controlled by glucagon and epinephrine (cell needs energy so turn off synthesis).
What is the role of insulin in Glycogen Synthesis?
Insulin promotes glucose uptake and phosphorylation by the cell as well as inactivation of GSK3 to inhibit phosphorylation of glycogen synthase and activate glycogen synthesis.
What is the PPP?
The Pentose Phosphate Pathway
What are the three roles of the PPP?
- Important source of NADPH (biosynthetic reducing power for fat synthesis)
- Interconversion of 5 Carbon sugars from diet to useful 3C and 6C sugars that can be directed into glycolysis.
- Synthesis of important pentose sugars needed for DNA and RNA synthesis.
What is the overall reaction for PPP?
G-6-P + 2NADP+ ——-> Ribulose-5-P + 2NADPH + 2CO2
What is Phase 1 of the PPP, and what happens?
Oxidative Phase
NADPH is formed through two sequential 2 e- oxidations
What is Phase 2 of the PPP, and what happens?
Non-oxidative Phase
Interconversion of phophoryated sugars
What happens in step 1 of the PPP, and what is the enzyme involved?
Oxidation of the C1 hemiacetal to a lactone (cyclic ester) the 2e- are transferred to NADP to make NADPH.
G-6-P dehydrogenase

What happens in step 2 of the PPP, and what is the enzyme involved?
Hydration reaction and ring opens the lactone substrate to the carboxylic acid (a sugar acid).
lactonase

What happens in step 3 of the PPP, and what is the enzyme involved?
Oxidative decarboxylation to generate the 5C product (a ketose) as well as another NADPH.
6-phosphogluconate dehydrogenase

What step of the PPP is this, and what enzyme is used?

1
Glucose 6-Phosphate Dehydrogenase
What step of the PPP is this, and what enzyme is used?

2
Lactonase
What step of the PPP is this, and what enzyme is used?

3
6-Phosphogluconate Dehydrogenase
What is this Molecule?

Glucose 6-Phosphate
What is this Molecule?

6-Phosphoglucono-(sigma)-lactone
What is this Molecule?

6-Phosphogluconate
What is this Molecule?

Ribulose 5-Phosphate
What is this Enzyme?

Glucose 6-Phosphate Dehydrogenase
What is this Enzyme?

Lactonase
What is this Enzyme?

6-Phosphogluconate Dehydrogenase
What is this molecule?

Ribulose 5-Phosphate
ketose
What is this Molecule?

Ribose 5-Phosphate
aldose
What is this Enzyme?

Phosphopentose Isomerase
Why is Ribose necessary in cells?
- Ribose-5-P is a precursor to sugars needed to make RNA, DNA, ATP, NADH, FAD, coenzyme A etc.
- Although Ribose-5-P is an important biosynthetic intermediate, the body has a greater need for NADPH.
- Under these conditions (need for NADPH but not Ribose-5-P) the body can convert this 5C sugar into 3C and 6C sugars that feed into glycolysis.
What are the three basic reactions in the conversion of 5C sugars?
C5 + C5 to C3 + C7
C3 + C7 to C6 + C4
C4 + C5 to C6 + C3
Total:3C5 to 2C6 + C3
What is this Molecule?

Ribose 5-Phosphate
What Molecule is this?

Ribulose 5-Phosphate
What Molecule is this?

Xylulose 5-Phosphate
What Enzyme is this?

Phosphopentose Isomerase
What Enzyme is this?

Phosphopentose Epimerase
What are these two Molecules?

Xylulose 5-P
Ribose 5-P
What are these two Molecules?

G 3-P
Sedoheptulose 7-P
What are these two Molecules?

Fructose 6-P
Erythrose 4-P
What are these two Molecules?

Xylulose 5-P
Erythrose 4-P
What are these two Molecules?

G 3-P
Fructose 6-P
What is this Enzyme?

Transketolase
What is this Enzyme?

Transaldolase
What is this Enzyme?

Transketolase
How is the PPP regulated?
- The use of G-6-P is determined by 2 basic needs, energy (ATP) and biosynthetic reducing power (NADPH) for making fat.
- Both of these molecules regulate glycolysis or PPP.
- In the oxidative part of PPP, the first dehydrogenase is essentially irreversible, thus the logical regulatory point.
- At low [NADP+] the three enzymes in the oxidative part of PPP have low activity (NADPH competes with binding to enzyme, is thus a competitive inhibitor).
What three things does the fate of G-6-P depend on?
Need for NADPH
Need for ATP
Need Ribose-5-P
Under different scenarios G-6-P is routed to which different pathways?
To Ribose-5-P
To recycling mode for NADPH formation
To pyruvate (ATP)