Glycogenolysis & Gluconeogenesis

Question 1

Glycogenolysis

Start substrate & end product
Enzymes
Purpose

Answer 1

Glycogen –> Glucose

Enzymes:

• Glycogen phosphorylase
• debranching enzyme
• phosphoglucomutase
• glucose-6-phosphatase

Purpose:
1. provide glucose for brain and RBCs during short-term fast (5-24 hrs)

2. Provide glucose for energy and increased beta oxidation (muscle only)

Question 2

Glycogen Phosphorylase

Function
energy source
Coenzyme

Answer 2

Function:

• RATE LIMITING
• breaks glycogen chain to produce a single G1P molecule
• cannot work w/in 4 residues of 1,6 bond

Energy source:
inorganic phosphate, NOT ATP

Coenzyme: 
pryidoxal phosphate (b6)

Question 3

Debranching Enzyme

2 Parts: Function of each

Answer 3

1. Transferase:
   - works on 1,4 bonds
   - removes outer 3 of last 4 molecules at branch point
   - adds them to another chain
2. Glucosidase:
   - works on 1,6 bond
   - hydrolyse bond at branch point using water
   - Creates free glucose molecule for export to blood from GLUT2

Question 4

Phosphoglucomutase & Glucose-6-Phosphatase

Answer 4

1. Phosphoglucomutase:
   - rearranges G1P to G6P
2. G6Pase
   - removes phosphate to produce glucose
   - only found in liver and kidney cortex
   - transported to blood via GLUT2

Question 5

Regulation of Glycogen Metabolism

Insulin, Glucagon, Epinephrine

Answer 5

Insulin: dephosphorylation

• glycogen synthase active
• promotes glycogenesis
• Glycogen phosphorylase inactive

Glucagon: phosphorylation (via PKA)

• Glycogen phosphorylase active, promotes glycogenolysis
• glycogen synthase inactive

Epinephrine: phosphorylation (via PKA)

• glycogen phosphorylase is active, glycogenolysis
• can override insulin signaling by inhibiting insulin release

Question 6

Gluconeogenesis

Start & End
Enzymes
Energy Carriers
Purpose

Answer 6

Amino Acids, Lactate, Glycerol –> pyruvate –> glucose

Enzymes:

• Pyruvate Carboxylase (PC)
• Phosphoenolpyruvate Carboxykinase (PEPC)
• Fructose 1,6 bisphosphatase (FBPase-1)
• Glucose-6-phosphatase (G6Pase)

Energy Carriers:

• 4 ATP
• 2 GTP (cyto)
• 2 NADH (cyto)

Purpose:

1. Provide glucose for brain & RBCs
2. Utilize lactate and provide glucose for Cori Cycle

Question 7

Pyruvate Carboxylase

Answer 7

Pyruvate (mito) –> OAA (mito)–>malate (mito) –> OAA (cyto)

• Requires biotin coenzyme
• Activated by Acetyl CoA

Question 8

PC vs PDHC

Fed State

Answer 8

• glycolysis produces large amounts of pyruvate which can be metabolized to OAA or ACoA
• ACoA inhibits its own synthesis by PDHC
• ACoA increases activity of PC
• Results in equal levels of OAA and ACoA

Question 9

PC vs PDHC

Fasting state

Answer 9

• large amounts of ACoA, NADH, and FADH2 produced from beta oxidation
• amino acids and lactate used to synthesize pyruvate
• high [ACoA] activates PC, but inhibits PDHC causing pyruvateto be metabolized to OAA (mito)

Question 10

PEPCK

Answer 10

OAA (cyto) to PEP

Question 11

FBPase-1

Answer 11

Fructose 1,6 bisphosphate –> F6P

• RATE LIMITING STEP
• not regulated by phosphorylation
• Regulated by high levels of F2,6BP, inhibits FBPase-1, activates PFK-1

Question 12

F2,6BP

Answer 12

Inhibits FBPase-1

Activates PFK-1

High I/G: high [F2,6BP]
Low I/G: low [F2,6BP]

Question 13

G6Pase

Answer 13

F6P –> Glucose

Dephosphorylates G6P to Glucose

Glucose released from GLUT2 in liver to bloodstream

GLUT2 not insulin regulated, always available to transport glucose across concentration gradient

Question 14

Cori Cycle

Answer 14

Pyruvate–>lactate

shifts metabolic burden from RBCs or exercising muscles to liver

anaerobic glycolysis of glucose in muscle and RBCs

forms lactate to be used by liver for gluconeogenesis