L14 - Glucose Metabolism: Glycogen and Glycolysis Flashcards
Structure of Glucose:
- Monosaccharide
- 10g in plasma
- osmotically active (can’t be stored in large amounts)
- immediate energy source
Structure of Glycogen:
- Polysaccharide
- 400g in tissue stores
- Low osmolarity so can be stored in animals. Energy storage in plants is starch.
- Medium term fuel source
Role of Glycogen in Liver: Glucose Homeostasis
It regulates blood glucose.
Liver uses insulin and glucagon to do this.
Insulin used when high glucose.
Glucagon used when low glucose.
Store glucose as glycogen when blood glucose is high by converting glucose to glycogen when insulin present.
Release glucose when low blood glucose by converting glycogen to glucose when glucagon present.
Glycogen–>Glucose 6-phosphate
Glucose 6-phosphate–> Glucose + Pi
100-120g glycogen in liver
Role of Glycogen in Muscle: Fuel for Exercise
Regulation of glycogenolysis is sensitive to energy needs of tissue.
- Sensitive to adrenaline - energy boost for fight-or-flight response.
- Calcium released in cells due to neuronal signalling for muscle contraction.
- AMP - allosteric regulators for glycogen breakdown
- ATP
Glycogen–> Glucose–> Lactate
Glycogen synthesis:
Enzyme, basic reaction, requirements, and summary
Main enzyme: GLYCOGEN SYNTHASE Requires energy (ATP hydrolysis) Proceed via an 'activated' intermediate: UDP glucose
UDP - used as an energy carrier instead of ATP
SUMMARY: Glycogen synthase
Uses UDP-Glucose which attaches glucose at end of glycogen chain.
Branching enzyme used to form a-1,6 bonds for branching on glycogen.
Glycogen synthesis: THE PATHWAY
Glucose–>Glucose 6-phosphate
HEXOKINASE (muscle) and GLUCOKINASE (liver)
ATP converted to ADP
G6-P–>Glucose 1-phosphate
PHOSPHOGLUCOMUTASE - only reversible reaction.
G1-P–>UDP Glucose
UDP GLUCOSE PYROPHOSPHORYLASE
UTP added and Pi released
UDP Glucose + Glycogen primer molecule = Glycogen + UDP
GLYCOGEN SYNTHASE
Glycogen breakdown:
Enzyme, basic reaction, requirements, and summary
Main enzyme: GLYCOGEN PHOSPHORYLASE Phosphorylysis using Pi (not ATP) Final product in liver: Glucose Final product in muscle: Glucose 6-phosphate G6-P enters glycolysis pathway.
SUMMARY: Glycogen Phosphorylase
Uses phosphate ion to separate glucose from glycogen
Glycogen breakdown: THE PATHWAY
Glycogen–>Glucose 1-phosphate
GLYCOGEN PHOSPHORYLASE
Add Pi
G1-P + glycogen chain(shorter) = glucose 6-phosphate
PHOSPHOGLUCOMUTASE
(Go to glycolysis in muscle as it can’t do next reaction as it doesn’t have correct enzyme.)
G6-P–> Glucose + Pi
GLUCOSE 6-PHOSPHATASE (liver and kidney)
H2O added
Glycolysis:
Function, basic reaction, location
Function:
- Synthesis of ATP
- Use glucose as fuel from: sugar and starch from diet, breakdown of stores glycogen in liver, recycled glucose (from lactic acid, A.A or glycerol by gluconeogenesis) –> non-carbohydrates can make glucose
Location:
Occurs in Cytosol
Basic reaction:
Glucose (6C) to 2xPyruvate (3C)
10 reactions split to 4 stages:
- Activation (using ATP) = reaction 1-3
- Splitting the 6C sugar in half = reaction 4+5
- Oxidation (remove 2H atom) = reaction 6
- ATP synthesised = reaction 7-10
Glycolysis: THE PATHWAY
D-glucose–> G6-P
HEXOKINASE/GLUCOKINASE
Uses ATP giving ADP
G6-P to Fructose 6-phosphate
PHOSPHOHEXOSE ISOMERASE
F6-P–> Fructose 1,6-bisphosphate
PHOSPHOFRUCTOKINASE
Uses ATP giving ADP
F1,6-BP to dihydroxyacetone phosphate or glyceraldehyde 3-phosphate (interconvert between each other with TRIOSE PHOSPHATE ISOMERASE)
ALDOLASE
GA3-P to 1,3-Bisphosphoglycerate
GLYCERALDEHYDE 3-PHOSPHATE DEHYDROGENASE
(Pi + NAD+ = NADH + H+)
1,3-BPG to 3-phosphoglycerate
3-PHOSPHOGLYCERATE KINASE
Add ADP and get ATP
3-PG to 2-phosphoglycerate
PHOSPHOGLYCERATE MUTASE
2-PG to phosphoenolpyruvate
ENOLASE
removes H2O
PEP–> Pyruvate
PYRUVATE KINASE
Add ADP and get ATP
to = reversible reactions
–> = irreversible reactions
ATP synthesis by substrate level phosphorylation
1 glucose to 2 Pyruvate
Early stage uses 2 ATP:
1. D-Glucose to Glucose 6-phosphate
IRREVERSIBLE
- Fructose 6-Phosphate to Fructose 1,6-
Bisphosphate
IRREVERSIBLE
Later stages make 4 ATP:
1. 1,3-Bisphosphoglycerate to
3-phosphoglycerate
REVERSIBLE
- Phosphoenolpyruvate to Pyruvate
IRREVERSIBLE
Makes 2 ATP per Pyruvate so 4 ATP per glucose.
NET YIELD: 2 ATP
Regeneration of NAD+ from NADH in aerobic and anaerobic conditions:
Aerobic: Enters ETC as NADH and carries electrons and hydrogen. So converted back to NAD+
Anaerobic: Pyruvate converted to lactate using NADH and forming NAD+
Lactate dehydrogenase allows regeneration of NAD+ in muscle
Pyruvate + NADH + H+ = L-Lactate + NAD+
Forward reaction is in muscle with the use of LACTATE DEHYDROGENASE.
Backward reaction is in liver where lactate is converted back to pyruvate and allows glycolysis to occur.
Specialised functions of glycolysis in tissues: (red blood cells, skeletal muscle and brain)
Red blood cells:
Glycolysis is the only pathway for ATP production as it has no mitochondria.
Skeletal Muscles:
ATP production required for intense exercise so glycolysis important.
Brain:
Glycolysis in brain is a major source of ATP (cannot use fats as fuel).
Regulation of glycogen metabolism and glycolysis:
Both pathways under:
- allosteric control
- hormonal control
Glycogen metabolism:
-control by glucagon (low blood glucose converts glycogen to glucose).
Receptors in liver and muscle.
- adrenaline (for fight-or-flight response)
Receptor in muscle.
Fate of Pyruvate:
Pyruvate to lactate when no oxygen or mitochondria.
Pyruvate to ethanol in microorganisms only.
Pyruvate to Acetyl CoA.
Acetyl CoA to fatty acids if excess calories intake.
Acetyl CoA to citric acid cycle when oxygen present.
Citric acid cycle to CO2 when oxygen present.