Glycogenesis & Lipogenesis Flashcards
Fed State:
Energy Producing, CHO Storage, Lipid Storage pathways
First priority: Glycolysis–>TCA Cycle–>ETC ATP Synthase
Second Priority: Liver Glycogenesis, CHO Storage
Third Priority: Lipogenesis (FA Synth+TAG synth), Lipid storage
Glycogenesis:
- Starting Substrate & End Product
- Enzymes Involved
- Purpose
Start/End: Blood Glucose–> Glycogen
Enzymes:
- Glucokinase, Hexokinase
- UDP Glucose Pyrophosphorylase
- Glycogen Synthase (RATE LIMITING)
- Branching Enzyme
Purpose:
- Store glucose as glycogen for fasting state
- Minimize hyperglycemia by decreasing [blood glucose]
Liver:
- Glucose source
- GLUT used
- Sugar trap enzyme
- Amount of glycogen
- Purpose of glycogen
- Glucose source: Portal Vein
- GLUT used: GLUT2 (not insulin reg)
- Sugar trap enzyme: Glucokinase
- Amount of glycogen: 100g
- Purpose of glycogen: Release to bloodstream during fasting/low I/G
Muscle:
- Glucose source
- GLUT used
- Sugar trap enzyme
- Amount of glycogen
- Purpose of glycogen
- Glucose source: Systemic circulation
- GLUT used: GLUT4 (insulin regulated), present in High I/G
- Sugar trap enzyme: hexokinase
- Amount of glycogen: 400g
- Purpose of glycogen: release for MUSCLE’s energy, does not leave muscle cell
Glycogenin
Starts polymerization by accepting glucose from UDP-Glucose
Catalyzes transfer of 4 molecules resulting in short linear chain
Glycogen synthase begins elongating chain by creating alpha 1,4 bonds
Process of Glycogen Synthesis
- Activation of Glucose
- Glucose activated with UDP via UDP-GLUCOSE PHOSPHORYLASE
- G1P–>UDP Glucose - Polymerization of glycogen
- GLYCOGEN SYNTHASE creates alpha 1,4 bonds
- RATE LIMITING STEP - Formation of amylopectin
- BRANCHING ENZYME rearranges 1,4 bonds to form a 1,6 branch point.
Glycogen Synthase & Glycogen Phosphorylase
FED STATE
Phosphorylation State:
-Both enzyme dephosphorylated
Active Enzyme: Glycogen Synthase
Metabolic Effect: Glycogenesis
Glycogen Synthase & Glycogen Phosphorylase
FAST
Phosphorylated state:
-Both enzymes phosphorylated
Active enzyme: Glycogen phosphorylase
Metabolic effect: Glycogenolysis
Effect of Epinephrine on glycogen
overrides effect of insuling
lowers I/G ratio
Increases activation of glycogen phosphorylase
Lipogenesis
-Start subsrate & end product
-enzymes
Purpose
glucose–>triacylglycerol
Enzymes:
- Citrate Lyase
- Acetyl CoA Carboxylase
- Fatty Acid Synthase
Purpose:
- store excess glucose as fatty acids for energy in fast
- supply lipids for membranes
Two stages of Lipogenesis
- de novo fatty acid synthesis
2. synthesis of triacylglycerol
De novo fatty acid synthesis:
Citrate Lyase
Fed state = high glycolysis, high [OAA & Citrate mito]
Excess OAAmito & Citrate mito exported to cytoplasm
Turned back into ACoAcyto & OAAcyto by ATP Citrate Lyase
KEY TAKEAWAY: Citrate activates ATP Citrate Lyase to create ACoA cyto and OAA cyto for FA synthesis
Citrate in De Novo Fatty Acid Synthesis
General: Signal that ATP levels are high
- activates ATP Citrate Lyase (cyto)
- Activates ACC, rate limiting enzyme
- Inhibits PFK-1, rate limiting enzyme in glycolysis
Acetyl-CoA Carboxylase (ACC) Regulation
Acetyl CoA (cyto) –> Malonyl CoA
- Allosteric
- Activator: Citrate stimulates assembly of dimers to active polymer form
- Inhibitor: long-chain fatty acyl-CoA prevents formation of active polymer - Phosphorylation
- Rule of Thumb
- Phosphorylation decreases ACC (low I/G ratio)
- Dephosphorylation increases ACC (high I/G ratio - Protein Synthesis
- high I/G increases ACC synthesis
Fatty Acid Synthase
- Structure
- Function
- Metabolites
Malonyl CoA –> Palmitate
Structure:
- 7 enzymes on one polypeptide
- Biological assembly line: chain becomes increasingly hydrophobic
Function:
- takes 2 C from malonyl CoA at a time to create 16C Palmitate
- NADPH provides needed energy
Metabolites:
-3rd malonyl CoA carbon released as CO2, ensuring reversible and complete reaction
