Metabolism Flashcards
GLUT 2
- low affinity transporter (Km = 15mM)
- captures excess glucose in 1st order kinetics
- appears in hepatocytes and pancreatic cells (signals insulin release with glucokinase)
GLUT 4
- high affinity transporter (Km = 5mM)
- appears in muscle & adipose tissue (more recruited in presence of insulin)
- muscles turn glucose to glycogen, adipose turns it into DHAP -> G3P -> triacylglycerol
Hexokinase/Glucokinase
Hexokinase - all tissue, low Km, inhibited by G6-P
Glucokinase - hepatocytes/beta islet, high Km, induced by insulin (liver)
- both are irreversible
PFK-1/PFK-2
PFK-1: Fru 6-P -> Fru 1,6-BP
- inhibited by ATP/citrate, activated by AMP
- irreversible
PFK-2: Fru 6-P -> Fru 2,6-BP
- activated by insulin, inhibited by glucagon
- activates PFK-1 to override PFK-1 ATP inhibition
GAP Dehydrogenase
GAP + NAD + Pi -> 1,3-BPG + NADH
3-PG Kinase
1,3-BPG + ADP -> 3-PG + ATP (payoff)
Pyruvate Kinase
PEP + ADP -> pyruvate + ATP
- irreversible
- activated by Fru 1,6-BP
Fermentation
Used to regenerate NAD+ when ETC unavailable
- mammals: pyruvate -> lactate (lactate dehydrogenase)
- yeast: pyruvate -> ethanol + CO2
Galactose Mechanism
Gal -> Gal 1-P by Galactokinase
Gal 1-P -> Glu 1-P by Uridyltransferase + Epimerase
Fructose Mechanism
Fru -> Fru 1-P by Fructokinase
Fru 1-P -> DHAP + Glyceraldehyde by Aldolase B
Pyruvate Dehydrogenase Complex
(1) Pyruvate Dehydrogenase - oxidation to release CO2, needs TPP (vit B1)
(2) Dihydrolipoyl Transacetylase - oxidation of 2C, transfer to lipoic acid, then transfer to acetyl-CoA
(3) Dihydrolipoyl Dehydrogenase - lipoic acid oxidized by FAD -> FADH2, then NAD+ -> NADH
Possible Fates of Pyruvate
Lactate, Acetyl-CoA, Oxaloacetate
Glycogenesis Enzymes
Glycogen Synthase: rate-limiting, forms alpha 1,4 bond
- stimulated by G6-P/insulin, inhibited by epi/glucagon
Branching Enzyme
G-6P becomes G-1P by mutsage then becomes UDP-Glucose before Glycogen Synthase
Glycogenolysis Enzymes
Glycogen Phosphorylase: rate-limiting, breaks alpha 1,4 bond
- activated by glucagon (liver), AMP/epi (muscle)
- inhibited by ATP
Debranching Enzyme - cannot move whole branch so leftover part becomes free glucose
Gluconeogenesis Substrates
G-3P from stored triacylglycerol
Lactate & Glucogenic AA
Propionyl CoA from odd-chain FA
Gluconeogenesis Promotion/Inhibition
Gluconeogenesis is promoted by glucagon/epi and inhibited by insulin
- also requires ATP in liver via B-oxidation
- acetyl-CoA that inhibits PDH complex comes from B-oxidation
4 Accessory Enzymes of Gluconeogenesis
- lactate dehydrogenase (to pyruvate)
- alanine amnotransferase (to pyruvate)
- G-3P dehydrogenase (to DHAP)
- pyruvate carboxylase (mito. pyruvate to OAA to malate, which can go to cytoplasm using malate-asp shuttle)
3 Bypasses of Gluconeogenesis
Phosphoenolpyruvate Carboxykinase (PEPCK)
- located in cytoplasm, OAA -> PEP with GTP
- induced by glucagon and cortisol
Fructose-1,6-Bisphophatase
- located in cytoplasm, rate-limiting, reverse of PFK-1
- activated by ATP, inhibited by AMP & Fru 2,6-BP
Glucose-6-Phosphatase - only in liver ER, NOT muscle
Insulin stimulates
Glycolysis, Glycogenesis, Aerobic Respiration, FA Synthesis, Pentose Phosphate Pathway
Pentose Phosphate Pathway Overall
- occurs in cytoplasm of all cells
- turns G6-P into Ribulose 5-P (creates 2 NADPH) using Glucose-6-P Dehydrogenase (stim by insulin)
- Ribulose 5-P can become Ribose 5-P (for nucleotides)
- RIbose 5-P can become Fru 6-P or GAP by Transketolase (TPP)/Transaldolase
NADPH Functions
- electron donor for FA/cholesterol synthesis
- cellular bleach production
- maintenance of reduced glutathione (radical removal)
Non-PDH Ways to Make Acetyl-Coa
- B-Oxidation: cytosol activation: Fa-CoA using ATP energy, carnitine transport from cytosol then reformation in mitochondria
- AA -> ketone bodies -> acetyl-Coa
- ethanol using alcohol/aldehyde dehydrogenase
Citrate Synthase
OAA ->
