lecture 14. metabolism biochem = series of coordinated reactions reaction kinetics = thermodynamics,...
TRANSCRIPT
Lecture 14
Metabolism
Biochem = Series of coordinated reactionsReaction kinetics = Thermodynamics, enzyme kineticsGeneral principles of metabolic regulationGlycolysis – reactions, energy
Key regulatory points of Glycolysis
Key regulatory points of Glycolysis
Key regulatory points of Glycolysis
“Signaling” to regulate metabolism
Low Gluose- Where?- Brain response?- Liver response?
How to coordinate? Differential responses?
Roles of different organs in metabolism
library.med.utah.edu
Master regulator
www2.univet.hu
Hormonal control
www.myfitnessstudio.co.uk
Some regulation
Some regulation
Selfish!
Roles of different organs in metabolism
www.udel.edu
science.nationalgeographic.com
“Signaling” to Glycolysis
Example 1: Pyruvate kinase
Low blood sugar = ? Glycolysis (in liver)Low blood sugar = Secrete ?
? (in liver) = Phosphorylate PKPK-PO4 = ? activity
What about in brain?
“Signaling” to Glycolysis
Example 1: Pyruvate kinase
High blood sugar = ? Glycolysis (in liver)High blood sugar = Secrete ?
? (in liver) = ? PK
PK = ? activity
What about in brain?
“Signaling” in Glycolysis
Example 1: Pyruvate kinase
Tissue-specific responses
Example 1: Pyruvate kinase
High blood sugarHormone
PK PK
Liver
Brain
glycolysis
effect
Low blood sugar
Hormone
PK PK
Liver
Brain
glycolysis
effect
Fru 2,6-bis-PO4 regulates Glycolysis
Fru 2,6-bis-PO4 regulates Glycolysis
“Signaling” to Glycolysis
Example 2: Phosphofructokinase 2
PFK2: Fru 6-PO4 Fru 2,6 bis-PO4
Fructose bisphosphatase 2 = reverse
Fru 6-PO4
Fru 2,6 bis-PO4
PFK2 = Fructose bisphosphatase 2 (FBPase2)!
“Signaling” to Glycolysis
Example 2: Phosphofructokinase 2
Huh? Say what?
PFK2 = FBPase2?
What determines which activity is active?
“Signaling” to Glycolysis – Second messengers
Example 2: Phosphofructokinase 2
Remember Glucagon?
Adenylate cyclase = cyclic AMP (cAMP)cAMP activates Protein Kinase A
cAMP is a “second messenger”
(In liver) Glucagon activates “Adenylate cyclase”
Phosphorylation – again!
Example 2: Phosphofructokinase 2
Protein Kinase A (PKA) phosphorylates PFK2
PFK2
FBPase2PO
4
Active FBPase2 = ? Glycolysis
Example 2: Phosphofructokinase 2
Signaling cascade recap
LIVERExample 2: Phosphofructokinase 2
Pancreas
Low Glc
?? Fru 2,6 bis-PO4
Adenylate cyclase↑? PKA?
? PFK1
? GLYCOLYSIS
Signaling cascades
IMPORTANT means of regulationAcross cells
Within cells (Nucleus Mitochondria)Concept of “second messengers”
Role of ATP in cells
Role of ATP in cells