Lecture 14. Metabolism Biochem = Series of coordinated reactions Reaction kinetics = Thermodynamics, enzyme kinetics General principles of metabolic regulation.

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Presentation transcript:

Lecture 14

Metabolism Biochem = Series of coordinated reactions Reaction kinetics = Thermodynamics, enzyme kinetics General principles of metabolic regulation Glycolysis – reactions, energy

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 Some regulation

Selfish! Roles of different organs in metabolism science.nationalgeographic.com

“Signaling” to Glycolysis Example 1: Pyruvate kinase Low blood sugar = ? Glycolysis (in liver) Low blood sugar = Secrete ? ? (in liver) = Phosphorylate PK PK-PO 4 = ? 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 sugar Hormone PK LiverBrain glycolysiseffect Low blood sugar Hormone PK LiverBrain glycolysiseffect

Fru 2,6-bis-PO 4 regulates Glycolysis

“Signaling” to Glycolysis Example 2: Phosphofructokinase 2 PFK2 : Fru 6-PO4  Fru 2,6 bis-PO4 Fructose bisphosphatase 2 = reverse Fru 6-PO4Fru 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? 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 PFK2FBPase2 PO 4 Active FBPase2 = ? Glycolysis

Example 2: Phosphofructokinase 2

Signaling cascade recap LIVER Example 2: Phosphofructokinase 2 Pancreas Low Glc ? ? Fru 2,6 bis-PO4 Adenylate cyclase ? PKA ? ? PFK1 ? GLYCOLYSIS

Signaling cascades IMPORTANT means of regulation Across cells Within cells (Nucleus  Mitochondria) Concept of “second messengers”

Role of ATP in cells