Advanced concepts of energy transformation in metabolism biochemistry
Basic Concepts of Metabolism Chapter 15, Stryer Short Course.
-
Upload
laurel-miranda-glenn -
Category
Documents
-
view
223 -
download
0
Transcript of Basic Concepts of Metabolism Chapter 15, Stryer Short Course.
![Page 1: Basic Concepts of Metabolism Chapter 15, Stryer Short Course.](https://reader036.fdocuments.us/reader036/viewer/2022062309/5697bf931a28abf838c8fc17/html5/thumbnails/1.jpg)
Basic Concepts of Metabolism
Chapter 15, Stryer Short Course
![Page 2: Basic Concepts of Metabolism Chapter 15, Stryer Short Course.](https://reader036.fdocuments.us/reader036/viewer/2022062309/5697bf931a28abf838c8fc17/html5/thumbnails/2.jpg)
Stages of Catabolism
• Digestion• Formation of key
intermediate small molecules
• Formation of ATP
![Page 3: Basic Concepts of Metabolism Chapter 15, Stryer Short Course.](https://reader036.fdocuments.us/reader036/viewer/2022062309/5697bf931a28abf838c8fc17/html5/thumbnails/3.jpg)
Key intermediates
![Page 4: Basic Concepts of Metabolism Chapter 15, Stryer Short Course.](https://reader036.fdocuments.us/reader036/viewer/2022062309/5697bf931a28abf838c8fc17/html5/thumbnails/4.jpg)
Fundamental Needs for Energy
• Three needs– Movement– Active transport of
molecules and ions– Biosynthesis
• Complex, but understood in terms of key principles
![Page 5: Basic Concepts of Metabolism Chapter 15, Stryer Short Course.](https://reader036.fdocuments.us/reader036/viewer/2022062309/5697bf931a28abf838c8fc17/html5/thumbnails/5.jpg)
Metabolism
• Interlocking reactions in a pathway
• Catabolism • Anabolism
![Page 6: Basic Concepts of Metabolism Chapter 15, Stryer Short Course.](https://reader036.fdocuments.us/reader036/viewer/2022062309/5697bf931a28abf838c8fc17/html5/thumbnails/6.jpg)
Energetics of Metabolic Pathways
• Unfavorable reactions can be driven by – 1. Coupling to
subsequent spontaneous reaction
– 2. Energy input (change reaction)
Reactant A Product B
Reactant B Product C
Reactant A Product B Reactant A
Product B
Reactant C
Product D
Case 1
Case 2
![Page 7: Basic Concepts of Metabolism Chapter 15, Stryer Short Course.](https://reader036.fdocuments.us/reader036/viewer/2022062309/5697bf931a28abf838c8fc17/html5/thumbnails/7.jpg)
Case 1: Conceptual Understanding• Basically, this is LeChatlier’s Principle• Control of flux—change concentrations
![Page 8: Basic Concepts of Metabolism Chapter 15, Stryer Short Course.](https://reader036.fdocuments.us/reader036/viewer/2022062309/5697bf931a28abf838c8fc17/html5/thumbnails/8.jpg)
Common Motif: Link to pyrophosphate
• The standard free energy of formation of UDP-glucose from G-1-P and UTP is about zero. Yet the production of UDP-glucose is highly favorable. Explain.
Glucose-1-phosphate + UTP UDP-glucose + PPi
![Page 9: Basic Concepts of Metabolism Chapter 15, Stryer Short Course.](https://reader036.fdocuments.us/reader036/viewer/2022062309/5697bf931a28abf838c8fc17/html5/thumbnails/9.jpg)
Case 1: Quantitative Understanding
(Problem 30) The enzyme aldolase catalyzes the reaction below, with a standard free energy of +23.8 kJ/mol. The free energy of the reaction under cellular conditions is -1.3 kJ/mol. Calculate the ratio of reactants to products under equilibrium and cellular conditions. Explain how the reaction can be endergonic under standard conditions, but exergonic under cellular conditions.
![Page 10: Basic Concepts of Metabolism Chapter 15, Stryer Short Course.](https://reader036.fdocuments.us/reader036/viewer/2022062309/5697bf931a28abf838c8fc17/html5/thumbnails/10.jpg)
Problem 14
The formation of acetyl CoA from acetate is an ATP-driven process:
Acetate + ATP + CoA acetyl CoA + AMP + PPi
If the standard free energy of ATP hydrolysis to AMP is -45.6 kJ/mol, and hydrolysis of acetylCoA is -31.4 kJ/mol, what is the standard free energy for this reaction? This reaction is coupled to the hydrolysis of Ppi, with a standard free energy of -19.3 kJ/mol. What is the standard free energy of the coupled reaction? How does the fact that pyrophosphate is constantly hydrolyzed in the cell affect the energetics of formation of acetyl CoA?
![Page 11: Basic Concepts of Metabolism Chapter 15, Stryer Short Course.](https://reader036.fdocuments.us/reader036/viewer/2022062309/5697bf931a28abf838c8fc17/html5/thumbnails/11.jpg)
Case 2: ATP in Metabolism• Overcoming a barrier...– Can’t change concentrations (ammonia is toxic!)
– Change the whole reaction by directly coupling it to a spontaneous reaction: ATP hydrolysis
– Chemical coupling through an enzyme
![Page 12: Basic Concepts of Metabolism Chapter 15, Stryer Short Course.](https://reader036.fdocuments.us/reader036/viewer/2022062309/5697bf931a28abf838c8fc17/html5/thumbnails/12.jpg)
Mechanism of Coupling
![Page 13: Basic Concepts of Metabolism Chapter 15, Stryer Short Course.](https://reader036.fdocuments.us/reader036/viewer/2022062309/5697bf931a28abf838c8fc17/html5/thumbnails/13.jpg)
Quantitative
• Why is this reaction spontaneous?ATP + Glutamate + ammonia ADP + Pi + glutamine
DGo’ = _______• This reaction is a formal combination of these
two reactions:Glutamate + ammonia glutamine DGo’ = +14 kJ/mol ATP ADP + Pi DGo’ = -31 kJ/mol
![Page 14: Basic Concepts of Metabolism Chapter 15, Stryer Short Course.](https://reader036.fdocuments.us/reader036/viewer/2022062309/5697bf931a28abf838c8fc17/html5/thumbnails/14.jpg)
ATP: Chemical Potential
• High energy bonds– Charge repulsion– Resonance– Entropy– Hydration– (acid/base equilibrium)
![Page 15: Basic Concepts of Metabolism Chapter 15, Stryer Short Course.](https://reader036.fdocuments.us/reader036/viewer/2022062309/5697bf931a28abf838c8fc17/html5/thumbnails/15.jpg)
Phosphoryl Transfer in Energetic Intermediates
Phosphoryl group transfer potential
![Page 16: Basic Concepts of Metabolism Chapter 15, Stryer Short Course.](https://reader036.fdocuments.us/reader036/viewer/2022062309/5697bf931a28abf838c8fc17/html5/thumbnails/16.jpg)
Reactions using formal hydrolysis
• Calculate the biological standard free energy for the isomerization of G-1-P to G-6-P. Is it spontaneous under standard conditions? Is it spontaneous when [G-6-P] is 5 mM and [G-1-P] = 0.1 mM?
![Page 17: Basic Concepts of Metabolism Chapter 15, Stryer Short Course.](https://reader036.fdocuments.us/reader036/viewer/2022062309/5697bf931a28abf838c8fc17/html5/thumbnails/17.jpg)
(a) glucose + Pi glucose-6-phosphate + H2O DGo’ = + 13.8 kJ/mol glucose-1-phosphate + H2O glucose + Pi DGo’ = - 20.9 kJ/mol
glucose-1-phosphate glucose-6-phosphate DGo’ = - 7.1 kJ/mol
The reaction is spontaneous under standard conditions.
(b) DG = DGo’ + RT ln [G6P]/[G1P] DG = -7.1 kJ/mol + 8.314 x 10-3 (310K) ln (5 x 10-3 / 0.1 x 10-3) DG = + 3.0 kJ/mol
The reaction is not spontaneous under these conditions.
![Page 18: Basic Concepts of Metabolism Chapter 15, Stryer Short Course.](https://reader036.fdocuments.us/reader036/viewer/2022062309/5697bf931a28abf838c8fc17/html5/thumbnails/18.jpg)
ATP: Middle of High Energy Bonds
![Page 19: Basic Concepts of Metabolism Chapter 15, Stryer Short Course.](https://reader036.fdocuments.us/reader036/viewer/2022062309/5697bf931a28abf838c8fc17/html5/thumbnails/19.jpg)
Phosphocreatine
![Page 20: Basic Concepts of Metabolism Chapter 15, Stryer Short Course.](https://reader036.fdocuments.us/reader036/viewer/2022062309/5697bf931a28abf838c8fc17/html5/thumbnails/20.jpg)
Energy Currency
![Page 21: Basic Concepts of Metabolism Chapter 15, Stryer Short Course.](https://reader036.fdocuments.us/reader036/viewer/2022062309/5697bf931a28abf838c8fc17/html5/thumbnails/21.jpg)
Redox Reactions
• Catabolism– Oxidation
• Anabolism– Reduction
![Page 22: Basic Concepts of Metabolism Chapter 15, Stryer Short Course.](https://reader036.fdocuments.us/reader036/viewer/2022062309/5697bf931a28abf838c8fc17/html5/thumbnails/22.jpg)
Capturing Chemical Potential
• Reduced carbons have much potential
• Oxidation releases potential
• Can be coupled to formation of high energy bond
![Page 23: Basic Concepts of Metabolism Chapter 15, Stryer Short Course.](https://reader036.fdocuments.us/reader036/viewer/2022062309/5697bf931a28abf838c8fc17/html5/thumbnails/23.jpg)
Recurring Motif: Activated Carrier
• Capturing chemical potential in activated carriers
• A. NAD+/NADH
![Page 24: Basic Concepts of Metabolism Chapter 15, Stryer Short Course.](https://reader036.fdocuments.us/reader036/viewer/2022062309/5697bf931a28abf838c8fc17/html5/thumbnails/24.jpg)
![Page 25: Basic Concepts of Metabolism Chapter 15, Stryer Short Course.](https://reader036.fdocuments.us/reader036/viewer/2022062309/5697bf931a28abf838c8fc17/html5/thumbnails/25.jpg)
Activated Carriers
• B. FAD/FADH2
• Can transfer one electron or two electrons
• Different redox reactions than NADH
![Page 26: Basic Concepts of Metabolism Chapter 15, Stryer Short Course.](https://reader036.fdocuments.us/reader036/viewer/2022062309/5697bf931a28abf838c8fc17/html5/thumbnails/26.jpg)
![Page 27: Basic Concepts of Metabolism Chapter 15, Stryer Short Course.](https://reader036.fdocuments.us/reader036/viewer/2022062309/5697bf931a28abf838c8fc17/html5/thumbnails/27.jpg)
Catalytic Redox Cofactors
• Electron transport chain• Purpose of breathing oxygen
![Page 28: Basic Concepts of Metabolism Chapter 15, Stryer Short Course.](https://reader036.fdocuments.us/reader036/viewer/2022062309/5697bf931a28abf838c8fc17/html5/thumbnails/28.jpg)
Activated Carriers
• C. NADP+/NADH• For biosynthesis
![Page 29: Basic Concepts of Metabolism Chapter 15, Stryer Short Course.](https://reader036.fdocuments.us/reader036/viewer/2022062309/5697bf931a28abf838c8fc17/html5/thumbnails/29.jpg)
Activated Carriers
• D. Acyl group carriers• Coenzyme A• Thioesters– Unstable resonance
• High energy bonds
![Page 30: Basic Concepts of Metabolism Chapter 15, Stryer Short Course.](https://reader036.fdocuments.us/reader036/viewer/2022062309/5697bf931a28abf838c8fc17/html5/thumbnails/30.jpg)
Activated Carriers
![Page 31: Basic Concepts of Metabolism Chapter 15, Stryer Short Course.](https://reader036.fdocuments.us/reader036/viewer/2022062309/5697bf931a28abf838c8fc17/html5/thumbnails/31.jpg)
B Vitamins
![Page 32: Basic Concepts of Metabolism Chapter 15, Stryer Short Course.](https://reader036.fdocuments.us/reader036/viewer/2022062309/5697bf931a28abf838c8fc17/html5/thumbnails/32.jpg)
Vitamin Chemistry• We will build throughout semester• Introduction to fundamental chemistry of
decarboxylation
Pyridoxyl Phosphate (PLP) Vitamin B6
![Page 33: Basic Concepts of Metabolism Chapter 15, Stryer Short Course.](https://reader036.fdocuments.us/reader036/viewer/2022062309/5697bf931a28abf838c8fc17/html5/thumbnails/33.jpg)
Other Vitamins
![Page 34: Basic Concepts of Metabolism Chapter 15, Stryer Short Course.](https://reader036.fdocuments.us/reader036/viewer/2022062309/5697bf931a28abf838c8fc17/html5/thumbnails/34.jpg)
Thermodynamics vs Kinetics
• Characteristics of an energy currency or activated carrier:
• Kinetically stable• Thermodynamically
unstable
![Page 35: Basic Concepts of Metabolism Chapter 15, Stryer Short Course.](https://reader036.fdocuments.us/reader036/viewer/2022062309/5697bf931a28abf838c8fc17/html5/thumbnails/35.jpg)
Qualitative Predictions
• Inherently favorable, unfavorable, or near equilibrium?
![Page 36: Basic Concepts of Metabolism Chapter 15, Stryer Short Course.](https://reader036.fdocuments.us/reader036/viewer/2022062309/5697bf931a28abf838c8fc17/html5/thumbnails/36.jpg)
Uphill or Downhill?
![Page 37: Basic Concepts of Metabolism Chapter 15, Stryer Short Course.](https://reader036.fdocuments.us/reader036/viewer/2022062309/5697bf931a28abf838c8fc17/html5/thumbnails/37.jpg)
Regulation
![Page 38: Basic Concepts of Metabolism Chapter 15, Stryer Short Course.](https://reader036.fdocuments.us/reader036/viewer/2022062309/5697bf931a28abf838c8fc17/html5/thumbnails/38.jpg)
Regulation
• Control amount of enzyme
• Control activity of enzyme– Energy charge
• Compartmentalization
𝐸𝑛𝑒𝑟𝑔𝑦 h𝑐 𝑎𝑟𝑔𝑒=[ 𝐴𝑇𝑃 ]+
12[𝐴𝐷𝑃 ]
[ 𝐴𝑇𝑃 ]+ [ 𝐴𝐷𝑃 ]+[ 𝐴𝑀𝑃 ]