Lecture 14 ATP and High Energy Compounds, Electron Carriers

Metabolism

chemical reactions that occur in cells and organisms that are required for life

Metabolism 3 Characteristics

1)composed of many interconnecting reactions and paths

2) consist of energy producing and energy consuming reactions

3) can drive thermodynamically unfavorable reaction

3 Different Types of Pathways

1) Converging Catabolism

2) Cyclic Pathway (energy production, biosynthetic intermediates)

3) Diverging Anabolism (structural complexity)

Gibbs Free Energy

the energy of a reaction that is available (free) to do work

Exothermic

gibbs free energy is below 0, free energy is released by reaction, favorable

Endothermic

gibss free energy is above 0, energy required for reaction to proceed, unfavorable

Equilibrium

gibbs free energy approaches 0 as the reaction moves to equilibrium

Gibbs Free Energy Prediction

predicts whether a reaction will proceed spontaneously or not, doesn’t tell how long a reaction will take to complete

Change in Enthalpy (H)

changes in the kinds and numbers of chemical bonds, interactions broken and formed during reaction (changes heat content)

Change in Entropy

change in randomness, increase in entropy is increase in disorder, creating order form disorder takes energy and increases delta G

Metabolic Flux

influenced by concentration of substrates and products, high levels of substrate pushed rxn to the right to make products, competition for enzyme

Coupling Reactions

to carry out endergonic reactions (energetically unfavorable), cells couple them to exergonic reactions so overall process is exergonic (energetically favorable)

High Energy Bonds

the free energy due to hydrolysis is more negative (exergonic) than around -6 kcal/mol

Examples of High Energy Bonds

1) Acetyl-CoA

2) phosphoenolpyruvate

3) 1,3-bisphosphoglycerate

4) phosphocreatine

5) XDP to XMP and Pi

6) XTP to XMP and Pi

7) XTP to XMP and Pi

UTP

used for adding sugars

CTP

used for lipid synthesis

GTP

used for protein synthesis

ATP High Energy Bonds

high energy phosphate bonds between phosphate groups

2 High Energy Bonds in Glycolysis

1) 1,3-biphosphoglycerate, phosphate bond

2) phosphoenolpyruvate, phosphate bond

High Energy Bond in Muscle

creatine phosphate, phosphate bond

ATP 3 Made From and Used For

1) made from higher energy phosphates

2) used as a phosphoryl group donor

3) used to drive unfavorable reactions

ATP 3 Functions

1) fuel enzymatic reactions

2) transport of molecules

3) mechanical work

ATP molecules Consumption

within 60s of their generation

ATP Regeneration

continually regenerated by oxidation of C in fuel molecules like glucose, fats, and proteins

3 Energy Producers

carbohydrates, lipid, and protein

5 Energy Utilizations

1) muscle contraction

2) active ion transport

3) biosynthesis

4) detoxification

5) thermogenesis

3 Factors Contributing to High Phosphoryl Group-Transfer Potential of ATP, 3 Steps of ATP Hydrolysis

1) electrostatic repulsion of negatively charged phosphate groups

2) resonance stabilization of ADP and Pi

3) stabilization of ADP and Pi due to hydration

Electrostatic Repulsion

at pH 7 ATP carries 4 negative charges between phosphoanhydride bonds, ADP has 3 and repulsion is reduced upon hydrolysis

Phosphonhydride Bonds and Mg2+

Mg2+ coordination makes phosphotus more electrophilic (attracting electrons)

Resonance Stabilization

orthophospate Pi has 4 resonance forms, -7.3 kcal/mol, SS

Stabilization due to Hydration

water can bind more effectively to ADP and Pi than it can to the phosphoanhydride portion of ATP

Why doesn’t ATP just break down on its own all the time?

ATP can release a lot of energy when hydrolyzed -30.5 kJ/mol very favorable but there’s a high activation energy barrier, needs a push, ATP kinetically stable

ATPases

lower activation energy and help ATP hydrolysis happen only when needed

ATP Function in Which 4 Processes

1) building molecules

2) transport substances

3) muscle movement

4) electrical signaling

Hydrogen Nucleophile Formation in ATP Hydrolysis

H2O is deprotanized by Glu or another H2O and becomes a nucleophile OH- to attack ATP

Attack on Upsilon Phosphate ATP by OH-

OH- attack y-phosphate of ATP which breaks it to ADP and Pi

Arginine Finger

on the arginine side chain from ATPase stabilizes negative charges and polarizes the y-phosphate (makes it easier to attack), holds ATP in position

Mg2+ in ATP hydrolysis

holds the phosphate in place, reduces negative charge repulsion, makes the y-phosphate more electrophilic (easier to attack)

Binding of ligand ATP to Enzyme, 3 Steps

1) ATP to enzyme induces conformational change to close around ligand

2) AA side chains interact with ligand, protein activity can start like DNA binding

3) Mg 2+ interacts with phosphate to neutralize negative charge

4) after hydrolysis the enzyme pocket opens and releases ADP, sometimes the gamma phosphate is transferred to another molecule (kinase activity)

Why don’t we store all our energy as ATP?

many reactions are allosterically inhibited or activated by ATP, especially those that generate energy so ATP is not a good choice to store in large amounts

How Do Muscle Cells Store Energy?

store high energy phosphate bonds in the form of creatine phosphate

Phosphocreatine

in muscle cells, replenishes ATP when ATP is used, very fast so bridges gap between ATP hydrolysis and new ATP made from metabolism, Creatine phosphate and ADP to Creatine and ATP, -3kcal/mol energetically favorable

Thioester and Ester

thioester more reactive than ester, stronger C-O overlap in ester than in thioester (C-S)

Example of Thioester Bonds

between C and S double bonds, acetyl-CoA

Why are Thioester Bonds higher than ordinary Esters?

larger atomic size of S reduced electron overlap between C and S so partial C=S structure doesn’t contribute significantly to resonance stabilization, oxygen ester has 2 resonance forms

Thioester Stability

unstable relative to ester, so it releases more energy to hydrolysis

Adenylylation and Thioester

1) ATP attacked by FA using fatty-acyl-CoA synthetase

2) creates fatty-acyl adenylate (enzyme bounds) an pyrophosphate

3a) pyrophosphate and inorganic pyrophospatase to 2 Pi, -19kJ/mol

3b) fatty acyl adenylate enzyme bound attacked by fatty acyl-CoA synthetase (CoA-SH) release AM) and make fatty acyl-CoA, -15kJ/mol

Pantothenate

vitamin B5, component of CoA (or CoASH) and cofactor for FA synthesis, has SH reactive group

Pantothenate Kinase Deficiency

enzyme needed to charge and activate Vitamin B5 to be incorporated to CoA results in neurological problems

Oxidation

least energy, more O bonds, no more oxygen can be added so e- poor, 0 kJ mol

ex) CO2

Reduction

adding H+ proton and e-, no more H+ can be added (e- rich), reduced most energy

ex) methane -820 kJ mol

2 Main Types of Cellular Fuels

1) glucose, glycolysis, more oxidized

2) fatty acid, beta oxidation, less oxidized

Energy and Proteins

only 10-15% energy derived from protein catabolism

4 Ways to Tranfer e- from Donor to Acceptor

1) direct transfer of e-

2) as H atoms

3) e- transfer as hydride ion

4) direct combination with O2

Direct Transfer of E-

Fe 2+/ Fe 3+ pair transfers e- to Cu+/Cu2+ pair

E- Transfer as H Atoms

AH2 + B= A + BH2 like FAD to FADH2

E- Transfer as Hydride

H- has 2e-, occurs in the case of NAD-linked dehydrogenases

Direct Combination with O2

oxidation of hydrocarbon to alcohol, R-CH3 (e-donor) and O2 (e- acceptor) to RCH2-OH

Most ATP made through?

oxidative phosphorylation

Oxidate Phosphorylation

1) transfer e- from substrates to NAD+ and FAD

2) mitochondrial ETC

3) transfer of e- to oxygen

Absence of Oxygen

energy from oxidation of fuels (NADH and FADH2) can’t be transferred to O2, most ATP production stops

Anaerobic Glycolysis

no oxygen, produces 2 ATP in comparison to the oxidation of glucose through oxidative phosphorylation (30-32 ATP)

Nicotinamide Adenine Dinucleotide

NAD+ (2e-), oxidation of alcohols and aldehydes in which 2 e- removed as H- ion and added to NAD+ forming NADH

Flavin Adenine Dinucleotide

FAD (2H+ and 2e-), oxidation in which electrons (H) removed from separated atoms (double bonds)

Oxidation Reduction Reactions

loss of e- (oxidized) and gain of e- (reduced)

Pellagra

caused by chronic lack of Niacin (vit B3), rash, diarrhea, may be causes by lack of tryptophan (precursor to niacin), related to Hartnup’s (defect in tryptophan absorption), and Crohn’s (insufficient absorption)