Metabolism

the biochemical reactions that occur within a living organism and the energy exchanges and transformations that accompany them

Catabolism -

Anabolism -

Trophic Strategies -

Autotrophs - synthesize cellular constituents from simple molecules

Heterotrophs - obtain free energy from the oxidation of organic compounds are are ultimately dependent on autotrophs

Nutritional Requirements

Nutritional Requirements

Nutritional Requirements

Building or breaking down a wide range of molecules through conversion to common intermediates

5 Common Characteristics of Metabolic Pathways

1. Metabolic Pathways are Irreversible

2. Every Pathway has a First Committed Step

3. Catabolic and Anabolic Pathways Differ

4. All Metabolic Pathways are Regulated

5. Pathways Occur in Specific Locations

Thermodynamics and Enzymes - Again

First Two Laws of Thermodynamics1. Energy can not be created or destroyed but it may

change forms The energy in the universe remains constant

2. In all natural processes, the entropy of the universe increases

"First: "You can't win.”

Second: "You can't break even.”

Third: "You can't quit the game.”

AP Snow

Thermodynamics and Enzymes - Again

Gibbs Free Energy (G) Amount of energy capable of doing work

*remember - G indicates that the reaction can occur without the input of energy. It DOES NOT indicate that the reaction will occur at a measureable rate.

G is a state function.

Thermodynamics and Enzymes - Again

Gibbs Free Energy (G) Can be calculated from equilibrium concentrations

dependent on both substrate and product concentrations(gas entropy example)

G = G0’ + RTln [C]c[D]d

[A]a[B]b

G = G0’ + RTlnKeq

At equilbrium G = 0 G0’ = -RTlnKeq

Keq = e G0-/RT

G0’ - standard state

R - gas constant

T - temperature

Thermodynamics and Enzymes - Again

Enzymes

1. Alter the rate of a reaction

2. Lower the transition state for the forward and reverse reactions

3. Only function in a reaction that would occur without itSpontaneous reactions (negative G)

4. Are unchanged

Thermodynamics and Metabolism

Near equilibrium reactions - G is close to zero

Far from equilibrium reactions - very large negative G

Thermodynamics and Metabolism

Flux of reactions or rate of flow

Near equilibrium -

Far from equilibrium -

Implications of far from equilibrium1. Metabolic pathways are irreversible2. Every metabolic pathway has a first committed step3. Catabolic and anabolic pathways differ.

Control of Flux

J = Vf-Vr

(flux is equal to the rate of the forward rxn minus the rate of the reverse)

For the pathway as a whole the flux is determined by the rate limiting step

Mechanisms to Control of Flux

1. Allosteric control

2. Covalent modifications

3. Substrate Cycles

4. Genetic Control

5. Metabolic Pathways Occur in Specific Cellular Locations

In multicellular organisms, tissue specific reactions also occur

Enzymes Catalyze Metabolic Reactions

4 major types of reactions1. Oxidations and reductions - oxidoreductases2. Group transfer reactions - transferases and hydrolases3. Eliminations, isomerizations and rearrangements - isomerases and mutases4. Making or breaking Carbon bonds - hydrolases, lyases and ligases

Models of C—H bond breaking.

Models of C—H bond breaking.

Group Transfer Reactions

Transfer of an electrophilic group from one nucleophile

to another. Y: + A - X Y - A + X:

Acyl Group Transferschymotrypsin

Phosphoryl Group Transfershexokinase

Glycosyl Group Transferslysozyme

High Energy Compounds - Free Energy Currency

1. ATP and phosphoryl group transfer

Different ways the cells utilize the high energy bonds in ATP

Coupling endergonic and exergonic reactions• Phosphate group transfers

Inorganic pyrophosphatase (ATP yields AMP + PPi)

NTPs are freely interconverted

ATP + NDP ADP + NTP

Nucleoside diphosphate kinase

Different ways the cells utilize the high energy bonds in ATP

ATP binding and hydrolysis alters conformationGlycogen phosphorylase -

(active)

Other phosphorylated compounds and regeneration of ATP

Substrate level phosphorylation

Oxidative phosphorylation

Oxidation - Reduction ReactionsInvolve the loss or gain of electrons

most biochemical involve C-H bond cleavage with loss of two bonding electrons by carbonusually transferred to electron acceptor (carrier)

NAD+, FADH+

Oxidation - Reduction ReactionsInvolve the loss or gain of electrons

reduction potential - how strongly a compound attractselectrons (larger value, stronger attraction)

Eliminations, Isomerizations and Rearrangements1. Eliminations - formation of a double bond between

two saturated single-bonded centers

Ex. Enolase, fumerase

2. Isomerizations - change in location of double bondintramolecular shift of hydrogen atom

Ex. Phosphoglucose isomerase

Eliminations, Isomerizations and Rearrangements

3. Rearrangements break and reform C-C bonds in a way that

rearranges the carbon skeleton few

Ex. Methylmalonyl CoA mutase (oxidation of odd chain fatty acids)

Reactions that make and breakCarbon Bonds

Many different mechanismsfor you organic fans these include aldol condesations,

(aldolase in glycolysis), Claisen condensations (citrate synthase in TCA cycle), and decarboxylations

We will look at specific mechanisms as we study the pathways

AVG = 161 203St dev = 25 38High = 196, low = 60 276, 134

90% and above (min 450 total course pts) = A 86 - 89 (min 430 pts) = A- 78 - 85 (min 390 pts) = B+ 74 - 77 (min 370 pts) = B 68-73 (min 340 pts) = B- 62 - 67 (min 310 pts) = C+

GradA = > 850 ptsA- = >775 ptsB+ = > 725 ptsB = > 650 ptsB- = > 550 ptsC+ = > 500 pts