Ch. 1

albert lehninger studied/found

•Citric acid cycle in mito

•oxidative phosphorylation mech

•Mito struc & func

•Bioenergetics

albert lehninger wrote

classic biochem txtbks

Living organisms conform to

•to all phys & chem laws of behavior of inanimate objects

Macromolecules:

highly ordered polymers that form complex structures in cell

Polymers with a sequence of subunits

generate unique 3D structures for activity

extraction, transform, systematic use of energy

makes, maintains struct, for work

life tries to counteract the universes desire to be

disordered

(tries to reach eq) by envi overall ^disorder

microscopic & large structs are higly

coordinated

w/individual chem compounds

when individual components are interacting w/chem compounds can cause

change in another

whole org display new characteristic

life responds to the changes in envi by

adapting internal chem

can self-rep (precise enough for evolution

invariant cell

cell mem

ribosomes

DNA

RNA

variant cell

mito

chloroplast

nuc membrane

3 domains of life

bacteria

archaea

eukaryote

bacteria cell struct (prokaryote)

ribosomes

cell envelope

pili

nucleoid

flagella

dna

membranes

eukaryote structure

nucleus w/nuc membrane

membrane enclosed organelles

* chloroplasts in plants
* lysosome
* golgi
* mito

eukaryote

spatial separation

of energy making/consuming rxns helps maintain homeotasis

stay away from eq

smooth ER

lipid synthesis

drug metabolism

rough ER

protein synthesis

cytoplasm

v viscous soln where rxns happen

v dense w/proteins

cytoskeleton

cell struct made by protein filaments that cross to make 3D meshwork

* microtubules, actin, intermediate filaments

cytoskeleton funcs

give shape,

org,

transport path,

allow movement

chemotrophs

chemical

auto- CO2

hetero- (organic compounds) all animals, most fungi, protists, bacteria

phototrophs

light

-auto: CO2 (bacteria & plants)

-hetero: organic compounds (bacteria)

cells organization is

dynamic

changes drastically at diff stages

energy from sunlight

plants, some bacteria

energy from fuels

animals, most

biochem studies chem responsible for

* accelling rxns
* org of metabolism & signaling
* store & transfer of info

_ elements essential for life

30

primary elements

C,H,O,N,P,S

metal ions that play role in metabolism

K

Na

Ca

Mg

Zn

Fe

functional groups in biomolecs

derivatives of hydrocarbons with H replaced by a variety of functional groups (i.e. amino acids have amino and carboxyl groups)

building blocks of biochem

sugars (monosacharides)

lipids (FA’s)

AA’s

nucleotides

chirality

chiral carbon w/4 subs

1 chiral = 2 stereoisomers

R and S system

assigned by priority

* decreases in clockwise order, configuration is R (rectus, right)
* Counterclockwise configuration is S (sinister, left)

D and L system

(dextrorotatory and levorotatory):

optical activity, rotation of light (natural amino acids are L-form)

Structural isomers:

same atoms but dif order of bonding,

dif properties

Stereoisomers:

molecs w/same chem bonds but diff configuration, different properties

* enantiomers & diastereomers

Enantiomers

(mirror images):

identical phys properties (except w/polarized light)

react identically w/achiral reagents, may have diff biological activity

Diastereomers

(not mirror images)

geometric isomers (cis/trans)

* have dif phys and chem properties

Isomerases

convert between types (racemase, epimerase, cis-trans isomerase)

molec func depends on

3D struct

Macromolecules have unique

binding pockets, and only certain molecules can fit

binding of chiral biomolecules is

stereospecific

(protein AB, enzymes)

binding specificity ex. glucose

fits into pocket on hexokinase, interacting noncovalently.

* enzyme is specific for D -glucose (in body), not L (not made, except in the lab and by one bacterium)

Olfactory/taste receptors detect

chirality

Drugs can have different

enantiomers/structures, and sometimes different effects

Racemic mixture is

often cheaper than the enantiopure drug, with similar effects

* more common in drugs than pure

Lexapro (Escitalopram) vs. Celexa (Citralopram)

* lexapro: pure, antidepressant SSRI
* celexa: racemic mix of levo isomer (active) & mirror dextro isomer
* need 2x the amt you would bc not pure

In some cases one enantiomer is required

* Citalopram is not recommended for those with heart or liver issues


* L-thyroxine (Synthroid) – thyroid hormone
* D-thyroxine (Choloxin) – lowers cholesterol w/cardiac side effects

1st Law of Thermodynamics:

energy can’t be created or destroyed.

* amt of energy added to break a bond = amt released upon its formation

2nd Law of Thermodynamics

chemical or physical process goes spontaneously in direction of greater disorder (entropy, ΔS)

Cell maintains order at the expense of the

environment

Cells maintain order (-ΔS), which creates

disorder in envi (+ΔS).

**↑S environment > ↓S cell**

The sum of entropy of the system (cell) and surroundings (environment/universe) will be

positive

As metabolic energy is spent to do cellular work, the disorder (randomness) of the system and surroundings (universe)

increases

Organisms return some energy to surroundings as heat and release

end products more disordered than starting fuel

Cells use some energy for anabolic reactions

producing macromolecules: more ordered

* cells ^entropy (+ΔS) of universe

Free energy is the energy

available to do work

Energy change is expressed as change in

ΔG

enthalpy

ΔH (heat)

movement of a system equation

ΔG = ΔH – TΔS

System moves towards

equilibrium concentrations

where ΔG = 0

system energy ex.

NaCl dissolving in solution is favorable -ΔG)

* Heat is absorbed (+ΔH)
* ΔS very positive, thus -TΔS is more negative to offset +ΔH

endothermic rxn

\+ΔG

exothermic rxn

\-ΔG

activation energy during a rxn

prevents rxn from going downhill (as it should) immediately

small activation energies at each step of a rxn cause

energy only to be extracted in a stepwise manner

activation energy ex. glucose

wants to go downhill but doesn’t turn into co2 & h2o right away has to go thru steps

___ lowers activation energy

enzymes

The sum of all free energy changes in a biosynthetic pathway is

significant

Degradative:

^energy bonds made > consumed

a multistep metabolic path is favorable if

overall sum of ∆Gs is negative

∆G tells ___ of reactions as they go toward equilibrium, but not the **speed** of the reaction

direction

Reaction rates increase with:

^er temp

^er conc

lower conc of prods downstream

coupling to fast rxn

lower activation by catalysis

Reaction rates increasing w temp can cause molecs to be

unstable

rxn rates w/^conc of reactants

more costly

Synthesis of complex molecules and many other metabolic reactions requires

energy (endergonic)

endergonic

if -∆G metabolic rxn may have

too high energy barrier

* Metabolite is kinetically stable

Breakdown of some metabolites releases significant amount of energy

exergonic

exergonic metabolites (ATP, NADH, NADPH) can be made from

energy from sun/fuel

* cel conc ^er than eq conc

exergonic rxns

cells continuously make

ATP from ADP +Pi from energy of oxidizing subs (ex.glucose) made by sun

Chemical coupling of exergonic and endergonic rxns lets

unfavorable rxns be able to happen

ATP reacts directly w/metabolite that needs

activation

·       ATP → ADP +  Pi +  Energy

·       Glucose  + Pi → Glucose  6-phosphate

Coupled rxns: (not separate).   

coupled rxns must be done as a grp transfer to

not lose energy

ATP has 2

phosphoanhydride bonds (high energy)

Free energy source that is released in rxns is from

hydrolysis of ATP (**-∆G**)

effects of ATP hydrolysis

·       Consume water

·       Electrostatic repulsion of O relieved

·       ADP > (∆S) than ATP

Grp transfer of ATP is done in coupled rxns so that

energy isn’t released as heat (lost)

ATP grp transfer

Group activation w/AMP or P raises

molec energy state

ATP grp transfer

Enzymes must couple

ATP hydrolysis to other rxns

Catalyst:

compound usually metal that increases rate of chem rxn

Catalyst lower

activation free energy ∆G‡

Catalyst do not change

∆G0

cannot go against equilibrium

Enzymatic catalysis benefits:

·       Accel under mild cond

·       High specify

·       Regulates

·       Couples rxns to atp hydrolysis

·       Avoid side rxns

·       Substrate channeling

enzyme-catalyzed rxns in cells are functionally organized into many sequences of consecutive reactions called

pathways

Metabolic pathways:

make energy or valuable materials

* catabolic or anabolic or amphibolic (both)
* signal transduction pathway transmits info

regulation of pathways changes

conc of enzymes

regulation is more effective in

bacteria > eukaryote bc rapid growth