chemical basis: bonding covalent bonds: sharing of e - –one pair shared = single bondc c –two...

Chemical basis: Bonding

• Covalent Bonds: sharing of e-

– One pair shared = single bond C C– Two pairs = double bond C C– Three pairs = triple bond C C

• Electronegativity (EN) is the ability of an atom to attract electrons to itself– C = 2.5 N = 3.0 O = 3.5 H = 2.1

– Sharing is unequal between different atoms in a molecule• Polar molecules have significant EN differences– H2O, CH3COOH

• Nonpolar molecules have little EN differences– CH3(CH2)nCH3

• Amphipathic molecules have different EN characteristics at different positions– CH3(CH2)nCOOH


• Noncovalent Bonds: attractive forces between atoms of opposite charge– Ionic: fully charged Na+ Cl-

• Strength dependent on environment (salt crystal vs aqueous)

– Hydrogen: partial charge (polar molecules)


• Noncovalent Bonds: continued…– Van der Waals: transient dipole interactions

– Hydrophobic: water fearing– Hydrophilic: water loving

H2O• Can form 4 hydrogen bonds

– High energy barrier to liquid --> gas phase

transition

• Highly polarized– Asymmetric structure - both H atoms on one side

– Can dissolve many compounds

H2O• Can dissolve many compounds

– Acids: can release H+– Bases: can accept H+

pH = - log [H+]• Pure H2O pH = 7 , [H+] = [OH-] = 10-7 M

• Why are reactions so pH sensitive?– Amino acid functional groups can change state based on pH

The importance of water in protein structure

Carbon, Chirality and Stereoisomerism

• Carbon is central to the chemistry of life.– Carbon forms four covalent bonds, with itself or other atoms.

– Carbon-containing molecules produced by living organisms are called biochemicals.

• Chirality and Stereoisomerism:– Asymmetric carbons bond to four different groups.– Molecules with asymmetric carbons can exist in two mirror-image configurations called enantiomers or stereoisomers

– Enantiomers can be either D- or L-isomers

– Natural amino acids are almost all L-isomers– Natural carbohydrates are almost all D-isomers

Stereoisomerism

Classes of molecules• Miscellaneous co-factors

– Vitamins, ATP, NADPH, etc

• Metabolic intermediates– Glycolysis, TCA cycle, etc

• Monomers– Amino acids– rNTPs = rATP, rGTP, rCTP, rUTP– dNTPs = dATP, dGTP, dCTP, dTTP– Sugars

• Macromolecules

Four types of macromolecules

Classes of molecules• Macromolecules

– Lipids• Fats = glycerol esterified with 3 fatty acids– Saturated, unsaturated, cis, trans

• Phospholipids = glycerol + 2 fatty acids + 1 phosphate

• Steroids = cholesterol and derivatives

Monomers and polymers


– Carbohydrates• ( CH2O )n• At n ≥ 5 self-reaction to form rings

– C5 = ribose– C6 = glucose


– “Nutritional” sugars:» Glycogen = branched alpha 1-4 linkage, dense granules in cell cytoplasm in animals

» Starch = helical and branched alpha 1-4 linkage, within membrane bound plastids in plants

alpha 1 --> 4glycogen, starch

beta 1 --> 4cellulose


– “Nutritional” sugars:» Glycogen = branched alpha 1-4 linkage, dense granules in cell cytoplasm in animals

» Starch = helical alpha 1-4 linkage, within membrane bound plastids in plants

plastid


– “Structural” sugars:» Cellulose = long and unbranched, beta 1-4 linkage, resist tensile (pulling) forces, plants

» Chitin = unbranched, N-acetylglucosamine, invertebrates

» Glycosaminoglycans = components of extracellular matrix for cartilage and bone, repeating (A-B)n structure


– Nucleic Acids• Nucleotide monomers (rNTPs, dNTPs)• Storage and transmission of genetic information– Phosphate + 5C ribose sugar + nitrogenous base

RNA DNA

H

• RNA is usually single stranded and DNA is usually double stranded.– RNA may fold back on itself to form complex three dimensional structures, as in ribosomes.

– RNA may have catalytic activity; such RNA enzymes are called ribozymes.

– Adenosine triphosphate (ATP) is a nucleotide that plays a key role in cellular metabolism

– Guanosine triphosphate (GTP) serves as a switch to turn on some proteins.

Classes of molecules


– Proteins• Amino acid monomers• Peptide bond formation• N-terminus versus C-terminus• Backbone is common, side chains (R) differ


– Proteins• Backbone is common, side chains differ

– 4 categories of amino acid side chains» Polar charged D, E, K, R, H» Polar uncharged S, T, Q, N, Y» Nonpolar A, V, L, I, M, F, W» Unique G, C, P

• Post-translational modifications: Phosphorylation


– Proteins• Backbone is common, side chains differ

– 4 categories of amino acid side chains» Polar charged D, E, K, R, H» Polar uncharged S, T, Q, N, Y» Nonpolar A, V, L, I, M, F, W» Unique G, C, P

• Post-translational modifications– Phosphorylation

Hydrophobic and hydrophilic amino acid residues in the

protein cytochrome c


– Proteins• Structure

– Primary» Sequence of the polypeptide chain

H3N-MQWERTYIPASDFGHKLCVN-COOH

H3N-Met Gln Trp Glu Arg Thr Tyr Ile…

Classes of molecules• Secondary

– Alpha-helix (collagen)– Beta-sheet (spider silk)– Side-chain dependence to which form is adopted but stabilization comes from backbone - backbone hydrogen bonding interactions

Classes of molecules• Tertiary

– Side-chain dependent and mediated packing of the secondary elements

– Fibrous proteins = elongated, often structural roles

– Globular = compact, often enzymes– Domains– Conformational changes

Protein structure

• Protein Domains– Domains occur when proteins are composed of two or more distinct regions.

– Each domain is a functional region

Protein structure

• Dynamic Changes within Proteins– May occur with protein activity.

– Conformational changes are non-random movements triggered by various events (e.g. binding, chemical mods…)

Classes of molecules• Quaternary

– Interactions between 2 or more distinct polypeptide chains

Protein Structure

• Protein-Protein Interactions– Results from large-scale studies can be presented in the form of a network.

– A list of potential interactions can be elucidate unknown processes.

Sickle cell anemia

E --> V mutationin hemoglobin

Disease


– Proteins• Protein folding

– Anfinsen RNase A experiment» Denature (unfold) protein in urea and observe loss of activity

» Dialyze the urea away and observe refolding and regain of activity

Demonstrated structure info is inherent to protein sequence

Fold to the lowest energy state Follow a folding pathway

Two alternate pathways for protein folding



– Molecular Chaperones» HSP70 during translation of nascent peptide

» Chaperonins assist post-translation

GroEL-GroES-assisted folding of a polypeptide



– CJD (Mad Cow) & Alzheimers Disease» PrPC --> PrPSc --> plaque» APP --> Ab42 --> plaque

chemical basis: bonding covalent bonds: sharing of e - –one pair shared = single bondc c –two...

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