Download ch2 FA11 - Cal State LA

Chemical basis: Bonding
• Covalent Bonds: sharing of e– One pair shared = single bond
– Two pairs = double bond
– Three pairs = triple bond
C
C
C
C
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
Chemical basis: Bonding
• Noncovalent Bonds: attractive forces between atoms of
opposite charge
– Ionic: fully chargedNa+ Cl• Strength dependent on environment (salt crystal vs aqueous)
– Hydrogen: partial charge (polar molecules)
Chemical basis: Bonding
• 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 mirrorimage 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
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
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
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
Classes of molecules
• Macromolecules
– Carbohydrates
• ( CH2O )n
• At n ≥ 5 self-reaction to form rings
– C5 = ribose
– C6 = glucose
Classes of molecules
• Macromolecules
– “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 --> 4
glycogen, starch
beta 1 --> 4
cellulose
Classes of molecules
• Macromolecules
– “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
Classes of molecules
• Macromolecules
– “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
Classes of molecules
• Macromolecules
– Nucleic Acids
• Nucleotide monomers (rNTPs, dNTPs)
• Storage and transmission of genetic information
– Phosphate + 5C ribose sugar + nitrogenous base
RNA
DNA
H
Classes of molecules
• 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
• Macromolecules
– Proteins
•
•
•
•
Amino acid monomers
Peptide bond formation
N-terminus versus C-terminus
Backbone is common, side chains (R) differ
Classes of molecules
• Macromolecules
– 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
Classes of molecules
• Macromolecules
– 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
Classes of molecules
• Macromolecules
– 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
Classes of molecules
• Macromolecules
– 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
Classes of molecules
• Macromolecules
– 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 nonrandom 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 largescale studies can be
presented in the
form of a network.
– A list of potential
interactions can be
elucidate unknown
processes.
Disease
Sickle cell anemia
E --> V mutation
in hemoglobin
Classes of molecules
• Macromolecules
– 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
Classes of molecules
• Macromolecules
– Proteins
• Protein folding
– Molecular Chaperones
» HSP70 during translation of nascent peptide
» Chaperonins assist post-translation
GroEL-GroES-assisted folding of a polypeptide
Classes of molecules
• Macromolecules
– Proteins
• Protein folding
– CJD (Mad Cow) & Alzheimers Disease
» PrPC --> PrPSc --> plaque
» APP --> Ab42 --> plaque
Classes of molecules
• Macromolecules
– Proteins
• Protein folding
– CJD (Mad Cow) & Alzheimers Disease
» PrPC --> PrPSc --> plaque
» APP --> Ab42 --> plaque