mcat biochemistry

amino acids

-have four groups attached to a central carbon: an amino group (-NH₂), a carboxyl group (-COOH), a hydrogen atom, and an R group -the R group determines chemistry and function

α-amino acids

amino acids in which the amino group and the carboxyl group are bonded to the α-carbon of the carboxylic acid

proteinogenic amino acids

-the 20 α-amino acids encoded by the human genetic code -most are chiral and optically active (except glycine) -all chiral amino acids used in eukaryotes are L-amino acids (except cysteine)

which amino acid is achiral?

glycine

which amino acid has an (R) absolute configuration?

cysteine

amino acid side chains

can be polar or nonpolar, aromatic or nonaromatic, charged or uncharged

nonpolar, nonaromatic amino acids

glycine, alanine, valine, leucine, isoleucine, methionine, proline

aromatic amino acids

tryptophan, phenylalanine, tyrosine

polar amino acids

serine, threonine, asparagine, glutamine, cysteine

negatively charged (acidic) amino acids

aspartate, glutamate

positively charged (basic) amino acids

lysine, arginine, histidine

alanine

Ala, A nonpolar, nonaromatic

arginine

Arg, R positively charged (basic)

asparagine

Asn, N polar

aspartic acid

Asp, D negatively charged (acidic) anion is aspartate

cysteine

Cys, C polar

glutamic acid

Glu, E negatively charged (acidic) anion is glutamate

glutamine

Gln, Q polar

glycine

Gly, G nonpolar, nonaromatic

histidine

His, H positively charged (basic)

isoleucine

Ile, I nonpolar, nonaromatic

leucine

Leu, L nonpolar, nonaromatic

lysine

Lys, K positively charged (basic)

methionine

Met, M nonpolar, nonaromatic

phenylalanine

Phe, F aromatic

proline

Pro, P nonpolar, nonaromatic

serine

Ser, S polar

threonine

Thr, T polar

tryptophan

Trp, W aromatic

tyrosine

Tyr, Y aromatic

valine

Val, V nonpolar, nonaromatic

classifying amino acids as hydrophobic or hydrophilic

-hydrophobic: have long alkyl chains -hydrophilic: are charged

hydrophobic amino acids

alanine, isoleucine, leucine, valine, and phenylalanine

hydrophilic amino acids

histidine, arginine, lysine, glutamate, aspartate, asparagine, glutamine

amphoteric species

-can accept or donate protons -how they react depends on the pH of their environment

pKa

the pH at which half of the species is deprotonated, [HA] = [A⁻]

pKa₁

-the pKa for the carboxyl group -usually around 2

pKa₂

-the pKa for the amino group -usually between 9 and 10

amino acid protonation (pH and pKa)

-if pH < pKa: mostly protonated -if pH > pKa: mostly deprotonated

amino acid protonation (pH)

-at low (acidic) pH: fully protonated -at pH near the pI of the amino acid: neutral zwitterion -at high (alkaline) pH: fully deprotonated

amino acid charge (pH)

-at low (acidic) pH: positively charged -at pH near the pI of the amino acid: as both a positive and a negative charge, but overall is electrically neutral -at high (alkaline) pH: negatively charged

isoelectric point (pI)

the pH at which the molecule is electrically neutral

calculating the pI of amino acids without charged side chains

calculated by averaging the two pKa values

calculating the pI of amino acids with charged side chains

calculated by averaging the two pKa values that correspond to protonation and deprotonation of the zwitterion

isoelectric point of a neutral amino acid

pI = [pKa (NH₃⁺ group) + pKa (COOH group)]/2 ∼6

isoelectric point of a acidic amino acid

pI = [pKa (R group) + pKa (COOH group)]/2 well below 6

isoelectric point of a basic amino acid

pI = [pKa (NH₃⁺ group) + pKa (R group)]/2 well above 6

titration curve of amino acids

-nearly flat at the pKa values of the amino acid -nearly vertical at the pI of the amino acid

peptides and amino acid residues

-dipeptides: have 2 AA residues
-tripeptides: have 3 AA residues
-oligopeptides: have a few AA residues (

peptide bond

-a specialized form of an amide bond that forms between the -COO⁻ group of one amino acid and the NH₃⁺ group of another amino acid -forms the functional group -C(O)NH-

peptide bond formation

-a condensation or dehydration reaction (releases one molecule of water) -the nucleophilic amino group of one amino acid attacks the electrophilic carbonyl group of another amino acid, and the hydroxyl group of the carboxylic acid is kicked off

what type of reaction is the formation of a peptide bond?

condensation or dehydration

resonance in a peptide bond

-amide bonds are rigid because of resonance -because amide groups have delocalizable π electrons in the carbonyl and in the lone pair on the amino nitrogen, they can exhibit resonance -the C-N bond in the amide has partial double bond character, and rotation of the protein backbone around its C-N amide bonds is restricted, which makes the protein more rigid

N-terminus

-aka amino terminus -the free amino end of a peptide

C-terminus

-aka carboxy terminus -the free carboxyl end of a peptide

how are peptides conventionally drawn and read?

-drawn with the N-terminus on the left and the C-terminus on the right -read from N-terminus to C-terminus (left to right)

peptide bond hydrolysis

-catalyzed by hydrolytic enzymes such as trypsin and chymotrypsin, which: •are specific, in that they only cleave at specific points in the peptide chain •break apart the amide bond by adding a hydrogen atom to the amide nitrogen and an OH group to the carbonyl carbon

hydrolytic enzymes

trypsin & chymotrypsin

what type of reaction is the breaking of a peptide bond?

hydrolysis

chymotrypsin

cleaves at the carboxyl end of phenylalanine, tryptophan, and tyrosine (aromatics)

trypsin

cleaves at the carboxyl end of arginine and lysine

proteins

polypeptides that range from just a few amino acids in length up to thousands

four levels of protein structure

-primary: amino acid sequence (peptide bonds) -secondary: amino acid structure (α-helices, β-pleated sheets, hydrogen bonds) -tertiary: 3D shape (hydrophobic interactions, salt bridges, hydrogen bonds, disulfide bonds) -quaternary: interaction between subunits

stabilizing bonds in each level of protein structure

-primary: peptide (amide) -secondary: hydrogen -tertiary: van der Waals, hydrogen, ionic, covalent -quaternary: van der Waals, hydrogen, ionic, covalent

primary structure

-the linear sequence of amino acids in a peptide -stabilized by peptide bonds

secondary structure

-the local structure of neighboring amino acids -stabilized by hydrogen bonding between amino groups and nonadjacent carboxyl groups -key features: α-helices, β-pleated sheets

α-helices

-a rodlike structure in which the peptide chain coils clockwise around a central axis -stabilized by intramolecular hydrogen bonds between a carbonyl oxygen atom and an amide hydrogen atom four residues down the chain -the side chains point away from the helix core

example of a protein with α-helices

keratin (a fibrous structural protein found in human skin, hair, and fingernails)

β-pleated sheets

-a parallel or antiparallel structure in which the peptide chains lie alongside one another, forming rows or strands -held together by intramolecular hydrogen bonds between carbonyl oxygen atoms on one chain and amide hydrogen atoms in an adjacent chain -assume a pleated, or rippled, shape to accommodate as many hydrogen bonds as possible -the R groups point above and below the plane

example of a protein with β-pleated sheets

fibroin (the primary protein component of silk fibers)

proline and secondary protein structure

-can interrupt secondary structure because of its rigid cyclic structure -introduces a kink in the peptide chain when it is found in the middle of an α-helix

tertiary structure

-the three-dimensional shape of a single polypeptide chain -mostly determined by hydrophilic and hydrophobic interactions between R groups of amino acids -stabilized by hydrophobic interactions, acid-base interactions (salt bridges), hydrogen bonding, and disulfide bonds -stabilizing bonds: van der Waals, hydrogen, ionic, covalent

salt bridges

created as a result of acid-base interactions between amino acids with charged R groups

disulfide bonds

-the bonds that form when two cysteine molecules become oxidized to form cystine -create loops in the protein chain and determine how wavy or curly human hair is -formation requires the loss of two protons and two electrons (oxidation)

fibrous proteins

-have structures that resemble sheets or long strands -ex: collagen

globular proteins

-tend to be spherical -ex: myoglobin

protein folding and entropy

-by moving hydrophobic residues away from water molecules and hydrophilic residues toward water molecules, a protein achieves maximum stability -this is an energetically favorable (∆S > 0) and spontaneous (∆G < 0) process

quaternary structure

-the interaction between peptides in proteins that contain multiple subunits -only exist for proteins that contain more than one polypeptide chain -stabilizing bonds: van der Waals, hydrogen, ionic, covalent

roles of the quaternary structure

-can be more stable, by further reducing the surface area of the protein complex -can reduce the amount of DNA needed to encode the protein complex -can bring catalytic sites close together, allowing intermediates from one reaction to be directly shuttled to a second reaction -can induce cooperativity, or allosteric effects

cooperativity

-aka allosteric effects -one protein subunit can undergo conformational or structural changes, which either enhance or reduce the activity of the other subunits

conjugated proteins

proteins with covalently attached molecules

prosthetic group

-molecules that are covalently attached to a conjugated protein -have major roles in determining the function of their respective proteins -ex: metal ion, vitamin, lipid, carbohydrate, nucleic acid

denaturation

-loss of three-dimensional protein structure, caused by heat or increasing solute concentration -causes a loss of protein function

denaturation (heat)

-when the temperature of a protein increases, the average kinetic energy increases -when the temperature gets high enough, the extra energy can be enough to overcome the hydrophobic interactions that hold a protein together, causing the protein to unfold -ex: cooking egg whites

denaturation (solutes)

-solutes denature proteins by directly interfering with the forces that hold the protein together -can disrupt tertiary and quaternary structures by breaking disulfide bridges, reducing cystine back to two cysteine residues -can overcome the hydrogen bonds and other side chain interactions that hold α-helices and β-pleated sheets intact -detergents such as SDS can solubilize proteins, resulting in a hydrophobic core that promotes denaturation of the protein -ex: urea

enzymes

biological catalysts that are unchanged by the reactions they catalyze and are reusable

catalysts

-lower the activation energy necessary for biological reactions -do not alter the free energy (∆G) or enthalpy (∆H) change that accompanies the reaction nor the final equilibrium position; rather, they change the rate (kinetics) at which equilibrium is reached

key features of enzymes

-lower the activation energy -increase the rate of the reaction -do not alter the equilibrium constant -are not changed or consumed in the reaction (appear in both the reactants and products) -are pH- and temperature-sensitive, with optimal activity at specific pH ranges and temperatures

• do not affect the overall ∆G of the reaction -are specific for a particular reaction or class of reactions

enzyme specificity

each enzyme catalyzes a single reaction or type of reaction with high specificity

oxidoreductases

-catalyze oxidation-reduction reactions that involve the transfer of electrons -reductant: the electron donor; ex: dehydrogenase, reductase -oxidant: the electron acceptor; ex: oxidase

Examples of oxidoreductases

dehydrogenase, reductase

transferases

-move a functional group from one molecule to another molecule -ex: aminotransferase, kinases

kinases

catalyze the transfer of a phosphate group, generally from ATP, to another molecule

hydrolases

-catalyze cleavage with the addition of water -ex: phosphatase, peptidases, nucleases, lipases

lyases

-catalyze cleavage without the addition of water and without the transfer of electrons -the reverse reaction (synthesis) is often more important biologically -ex: synthases

isomerases

catalyze the interconversion of isomers, including both constitutional isomers and stereoisomers

ligases

responsible for joining two large biomolecules, often of the same type

mnemonic for major enzyme classifications

LI'L HOT: Ligase, Isomerase, Lyase, Hydrolase, Oxidoreductase, Transferase

endergonic reaction

require energy, ∆G > 0

exergonic reaction

release energy, ∆G < 0