Amino Acids and Protein Structure (Biochemistry)

A set of vocabulary flashcards covering key concepts from amino acids, protein structure, globular/fibrous proteins, enzymes, kinetics, regulation, and disease from the Biochemistry lecture notes.

Amino acids

Building blocks of proteins; 20 standard amino acids encoded by DNA (abundant and functionally diverse)

Standard (common) amino acids

The 20 amino acids commonly found in mammalian proteins, encoded by DNA. (common or standard A.As)

Amino group

The -NH2 group attached to the α-carbon of an amino acid; participates in peptide bond formation.

Carboxyl group

The -COOH group attached to the α-carbon; forms peptide bond with the next amino acid.

α-carbon

The central carbon of an amino acid bearing the amino group, carboxyl group, hydrogen, and the side chain (R).

Side chain (R group)

The variable group that determines an amino acid’s unique properties.

Proline

Amino acid with a secondary amino group that forms a rigid ring; disrupts α-helices and helps form extended fibrous collagen formation. (only secondary amino group most are primary)

Peptide Linkages

How different amino acids are linked together

Structure of Amino Acid at physiologic ph

Carboxyl (-COO) is deprotonated occurs at 2 PH and amino group (nh3+) occurs at 9 Ph

Amphoteric property

At physiological pH, amino acids can act as both acids and bases.

Zwitterion

Amino acids at physiological pH that carry both positive and negative charges but are overall electrically neutral.

Classes of amino acids

Four categories based on side-chain properties: nonpolar, uncharged polar, acidic, and basic.

Nonpolar amino acids

Amino acids with hydrophobic/ side chains and has lipid like properties; tend to be in protein interiors (aqueous solution)or membranes (hydrophobic environment)

Biochemistry of Sickle Cell Anemia

In RBCs from substitution of glutamate to Valine at the 6th position of the 2nd beta subunit of hemoglobin A

Subunit of Hemoglobin

4 subunits 2 Alpha and 2 Beta

Sickle Cell Anemia

in low O2 conditions, valine causes aggregation of hemogolobin leading to a ickled shaped with decreased elasticity. Sickled cells are less efficient at traveling through capillaries leading to vessel occlusion and ischemia

Hemoylsis

The breakdown of RBC occurs much sooner in sickled cells (10-20) rather than 90-120 days in normal RBC. Results in Hemolytic Anemia, too because the destruction rate is faster than the renewal rate in the bone marrow

Uncharged polar amino acids

Amino acids with polar but uncharged side chains (hydropillic and can partake in H-Bonding) (e.g., Ser, Thr, Asn, Gln, Tyr, Cys). Q- Glutamine (2 amine) T-Theronine (Ch3-OH) S-serine (OH-H) C-Cystsine (Sh) N- Aspargine (NH2) Y- Tyrosine (oh-phenyl)

hydroxyl group

serves as attachment site for phosphate group

amide

attachment for oligosaccharcide chains in glycoproteins

sulfhydryl

active sites of enzymes

Acidic amino acids

Aspartate (Asp) and Glutamate (Glu); (proton donors) side chains carry a negative charge at physiological pH. O=C-o- groups

Basic amino acids

Lysine (Lys), Arginine (Arg), Histidine (His); (proton Acceptors) side chains are positively charged at physiological pH (Histidine is partially ionized).

Essential AA

NOT produced by the body No ACG.

Non-Essential AA

A-C-G

Enantiomers

All AAs in mammailian proteins are of L-configuration
-mirror images
-clockwise - R

-counter clockwise- L

glycine as a special case

Glycine is not chiral because it has two hydrogen atoms on the α-carbon.

pKa

Acid dissociation constant; pKa = -log10(Ka); indicates acid strength (lower pKa = stronger acid).

Henderson-Hasselbalch equation

pH = pKa + log([A−]/[HA]); relates pH to acid/base species in buffers.

Buffer

A solution of a weak acid and its conjugate base that resists pH change; AA contains weakly acidic a-carboxyl groups and basic a-amino groups

pH buffer should be within ± 1 pH unit of the acids pKa value

Maximal buffering when weak = conjugate base

Isoelectric point (pI)

pH at which a molecule has no net electric charge; for amino acids with two pKa values, pI lies between them. pKa

Titration of an amino acid

Plot of pH as titrant is added; shows different pKa values and the pI where net charge is zero.

if pH < pKa protonated acid form (HA) predom (COOH or Nh3+)

if pH > pKa depotonated base form (A-) predom (COO- or NH2)

DNA to protein relationship

DNA sequence determines the amino acid sequence of a protein via transcription to RNA and translation.

Primary structure

Linear sequence of amino acids in a protein.

Peptide bond

Amide bond between the carboxyl group of one amino acid and the amino group of the next.

can e hydrozled nonenzymatically by strong acid or base or at high temperature

Peptidases

Enzymes that hydrolyze peptide bonds; include exopeptidases (terminal cuts) and endopeptidases (internal cuts).

aminopeptidases

cuts amino end

carboxypeptidases

cuts carboxyl end

N-terminus and C-terminus

N-terminus is the amino end of a polypeptide; C-terminus is the carboxyl end.

Naming polypeptides

When naming a peptide, residues are given in sequence from N- to C-terminus; terminal amino acids retain their standard suffixes.

Trans vs cis peptide bonds

Peptide bonds are generally trans due to steric hindrance in the cis form.

Amino acid enantiomers (D/L)

Optical isomers; most mammalian proteins use L-amino acids; glycine is not chiral.

Secondary structure

Regular sub-structures formed by hydrogen bonding in the polypeptide backbone (α-helix and β-sheet).

α-helix

Right-handed spiral; 3.6 amino acids per turn; side chains extend outward; proline disrupts the helix.

β-sheet

Sheets formed by hydrogen bonding between backbone C=O and N–H of adjacent strands; can be parallel or antiparallel.

Tertiary structure

Three-dimensional folding of a single polypeptide; stabilized by hydrogen bonds, disulfide bonds, ionic interactions, and hydrophobic effects.

Chaperones

Proteins that assist in proper protein folding.

Denaturation

Unfolding of a protein’s structure; loss of secondary/tertiary structure without peptide bond cleavage; caused by heat, solvents, detergents, etc.

Quaternary structure

3D structure formed by the assembly of multiple polypeptide chains; subunits may be independent or cooperative.

Fibrous vs globular proteins

Fibrous proteins (e.g., collagen, elastin, keratin) are structural; globular proteins (e.g., myoglobin, hemoglobin) are soluble enzymes and transport proteins.

Collagen

Fibrous protein; triple-helix structure; abundant in connective tissue; Type I is most common; glycine every third residue is characteristic.

Hydroxyproline

Post-translationally modified proline; important for collagen stability.

Biosynthesis of collagen

Transcription -> translation -> RER -> procollagen -> Golgi -> secretion -> tropocollagen and cross-linking to form fibrils.

Elastin

Elastin gives connective tissue its rubber-like properties; stretches and recoils; found in lungs and arterial walls.

Keratin

Fibrous protein in hair, nails, and skin; α-helical coiled-coil structure; forms protofilaments and filaments.

Heme

Iron-containing prosthetic group in hemoglobin and myoglobin that binds oxygen.

Myoglobin

Globular hemeprotein in muscle; stores and transports O2; single polypeptide; high O2 affinity.

Hemoglobin

Tetrameric globular protein in red blood cells; transports O2 (and CO2/H+); exhibits cooperative binding.

HbA

Adult hemoglobin: two α and two β subunits with a heme pocket; primary oxygen-carrying form in adults.

Bohr effect

pH changes (H+) shift Hb's O2 affinity; increased acidity lowers affinity, shifting the curve to the right.

2,3-Bisphosphoglycerate (2,3-BPG)

Allosteric effector that reduces Hb’s affinity for O2; higher levels shift the curve to the right (altitude adaptation).

Carbon monoxide and Hb

CO binds heme with very high affinity, stabilizing the R state and preventing O2 release; highly toxic.

Hemoglobinopathies

Genetic disorders of Hb; examples: HbS (Glu→Val), HbC (Glu→Lys), HbSC, and thalassemias.

Globular vs fibrous proteins (recap)

Globular: soluble, functional proteins (e.g., enzymes, Hb, Mb). Fibrous: structural proteins (e.g., collagen, elastin, keratin).

Glycoproteins and glycosylation

Proteins with attached oligosaccharides; N-linked (Asn) and O-linked (Ser/Thr) glycosylation affecting function.

Enzymes

Protein catalysts that increase reaction rates and are not consumed in the reaction.

Cofactors and coenzymes

Nonprotein components required for enzyme activity; cofactors can be inorganic/organic; coenzymes are organic (often vitamin derivatives).

Holoenzyme vs apoenzyme

Holoenzyme is an enzyme with its prosthetic group/cofactor; apoenzyme is the protein part without the nonprotein component.

Prosthetic group and cosubstrate

Prosthetic group: permanently bound nonprotein component; cosubstrate: transiently associated organic component.

Allosteric enzymes

Enzymes regulated by effectors binding at sites other than the active site; can show cooperative (sigmoidal) kinetics.

Michaelis-Menten kinetics

Describes most enzyme-catalyzed reactions with hyperbolic velocity vs substrate; V0 = Vmax[S]/(Km+[S]).

Lineweaver-Burk plot

Double reciprocal plot (1/v0 vs 1/[S]); linear; used to determine Km and Vmax and inhibition type.

Km and Vmax

Km = substrate concentration at half-max velocity; reflects affinity (lower Km = higher affinity). Vmax = maximum velocity when enzyme is saturated.

Enzyme inhibitors

Molecules that decrease enzyme-catalyzed reaction rate; can be reversible (competitive or noncompetitive) or irreversible.

Competitive inhibition

Inhibitor competes with substrate for active site; increases apparent Km; Vmax unchanged.

Noncompetitive inhibition

Inhibitor binds at a site other than the active site; decreases Vmax; Km may be unchanged.

Allosteric regulation

Regulation by effectors at sites other than the active site; can be negative or positive; homogeneous vs heterotropic effects.

Covalent modification of enzymes (phosphorylation)

Regulation by adding/removing phosphate groups (kinases/phosphatases); can activate or inhibit enzyme activity.

Induction and repression of enzyme synthesis

Cells control total enzyme activity by regulating synthesis and degradation of enzymes.

Plasma enzymes as diagnostic tools

Enzymes present in blood can indicate tissue damage or disease when their levels are abnormal.

Protein misfolding and disease

Misfolded proteins can aggregate; associated with amyloid diseases and prion diseases.

Amyloid diseases

Disorders involving insoluble aggregates of misfolded β-pleated sheet proteins, linked to neurodegenerative diseases.

Prion diseases

Infectious protein misfolding diseases caused by PrPSc; include Creutzfeldt-Jakob disease and mad cow disease.

Isoforms vs isozymes

Isoforms (proteins with the same function but different sequences); isozymes (enzyme variants that catalyze the same reaction).