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. WHen weak acid is greater than conjugate base pH > pKa

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

Max Buffering Capcity

When ph= pKa

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 When Form 1 = 23(the Amino acid is electrically neutral) (form 2 Predominates

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 (proteaese)

Enzymes that hydrolyze peptide bonds;

exopeptidases

cut at the end of ptoteins

aminopeptidases

cuts amino end

carboxypeptidases

cuts carboxyl end

endopeptidases

cleaves within a protein

N-terminus and C-terminus

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

residue

each component AA

Naming polypeptides

AA have their suffixes changed to -yl with exception of C terminal

N- valine- glycine- leucine: vallyglylyleucine

Trans vs cis peptide bonds

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

Stop Codons

UAA UGA UAG

Which protein contains a-helices

Keratain (most common protein) (hair nail skin) Myoglobin too

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. (side by side)

Tertiary structure

Three-dimensional folding of a single polypeptide; stabilized by hydrogen bonds, disulfide bonds, ionic interactions, and hydrophobic effects by side chains which are attracted and repulsed

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, strong acid and bases, detergents, heavy metals, organic solvents, and mechanical mixing (may or may not be reversible)

What is dental amalgam

mixture of metals including mercury

Quaternary structure

3D structure formed by the assembly of multiple polypeptide chains; subunits may be independent or cooperative. (held together by noncovalent interactions: Hbonds ionic bonds and hydrophobic interactions)

Protein Misfolding

caused from trial and error

are tagged and degraded by cell by unqiuloine

can accumalte due to age

Amyloid Disease

accumuation of insoluble, spontanous aggregating misfolder protein called amyloid of Beta- pleated sheets

leads to alzherim and Parkison (affects nervous system)

Prion Diseases

caused by prion protein (prp)

highly resistant to proteolytic degreading

TSE → causative agent that leads to Creutzfeldt-Jacob disease in human, scrapie in sheep and mad cow disease

Infections Prp Sc
noninfection: prpC

Prp Sc includes a 3D confimation change in PrpC that is resistant to degradition

Structure and Function of Myoglobin

Function: Resrvoir for oxygen and carrier that increases rate of transport of O2 within the muscle cell

Structure Consists of a single polypetide chain with a heme group

Structure and function of Hemoglobin

Found in RBC
Function: transport O2 from lungs to capillaries of tissues and also tranport H+ and Co2 from tissues to the lungs

Structure: Transport 4 molecules of O2 on its 4 heme group

Hemoglobin A (HB A )

consists of 4 polypeptide chains - 2a and 2B by non covlanet

each subunit has stretches of a-helical and heme binding pocket

Forms of HBa

Oxgeated form = R relaxed state

Deoxygenated form T Taut State

O2 dissociation curve

Hemo :Sigmodial shape
myogolbin : hyperbolic shape

Cooperative binding

as O2 binds the binding of O2 is enhanced

Location of O2 and its affinity for O2

Lungs: hemo quickly saturauted
Tissues: gives up about half O2

myoglobin has a greater for O2 especially when O2 is very low in muscle cells(strenous activity)

bohr effect

The effect a change in O2 binding affinity of Hb due to the binding of other ligands to Hb

ligands include:
(H+ pH) increase in Ph leads to shift right -→ decreasing O2 affinity

2,3 Biphosphoglveryate Increased leads to decreaed binding for affinity O2 (shift right)

Co2 Increased leads to decreased affinity = shift right

These ligands stablilze the T state deoxygented form of O2

Carbon Monoxide

CO binding to 4 heme sites leads to increased affinity of O2 binding it tightly and it cant release leading to no celluar respiration

Hemoglobinopathies

genetric disorders of hemoglobin due to structural abnoramilies, insufficent quaitines of normal Hb or both

Ex.
sickle cell anemia (Hb S)- glutatmete is substitued with valine
Hemoglobin C (HB C) glutatmte is sub with lysine
H SC (HB S+C)
Thallaseeia syndrome: decreased proection of normal HBC

Globular vs Fibrous Proteins

Globular are funcational Hemoglobin and Myoglobin
Fibrourous are structure (collagen elastic and a-keratin)

Collagen

Most abduant in human Body, 3 polypeptide helices
Type 1 is found in teeth, bone, skins, and tendons

AA comp of collage is distinctive
1. glycine- approx 1/3 of AA residue
2. Proline and 4-hydroyproline 30%

Hydroxproline and hydroxylysine are NOT PRESENT IN MOST OTHER PROTEINS

Hydroxyproline

Post-translationally modified proline; important for collagen stability.

Elastin

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

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.

Globular vs fibrous proteins (recap)

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

Biosysthesis Of Collagen

#3 selected proline and lysine residues hydroxylated (vitamin C importeter here)
#4 Triple helix is formed and procollagen is produced
#8 N and C are cleaved by procollage peptidaes producing tropocollage

Defects of Collagen Sysnthesis

Ehlers Dalos sydrome= fragile stretchy skin and loosejoints
Osteogensis imperfect = bones that bend and fracture easily

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).

Oxidoreductase

changes OH to a O=

Transferase

transfer functional groups between substrates

hydrolase

catalyzes the hydrolysis of chemical bonds, breaking down larger molecules into smaller ones by adding water.

lyase

catalyze the breaking of bonds by means of a reverse reaction of hydration. breaking off a bond

isomerase

catalyzes the conversion of a molecule from one isomer to another, altering its structure without adding or removing atoms.

ligase

catalyzes the joining of two molecules by forming a new bond, typically accompanied by the consumption of ATP.

translocase

moves molecules across or within membrane

Synthase

catalzyes a synthesis process

synthetase

catalyzes a sysnthesis process and requires ATP or another nucleotirde triphosphate

Phosphatase

removes phosphate group

Phosporylase

breaks bond by adding inogrnic group

Kinase

transfer a phosphate group from a hige energy molecucle such as ATP

Oxidase

an enzyme that catalyzes oxidation reduction rxn using O2 as E acceptor (removing e-)

Oxygenase

oxidize a subsrate by trasnferring oxygen atoms to it (adding e-)

Properties of Enzymes

Active Site: contains AA side chain that does substrate binding and cataylsis

effcient: faster than uncatalzyed reaction
specific: interactis with one or few substrate
regulated: can be regulated Increased/decreased so rate of product formation responds to cellular needs

location: in specific organelles within the cell

Holoenzyme vs apoenzyme

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

Cofactor vs Coenyzme

Cofactor is a non-protein chemical compound that is required for the biological activity of a protein, while coenzyme is a specific type of cofactor, often an organic molecule, that assists enzyme function.