Biochemistry for Environmental Health Lecture 3-Amino Acid & Protein

Ahmad Razali IshakDepartment of Environmental HealthFaculty of Health SciencesUiTM Puncak Alam1

Lecture 3-Amino Acid & ProteinFunction of ProteinCatalysts- enzymes for metabolic pathwayStorage and transport- myoglobin and hemoglobinStructural- actin, myosinDecoding information- translation and gene expressionHormones and hormone receptorsSpecialized functions-antibodies

Amino Acids- Primary structure of proteinAmino acid: a compound that contains both an amino group and a carboxyl group -Amino acid has an amino group attached to the carbon adjacent to the carboxyl group-carbon also bound to side chain group, RR gives identity to amino acid

Cont..The - carbon is chiral/asymmetric (4 different groups are attached to the carbon: exception is glycine )- mirror image, non super imposable

AA exist as stereoisomer (same molecular formula, but differ in arrangement of groups) designated D (right) or L (Left)

Vast majority of -amino acids have the L-configuration at the -carbon (Proline is usually D)

-amino group orientation determines L or DNH3+ on left = LNH3+ on right = DCarboxylate group at top- point away side chain at the bottomAA structure and propertiesAA are grouped based upon the properties and structures of side chainsAliphatic (R groups consist of carbons and hydrogens)-Glycine, Alanine, Valine, Leucine, Isoleucine, Proline

Sulfur containing R group- methionine, cysteine

Aromatic (R group have phenyl ring)- Phenylalanine, tyrosine

Polar R group - Ser, Thr, Tyr, Cys, Glu

Non Polar R group - Ala, Val, Leu, Ile, Pro. Phe, Trp, Met.

Cont..Basic R group- Histidine, lysine, arginineAcidic R group - Glutamate, AspartateSide chain with alcohols Serine, threonine

Ionization of Simple Amino AcidsAmino acids are more complicated than simple weak acids since amino acids have at least 2 ionizing groups.Glycine (abbrevation is Gly), for example, has both a carboxylic acid and an amino group that can ionize:

If we dissolve the free base of Gly in pure water (ie neutral pH), it will ionize.The equilibrium is far to the right so most of the Gly is in the charged form called the Zwitterion and Gly is still neutral because the + charge is neutralized by the - charge. Gly is always in the Zwitterion form at neutral pH.

Ionization of Amino Acids Remember, amino acids without charged groups on side chain exist in neutral solution as zwitterions with no net charge

If one aa being titrated from acidic condition, you will get this titration curveE.g. Titration curve for glycine

At given pH, amino acid have different net chargeThe isoelectric point (pI) is the pH at which the amino acid has no net charge = zwitterionIf pH > pI, amino acid would be ve chargedIf pH < pI, amino acid would be positively charged Isoelectric pHIsoelectric pH, pI: the pH at which the majority of molecules of a compound in solution have no net charge

the pI for glycine, for example, falls midway between the pKa values for the carboxyl and amino groups

Isoelectric pH values for the 20 protein-derived amino acids are given in Table 3.2

Protein StructureFour Levels of Protein Structure:1. Primary Structure- Polypeptide backbone- Linear sequence of amino acid2. Secondary Structure- regular patterns formed by primary structure folding-Local Hydrogen bonds along the backbone3. Tertiary structure- Completely folded polypeptide with one or more domains. Long distance bonding involving the AA side chains4. Quaternary structure- Association of multiple polypeptides. Protein interactions leading to formation of dimers, tetramers, etc.

Protein Covalent Structure (Protein Primary Structure)I. Peptide Bonds, Peptides and ProteinsProteins are sometimes called Polypeptides, since they contain many Peptide Bonds

The peptide bond is an amide bondWater is lost in forming an amide bond.Comparison of an amino acid, a dipeptide and a tripeptide

Peptides = Mini-Proteins

A pentapeptide -- GlyAlaSerPheGln1st amino acid is always written on the left and called the Amino terminal, since it is always the only amino acid of the peptide with a free alpha-amino group. Last amino acid is always written on the right and called the Carboxyl terminus, since it is always the only amino acid of the peptide with a free alpha-carboxylic acid group.SECONDARY STRUCTURE OF PROTEINSIn 1950's, Linus Pauling named the first structures he found by X-ray diffraction, the Alpha Helix and the second structure he found was called Beta Sheet

The 2 COMMON Types of Protein Secondary Structure:Alpha-helixBeta-sheet

-HelixCoil of the helix is clockwise or right-handedThere are 3.6 amino acids per turnRepeat distance is 5.4Each peptide bond is s-trans and planarC=O of each peptide bond is hydrogen bonded to the N-H of the fourth amino acid awayC=O----H-N hydrogen bonds are parallel to helical axisAll R groups point outward from helix-Helix (Contd)

-Pleated SheetPolypeptide chains lie adjacent to one another; may be parallel or antiparallelR groups alternate, first above and then below planeEach peptide bond is s-trans and planarC=O and N-H groups of each peptide bond are perpendicular to axis of the sheetC=O---H-N hydrogen bonds are between adjacent sheets and perpendicular to the direction of the sheet-Pleated Sheet (Contd)

-Pleated Sheet (Contd)-bulge- a common nonrepetive irregular 2 motif in anti-parallel structure

MyoglobinA single polypeptide chain of 153 amino acidsA single heme group in a hydrophobic pocket8 regions of -helix; no regions of -sheet

Quaternary StructureQuaternary (4) structure: the association of polypepetide monomers into multisubunit proteins dimers trimers tetramers

Noncovalent interactions electrostatics, hydrogen bonds, hydrophobicHemoglobin (Hb)A tetramer of two -chains (141 amino acids each) and two -chains (153 amino acids each); a2b2

HomeworkDescribe the difference between alpha-helix and beta-sheet protein structures.Describe the metabolic disorder of protein- phenylketonuriaPlease upload the answer in the i-discuss before next seminar