Peptide bond formation is not spontaneous (favorable in free energy) under normal conditions, and requires conversion of the carboxyl or the amino group to a form which reacts more readily. In general, the carboxylic acid moiety is activated by converting it to an ester, acid chloride, anhydride, azide or some other derivative that makes the carbonyl group more nucleophilic. Note that once you make a peptide bond, the peptide backbone is fairly chemically inert: the nitrogen is no longer as strong a nucleophile, and the linkage is pretty stable and slow to hydrolyze. Proteins are typically digested exhaustively by heating to near boiling temperatures in reasonably strong solutions of hydrochloric acid. As we will learn later, there are of course enzymes that hydrolyze proteins quite efficiently.
Amino acid and protein chemistery
Proteins are the most abundant and functionally diverse molecules in living systems where they constitute 50% or more of their dry mass.The word protein is derived from the Greek Protos, which means the first or supreme.Proteins are nitrogenous macromolecules,composed of aminoacids linked by peptide bond.
AMINO ACIDSAmino acids are organic solvents.Have two functional groups –NH₂ and -COOH group.The amino group is basic while carboxylic group is acidic in nature.Soluble in water but insoluble in organic solvents e.g chloroform,acetone,ether,etc.All amino acids which make up proteins are L-α- aminoacids.All amino acids have chiral carbon, exept Glycine.
LOW pH NEUTRAL HIGH pH O O OR C R C R C OH O O NH3 NH3 NH2ammonium Form Zwitterion Carboxylate Form
CLASSIFICATION OF AMINO ACIDSAlthough more than 300 naturally occurring amino acids are known but only 20 amino acids take part in the formation of all types of proteins,plants as well as animal in origin.These 20 amino acids are known as Primary,Standard or normal amino acids.
Each of these amino acids has one or more genetic codon(s) which are present within the molecules of specific mRNA which themselves are produced under direction of genes occuring in DNA molecules.
Semi-essential aminoacids. These include Arginine and Histidine.These are growth promoting factors since they are not synthesized in sufficient quantity during growth.
Others includeN-methyllysine,Found in myosinCarboxyglutamate,Found in ProthrombinDesmosine,Found in elastin
Non protein amino acidsThese are the amino acids which donot take part in the protein synthesis, and have no genetic codes.They perform other functions in human metabolism e.g
6.CitrulineOrnithineArgininosuccinic acidThese three amino acids occur in the liver,where they takepart in the formation of urea.
7.Pantathenic acid. It is a widely distributed vitamin.It forms a part of the molecule of Co.enzymeA.8.Homocysteine
Proteins are made by controlled polymerization of amino acids water is eliminated O Otwo amino acids H2N CH C OH H2N CH C OHcondense to form... R1 R2 N or amino C or carboxy terminus O O terminus...a dipeptide. If H2N CH C NH CH C OH + HOHthere are more itbecomes a polypeptide. R1 R2Short polypeptide chainsare usually called peptideswhile longer ones are called peptide bond is formedproteins. residue 1 residue 2
Classification of peptidesDIPEPTIDESOLIGOPEPTIDES Composed of 3-10 amino acids linked together through peptide bond.e.g Tripeptide(3 amino acids linked together by 2 peptide bonds),Tetrapeptide(4 amino acids linked together by 3 peptide bonds).
UNUSUAL PEPTIDE BONDIn some cases the peptide bond in a peptide does not involve α-COOH group.e.g Glutathione which has the sequence glutamic acid,cysteine and glycine.However,the –COOH group of glutamic acid forming peptide bond with cysteine is not α but γ.For this reason glutathione is chemically γ-glutamyl- cysteinyl-glycine.
CLASSIFICATION OFPROTEINS ON THE BASIS OF MOLECULAR LENGTH AND SHAPE.Fibrous proteins. When the axial ratio of length:width is more than 10.e.g collagen,α keratin of hair.Globular proteins. When axial ratio of length:width of protein molecule is less than 10.e.g Myoglobin,haemoglobin,ribonucleases.
ON THE BASIS OF SOLUBILITY AND PHYSICAL PROPERTIES.Simple proteinsConjugated proteinsDerived proteins
SIMPLE PROTEINS These are the proteins which on complete hydrolysis yield only amino acids.They are further classified based on their solubilities and heat coagulabilities.1.ALBUMINSoluble in waterPrecipitated by full saturation with ammonium sulfateCoagulated by heatExamples,Ovalbumin.serum albumin,lactalbumin and legumel
2.GlobulinsInsoluble in water,soluble in dilute salt solutions.Heat coagulablePrecipitated by half saturation with ammonium sulfate.Examples,serum globulins,lactoglobulin,myosin in muscles,ovoglobulin and legumin.
3.GlobinsRich in histidine but not basic.Combine with heme to form hemoglobin.4.ProlaminsSoluble in ethanol,insoluble in water.Rich in amino acid proline but deficient in lysine.Examples,gliadin of wheat and zein of maize.
5.Protamines.Basic proteins,soluble in NH4OH.Rich in arginine,lack tyrosine and tryptophan.Form nucleoproteins with nucleic acids.Present in sperm cells.
6.HistonesStrongly basic proteins as they are rich in arginine.Form nucleoproteinsSoluble in water.Lack tryptophan
7.AlbuminoidsAlso called scleroproteins,occur only in animals donot occur in plants.Include collagen,keratin and elastin.
COPOUND OR CONGUGATED PROTEINSThese are the proteins which in addition to amino acids contain contain a non protein group called prosthetic group in their structure.1.NucleoproteinsHistones+nucleic acidsMost abundant in tissues having a large proportion of nuclear material e.g yeast,thymus and other glands and sperms.
2.PhosphoproteinsSimple proteins+phosphoric acidExamples casein of milk and vitellin of egg yolk.3.LipoproteinsSimple proteins+covalently bonded with lipid substances like lecithin,cholesterol,triglycerides and fatty acids.Occur in blood plasma,nervous tissue,egg yolk,milk and cell membrane.Bacterial antigens and viruses also contain lipoproteins.
DERIVED PROTEINSInclude proteins derived from simple and conjugated proteins.1.Primary derived proteinsSynonymus with denatured proteins.Denaturation takes place when some or all of the cross linkages which normally keep the molecular of protein intact are split,although there is no hydrolysis of protein molecule.
Denaturation may be brought about by chemical or physical agents such as heat,X rays,ultrasonic waves,shaking or stirring for long time,extremes of pH,salts of heavy metals,neutral chemical agents such as urea and organic solvents such as alcohol and acetone.In most cases denaturation is irreversible,but in some cases it is reversibleExample,RIBONUCLEASE.(Denaturation is reversible)
Secondary derived proteinsThese substances are intermediates formed in the progresive hydrolysis of protein molecule.They are of different sizes and different amino acid composition.PROTEOSESSoluble in water,coagulated by heat,and are precipitated from their solution by saturation with ammonium sulphate.PEPTONESPOLYPEPTIDESOLIGOPEPTIDES
Classification based on function.Catalytic proteinsRegulatory or hormonal proteinsTransport prpoteinsImmune proteinsContractile proteinsGenetic proteins
Classification of proteins regardingnutritionHIGH QUALITY PROTEINSLOW QUALITY PROTEINS