Chemistry of amino acids

By

DR. AMR SALAH ABOUZIEDASSISTANT PROFESSOR OF ORGANIC CHEMISTRY AT

COLLEGE OF PHARMACY, HAIL UNIVERSITY

Amino Acids

• Amino Acids are the building units of proteins. Proteins are polymers of amino acids linked together by what is called “ Peptide bond”.

• There are about 300 amino acids occur in nature. Only 20 of them occur in proteins.

• Each amino acid has 4 different groups attached to α- carbon ( which is C-atom next to COOH). These 4 groups are : amino group, COOH gp, Hydrogen atom and side, Chain (R)

R

• At physiological PH (7.4), -COOH gp is dissociated forming a negatively charged carboxylate ion (COO-) and amino gp is protonated forming positively charged ion (NH3+) forming Zwitter ion

• Amino acid structures differ at the side chain (R-groups).

• Abbreviations: three or one letter codes• Amino acids (except glycine) have chiral centers: • Rotate the plane of polarized light and are optically

active.• There are 20 commonly occurring amino acids that

make up proteins, and the order of amino acids in proteins determines its structure and biological function.

• When amino acids are covalently linked to one another, this chain can twist and fold to form a unique three-dimensional structure that has a specific function.

Amino Acid Structure

• Amino acids contain two functional groups, a protonated amine and carboxylic acid in the form of a carboxylate group.

• Amino acid carbons are named in sequence using the Greek alphabet (, , , , ) starting at the carbon between the carboxyl and amino groups.

CH

COO

H3N

CH2

CH2

CH2

CH2

NH3

• The carbon is also bonded to a hydrogen atom and a larger side chain. The side chain is unique for each amino acid.

• An amino acid, with a chiral center, has two forms called enantiomers, which are nonsuperimposable mirror images.

• When drawing the Fischer projection, the carboxylate group is at the top of the structure and the side chain (R group) is at the bottom.

• The protonated amine group can be on the left-hand side (L form) or right-hand side (D form) of the structure.

• The L-amino acids are the building blocks for proteins. Some D-amino acids occur in nature, but not in proteins.

• BUT L or D designation for an amino acid does NOT reflect its ability to rotate plane polarized light in a particular direction!

C

COO

H3N

CH3

HC

COO

H3N

CH3

H

(S)-AlanineL-Alanine

C

H

H3C

NH3

COO

1

23

S

• The R group gives each amino acid its unique identity and characteristics.

• Twenty amino acids are found in most proteins.• There are nine different families of organic

compounds represented in the structures of different amino acids. They are as follows:

1. Alkanes

2. Aromatics

3. Thioethers

4. Alcohols

5. Phenols

6. Thiols

7. Amides

8. Carboxylic acids

9. Amines

Classification of amino acids

Amino acids can be classified in 4 ways:1. Based on structure2. Based on the side chain characters3. Based on nutritional requirements4. Based on metabolic fate

1)Classification based on structure

• According to number of COOH and NH2 groups i.e. according to net charge on amino acid.

• i) Aliphatic Amino Acids

A- Monobasic, monocarboxylic amino acids i.e. neutral or uncharged:

R

1- Glycine R= H 2- Alanine R= CH3

3- Branched chain amino acids: R is branched such as in: a - Valine R= isopropyl gp

b- Leucine R= isobutyl gp

c- Isoleucine R= isobutyl gp

R is isobutyl in both leucine and isoleucine but branching is different: in leucine → branching occurs on γ carbon in isoleucine→ branching occurs on β- carbon

4- Neutral Sulfur containing amino acids:

e.g. Cysteine and Methionine.

5- Neutral, hydroxy amino acids:

e.g. Serine and Threonine

6- Amide group-containing amino acids:

e.g. Glutamine and Asparagine

i) Aliphatic Amino AcidsB- Mono-amino di-carboxylic acids (Acidic): Aspartic acid and Glutamic acid

i) Aliphatic Amino Acids:C- Di- basic mono-carboxylic acids(Basic): Arginine and Lysine

ii ) Aromatic amino acids Phenyl alanine and tyrosine

iii) Heterocyclic Amino Acids: Tryptophan and Histidine

iv) Imino acid- Proline: In proline, amino group enters in the ring formation being α-imino gp so proline is an α-imino acid rather than α-amino acid

v) Derived Amino Acids: Non-α-amino acids

e.g.: β-alanine, γ-amino butyric acid (GABA), δ-amino Levulinic acid

Derived and Incorporated in tissue proteins:e.g.: Hydroxy-proline, hydroxy-lysine

Derived but not incorporated in tissue proteins:e.g.: Ornithine, Citrulline, Homocysteine, Argino succinic acid

2) Classification based on side chain characters

A. Amino Acids with a Non-polar side-chain:e.g.: Alanine, Valine, Leucine, Isoleucine,

Phenylalanine, Tryptophan, Proline

Each of these amino acids has a side chain that does not bind or give off protons or participates in hydrogen or ionic bonds.

Side chains of these amino acids can be thought of as “Oily” or lipid like, a property that promotes hydrophobic interactions.

B) Amino acids with a polar but uncharged side-chain:e.g. Serine, Threonine, Tyrosine, Cysteine, Asparagine and Glutamine.

These amino acids are uncharged at neutral pH,although the side chains of cysteine and Tyrosinecan lose a proton at an alkaline pH.Serine , Threonine and Tyrosine each contains a polar hydroxyl group that can participate in hydrogen bond formation. Side chains of Asparagine and Glutamine contain a carbonyl group and amide group, they

can also participate in hydrogen bond formation.

C) Amino acids with a charged side-chaina) Amino acids with a positively charged side-

chain:The basic amino acids- Lysine, Arginine and Histidineb) Amino acids with a negatively charged side-

chain:• The acidic amino acids- Glutamic acid

and Aspartic acid• They are hydrophilic in nature.

3)- Classification based on nutritional requirements

I. Essential amino acids:These amino acids cannot be synthesized in the body and have to be present essentially in the diet. Examples-Valine, Isoleucine, Leucine, Lysine, Methionine, Threonine, Tryptophan and Phenylalanine.

II. Semi-essential amino acids:These amino acids can be synthesized in the body but the rate of synthesis is lesser than the requirement(e.g. during growth, repair or pregnancy) Examples-Arginine and Histidine.

III. Non-essential amino acids:These amino acids are synthesized in the body, thus their absence in the diet does not adversely affect the growth.Examples- Glycine, Alanine, and the other remaining amino acids.

Essential AA Nonessential AAHistidine AlanineIsoleucine Arginine **Leucine AsparagineLysine Aspartic AcidMethionine Cysteine **Phenylalanine Glutamic acidThreonine Glutamine **Tryptophan Glycine **Valine Proline **

SerineTyrosine **

4)-Classification based on metabolic fate

The carbon skeleton of amino acids can be used either for glucose production or for the production of ketone bodies, Based on that I. Both glucogenic and ketogenic amino acids:

Isoleucine, Tyrosine, Phenylalanine and TryptophanII. Purely Ketogenic amino acids:

Leucine and LysineIII. Purely Glucogenic amino acids:

The remaining 14 amino acids are glucogenic. Alanine, valine ,serine, threonine, glycine, methionine, asparagine, glutamine, cysteine, cystine, aspartic acid, glutamic acid, histidine and arginine.

Non standard amino acidsOf the over 300 naturally occurring amino acids, 20 constitute the monomer units of proteins. These 20 amino acids are called the Primary or Standard amino acids.Seleno cysteine is the 21st Amino AcidThe other are Pyroglutamate and Pyrolysine.

Naming of Amino acids

Each amino acid has three letter (code) and one letter (Symbol) abbreviations- Examples-1) Unique first letterCysteine- Cys- CHistidine- His- H2) Priority of commonly occurring amino acidsAlanine- Ala- A (Preference over Aspartate) Glycine- Gly-G (Preference over Glutamate)

Naming of Amino acids3) Similar sounding names- Some one letter symbols sound like the amino acids they represent- Example Tryptophan – W (Twyptophan) Phenyl alanine – F4) Letters close to initial letterAspartate- Asx- B( near A)Lysine Lys- K(near L)

Amino acid abbreviations

Special groups in amino acids

Arginine- Guanidinium groupPhenyl Alanine- Benzene group Tyrosine- Phenol groupTryptophan- Indole group Histidine- Imidazole groupProline- Pyrrolidine Proline has a secondary amino group, hence it is an imino acid.

Properties of amino acids

Physical properties-ColorlessCrystallineMay be sweet(Glycine, Alanine, Valine), tasteless(Leucine) or bitter(Arginine, Isoleucine). Aspartame- An artificial sweetener contains Aspartic acid and Phenyl alanine.Soluble in water, acids, alkalis but insoluble in organic solventsHigh melting point(More than 2000c)

Isoelectric point

Amino acids can exist as ampholytes or zwitterions in solution, depending upon pH of the medium.The pH at which the amino acids exist as zwitterions, with no net charge on them is called Isoelectric pH or Isoelectric point.In acidic medium, the amino acids exist as cationsIn alkaline medium , they exist as anions.

Due to no net charge, there is no electrophoretic mobility at Isoelectric pH.Solubility and buffering capacity are also minimum at Isoelectric pH

Isoelectric point

Isoelectric pH• pH at which amino acids exist as the zwitterion

(neutral) and carries no net charge. Thus molecule is electrically neutral.

• The pl value can be calculated by taking the average pKa values corresponding to the ionizable groups. For example leucine has two ionizable groups , and its pl value can be calculated as follows.

• Leucine exists as cation at pH below 6 and anion at pH above 6. at the ispelectric pH leucine is found as Zwitterions .

• Titration curve of Amino acid: in the graphical representation of Leucine titrarion at low pH , Leucine exists in fully protonated forms as cation. As the titration proceeds with NaOH, Leucine loses its protons and at isoelectric pH its become Zwitterions. Further titration results in formation of anionic form of Leucine.

The isoelectric point (pI) of an amino acid is the pH atwhich it has no net charge

Structure and pH

Optical properties of amino acidsThe α carbon of each amino acid is attached to four different groups and is thus a chiral or optically active carbon atom.Glycine is exceptional because there are two hydrogen substituents at the α carbon, thus it is optically inactive.Amino acids with asymmetric centre at the α carbon can exist in two forms, D and L forms that are mirror images of each other and are called Enantiomers.All amino acids found in proteins are of L- configurationD- amino acids are found in some antibiotics and in bacterial cell walls.

L & D isomers of amino acids

Synthesis of α-Amino Acids

1- Amination of alpha-bromocarboxylic acids provides a straight forward method for preparing alpha- aminocarboxylic acids. The bromoacid are conveniently prepared from carboxylic acids by reaction with Br2 + PCl3.

2- Gabriel synthesis

Explanation of Gabriel Synthesis• By modifying the nitrogen as a phthalimide salt the propensity of

amines to undergo multiple substitutions is removed, and a single clean substitution reaction of 1º- and many 2º-alkylhalides takes place.

• Since the phthalimide substituted malonic ester has an acidic hydrogen (colored orange) activated by the two ester groups, this intermediate may be converted to an ambident anion and alkylated.

• Finally, base catalyzed hydrolysis of the phthalimide moiety and the esters, followed by acidification and thermal decarboxylation, produces an amino acid and phthalic acid (not shown).

4- Resolution Method • Resolution   The three synthetic procedures described above

and many others that can be conceived, give racemic amino acid products. If pure L or D enantiomers are desired, it is necessary to resolve these racemic mixtures.

• A common method of resolving racemates is by diastereomeric salt formation with a pure chiral acid or base.

• This is illustrated for a generic amino acid in the following diagram. Be careful to distinguish charge symbols shown in colored circles, from optical rotation signs shown in parenthesis.

3- Strecker Synthesis• assembles an alpha-amino acid from ammonia (the amine

precursor), cyanide (the carboxyl precursor) and an aldehyde. This reaction is essentially an imino analog of cyanohydrin formation. The alpha-amino nitrile formed in this way can then be hydrolyzed to an amino acid by either acid or base catalysis.

• Explanation of Resolution Method• In the initial display, the carboxylic acid function contributes to diastereomeric salt

formation.• The racemic amino acid is first converted to a benzamide derivative to remove the

basic character of the amino group. • Next, an ammonium salt is formed by combining the carboxylic acid with an

optically pure amine, such as brucine (a relative of strychnine). • The structure of this amine is not shown, because it is not a critical factor in the

logical progression of steps. • Since the amino acid moiety is racemic and the base is a single enantiomer

(levorotatory in this example), an equimolar mixture of diastereomeric salts is formed (drawn in the green shaded box).

• Diastereomers may be separated by crystallization, chromatography or other physical manipulation and in this way one of the isomers may be isolated for further treatment, in this illustration it is the (+):(-) diastereomer.

• Finally the salt is broken by acid treatment, giving the resolved (+)-amino acid derivative together with the recovered resolving agent (the optically active amine). Of course, the same procedure could be used to obtain the (-)-enantiomer of the amino acid.

• Since amino acids are amphoteric, resolution could also be achieved by using the basic character of the amine function. For this approach we would need an enantiomerically pure chiral acid such as tartaric acid to use as the resolving agent.

• Note that the carboxylic acid function is first esterified, so that it will not compete with the resolving acid.

Resolution of aminoacid derivatives may also be achieved by enzymatic discrimination in the hydrolysis of amides. For example, an aminoacylase enzyme from pig kidneys cleaves an amide derivative of a natural L-amino acid much faster than it does the D-enantiomer.

• If the racemic mixture of amides shown in the green shaded box above is treated with this enzyme, the L-enantiomer (whatever its rotation) will be rapidly converted to its free zwitterionic form, whereas the D-enantiomer will remain largely unchanged.

• the diastereomeric species are transition states rather than isolable intermediates.

• This separation of enantiomers, based on very different rates of reaction is called kinetic resolution.

5- Petasis Reaction

Reactions of amino acids

1) Reactions due to amino group2) Reactions due to carboxyl group

3) Reactions due to side chain4) Reaction due to both amino and carboxyl

groups

Reactions due to amino group

Oxidative deamination-α amino group is removed and corresponding α-keto acid is formed. α-keto acid produced is either converted to glucose or ketone bodies or is completely oxidized.

Transamination-Transfer of an α amino group from an amino acid to an α keto acid to form a new amino acid and a corresponding keto acid.

Reactions due to amino group

Formation of carbamino compoundCO2 binds to α amino acid on the globin chain of hemoglobin to form carbamino hemoglobinThe reaction takes place at alkaline pH and serves as a mechanism for the transfer of Carbon dioxide from the tissues to the lungs by hemoglobin.

Reactions due to carboxyl group

1) Decarboxylation- Amino acids undergo alpha decarboxylation to form corresponding amines. Examples-

Glutamic acid GABA Histidine Histamine

Tyrosine Tyramine

2) Formation of amide linkage• Non α carboxyl group of an acidic amino acid reacts with

ammonia by condensation reaction to form corresponding amides

Aspartic acid Asparagine Glutamic acid Glutamine

Reactions due to side chains

1) Ester formation OH containing amino acids e.g. serine,

threonine can form esters with phosphoric acid in the formation of phosphoproteins.

OH group containing amino acid can also form: Glycosides – by forming

O- glycosidic bond with carbohydrate residues.

Reactions due to side chains

2) Reactions due to SH group (Formation of disulphide bonds)Cysteine has a sulfhydryl group( SH) group and can form a disulphide (S-S) bond with another cysteine residue. The dimer is called CystineTwo cysteine residues can connect two polypeptide chains by the formation of interchain disulphide chains.

Formation of disulphide bond

Reactions due to side chains

3)Transmethylation

The methyl group of Methionine can be transferred after activation to an acceptor for the formation of important biological compounds.

4)Reactions due to both amino & carboxyl groupsFormation of peptide bond

Reactions due to side chains

Special functions of Amino acids

Incorporated in to tissue proteins Niacin, Serotonin and melatonin are synthesized from TryptophanMelanin, thyroid hormone, catecholamines are synthesized from TyrosineGABA (neurotransmitter) is synthesized from Glutamic acidNitric oxide, a smooth muscle relaxant is synthesized from Arginine. Act as precursors for haem, creatine and glutathione, Porphyrins, purines and pyrimidines.

Colour reactions of amino acidsS.No. Test Significance

1) Ninhydrin reaction Given by all Alpha amino acids

2) Xanthoproteic test Given by aromatic amino acids

3) Millon’s test Confirmatory test for Tyrosine

4) Biuret test Not given by free amino acids

5) Sakaguchi test Given by Arginine

6) Hopkins Cole reaction Confirmatory test for Tryptophan

7) Lead acetate test Given by cysteine and cystine but not given by Methionine

8) Nitroprusside reaction Given by SH group containing amino acids

Peptides and Proteins20 amino acids are commonly found in protein.These 20 amino acids are linked together through “peptide bond forming peptides and proteins (what’s the difference?). - The chains containing less than 50 amino acids are called “peptides”, while those containing greater than 50 amino acids are called “proteins”.

Peptide bond formation:α-carboxyl group of one amino acid (with side chain R1)

forms a covalent peptide bond with α-amino group of another amino acid ( with the side chain R2) by removal of a molecule of water. The result is : Dipeptide ( i.e. Two amino acids linked by one peptide bond). By the same way, the dipeptide can then forms a second peptide bond with a third amino acid (with side chain R3) to give Tripeptide. Repetition of this process generates a polypeptide or protein of specific amino acid sequence.

Peptide bond formation:

- Each polypeptide chain starts on the left side by free amino group of

the first amino acid enter in chain formation . It is termed (N- terminus).

- Each polypeptide chain ends on the right side by free COOH group of

the last amino acid and termed (C-terminus).

Examples on Peptides: 1- Dipeptide ( tow amino acids joined by one peptide bond):Example: Aspartame which acts as sweetening agent being used in replacement of cane sugar. It is composed of aspartic acid and phenyl alanine.

2- Tripeptides ( 3 amino acids linked by two peptide bonds).Example: GSH which is formed from 3 amino acids: glutamic acid, cysteine and glycine. It helps in absorption of amino acids, protects against hemolysis of RBC by breaking H2O2

which causes cell damage.

3- octapeptides: (8 amino acids)Examples: Two hormones; oxytocine and vasopressin (ADH).

4- polypeptides: 10- 50 amino acids: e.g. Insulin hormone

Protein structure:There are four levels of protein structure (primary, secondary, tertiary and quaternary)

Primary structure: • The primary structure of a protein is its unique sequence of

amino acids.– Lysozyme, an enzyme that attacks bacteria, consists of a

polypeptide chain of 129 amino acids.– The precise primary structure of a protein is determined by

inherited genetic information.– At one end is an amino acid with a free amino group the

(the N-terminus) and at the other is an amino acid with a free carboxyl group the (the C-terminus).

High orders of Protein structure • A functional protein is not just a polypeptide chain, but one or more polypeptides

precisely twisted, folded and coiled into a molecule of unique shape (conformation). This conformation is essential for some protein function e.g. Enables a protein to recognize and bind specifically to another molecule e.g. hormone/receptor; enzyme/substrate and antibody/antigen.

•

2- Secondary structure: Results from hydrogen bond

formation between hydrogen of –NH group of peptide bond and the carbonyl oxygen of another peptide bond. According to H-bonding there are two main forms of secondary structure:

α-helix: It is a spiral structure resulting from hydrogen bonding between one peptide bond and the fourth one β-sheets: is another form of secondary

structure in which two or more polypeptides (or segments of the same peptide chain) are linked together by hydrogen bond between H- of NH- of one chain and carbonyl oxygen of adjacent chain (or segment).

Hydrogen bonding in α-helix: In the α-helix CO of the one amino acid residue forms H-bond with NH of the forth one.

Supersecondary structure or Motifs : occurs by combining secondary structure.The combination may be: α-helix- turn- α-helix- turn…..etc Or: β-sheet -turn- β-sheet-turn………etc Or: α-helix- turn- β-sheet-turn- α-helixTurn (or bend): is short segment of polypeptides (3-4 amino acids) that connects successive secondary structures.e.g. β-turn: is small polypeptide that connects successive strands of β-sheets.

• Tertiary structure is determined by a variety of interactions (bond formation) among R groups and between R groups and the polypeptide backbone.a. The weak interactions include: Hydrogen bonds among polar side chains Ionic bonds between

charged R groups ( basic and acidic amino acids)

Hydrophobic interactions among hydrophobic ( non polar) R groups.

b. Strong covalent bonds include disulfide bridges, that form between the sulfhydryl groups (SH) of cysteine monomers, stabilize the structure.

• Quaternary structure: results from the aggregation (combination) of two or more polypeptide subunits held together by non-covalent interaction like H-bonds, ionic or hydrophobic interactions.

• Examples on protein having quaternary structure:– Collagen is a fibrous protein of three polypeptides (trimeric) that are

supercoiled like a rope.•This provides the structural strength for their role in connective tissue.

– Hemoglobin is a globular protein with four polypeptide chains (tetrameric)

– Insulin : two polypeptide chains (dimeric)

Classification of proteins

I- Simple proteins:i.e. on hydrolysis gives only amino acids

Examples: 1- Albumin and globulins: present in egg, milk and bloodThey are proteins of high biological value i.e. contain all essential amino acids and easily digested. Types of globulins:

α1 globulin: e.g. antitrypsin: see laterα2 globulin: e.g. hepatoglobin: protein that binds hemoglobin to prevent its excretion by the

kidneyβ-globulin: e.g. transferrin: protein that transport ironγ-globulins = Immunoglobulins (antibodies) : responsible for immunity.

2- Globins (Histones): They are basic proteins rich in histidine amino acid. They are present in : a - combined with DNA b - combined with heme to form hemoglobin of RBCs.

3- Gliadines are the proteins present in cereals.

4- Scleroproteins: They are structural proteins, not digested. include: keratin, collagen and elastin.a- α-keratin: protein found in hair, nails, enamel of teeth and outer layer of skin. • It is α-helical polypeptide chain, rich in cysteine and hydrophobic (non polar) amino acids so

it is water insoluble.

b- collagens: protein of connective tissues found in bone, teeth, cartilage, tendons, skin and blood vessels.

• Collagen may be present as gel e.g. in extracellular matrix or in vitreous humor of the eye.

• Collagens are the most important protein in mammals. They form about 30% of total body proteins.

• There are more than 20 types of collagens, the most common type is collagen I which constitutes about 90% of cell collagens.

• Structure of collagen: three helical polypeptide chains (trimeric) twisted around each other forming triplet-helix molecule.

• ⅓ of structure is glycine, 10% proline, 10% hydroxyproline and 1% hydroxylysine. Glycine is found in every third position of the chain. The repeating sequence –Gly-X-Y-, where X is frequently proline and Y is often hydroxyproline and can be hydroxylysine.

Solubility: collagen is insoluble in all solvents and not digested.

• When collagen is heated with water or dil. HCl it will be converted into gelatin which is soluble , digestible and used as diet ( as jelly). Gelatin is classified as derived protein.

Some collagen diseases:

1- Scurvy: disease due to deficiency of vitamin C which is important coenzyme for conversion of proline into hydroxyproline and lysine into hydroxylysine. Thus, synthesis of collagen is decreased leading to abnormal bone development, bleeding, loosing of teeth and swollen gum.

2- Osteogenesis Imperfecta (OI): Inherited disease resulting from genetic deficiency or mutation in gene that synthesizes collagen type I leading to abnormal bone formation in babies and frequent bone fracture in children. It may be lethal.

C- Elastin: present in walls of large blood vessels (such as aorta). It is very important in lungs, elastic ligaments, skin, cartilage, ..

It is elastic fiber that can be stretched to several times as its normal length.

Structure: composed of 4 polypeptide chains (tetramer), similar to collagen being having 33% glycine and rich in proline but in that it has low hydroxyproline and absence of hydroxy lysine.

Emphysema: is a chronic obstructive lung disease (obstruction of air ways) resulting from deficiency of α1-antitrypsin particularly in cigarette smokers.

Role of α1-antitrypsin: Elastin is a lung protein. Smoke stimulate enzyme called elastase to be secreted form neutrophils (in lung). Elastase cause destruction of elastin of lung.

α1-antitrypsin is an enzyme (secreted from liver) and inhibit elastase and prevent destruction of elastin. So deficiency of α1-antitrypsin especially in smokers leads to degradation of lung and destruction of lung ( loss of elasticity of lung, a disease called emphysema.

Conjugated proteins

i.e. On hydrolysis, give protein part and non protein part and subclassified into:

1- Phosphoproteins: These are proteins conjugated with phosphate group. Phosphorus is attached to oh group of serine or threonine. e.g. Casein of milk and vitellin of yolk.

2- Lipoproteins: These are proteins conjugated with lipids. Functions: a- help lipids to transport in blood b- Enter in cell membrane structure helping lipid soluble substances to pass through cell membranes.

3- Glycoproteins: proteins conjugated with sugar (carbohydrate)e.g. – Mucin - Some hormones such as erythropoeitin - present in cell membrane structure - blood groups.

4- Nucleoproteins: These are basic proteins ( e.g. histones) conjugated with nucleic acid (DNA or RNA).e.g. a- chromosomes: are proteins conjugated with DNA b- Ribosomes: are proteins conjugated with RNA

5- Metalloproteins: These are proteins conjugated with metal like iron, copper, zinc, ……

a- Iron-containing proteins: Iron may present in heme such as in - hemoglobin (Hb) - myoglobin ( protein of skeletal muscles and cardiacmuscle), - cytochromes, - catalase, peroxidases (destroy H2O2) - tryptophan pyrrolase (desrtroy indole ring of tryptophan).

Iron may be present in free state ( not in heme) as in:- Ferritin: Main store of iron in the body. ferritin is present in liver, spleen and bone

marrow.- Hemosidrin: another iron store.- Transferrin: is the iron carrier protein in plasma.

b- Copper containing proteins: e.g. - Ceruloplasmin which oxidizes ferrous ions into ferric ions. - Oxidase enzymes such as cytochrome oxidase. c- Zn containing proteins: e.g. Insulin and carbonic anhydrased- Mg containing proteins:e.g. Kinases and phosphatases. 6-Chromoproteins: These are proteins conjugated with pigment. e.g.- All proteins containing heme (Hb, myoglobin, ………..)- Melanoprotein:e.g proteins of hair or iris which contain melanin.

Derived proteins

Produced from hydrolysis of simple proteins.e.g. - Gelatin: from hydrolysis of collagen - Peptone: from hydrolysis of albumin