proteins: polymers of amino acids 20 different amino acids: many combinations proteins are made in...

Proteins: Polymers of Amino Acids

• 20 different amino acids: many combinations

• Proteins are made in the RIBOSOME

Amino Acid Chemistry

NH2 C

R1

CO

H

NH C

R2

COOH

H

NH2 C

R

COOH

H

amino acid

20 different types

Amino acid Polypeptide Protein

NH2 C

R1

COOH

H

NH2 C

R2

COOH

H

Amino Acid Chemistry

NH2 C

R

COOH

H

amino acid

The free amino and carboxylic acid groups have pKa’s

COOH COO-

pKa ~ 2.2

NH2NH3+

pKa ~ 9.4

At physiological pH, amino acids are zwitterions

+NH3 C

R

COO-

H

Amino Acid Chemistry

Note the axesAlso titratable

groups in side chain

Glycine Gly - G                                      

2.4 9.8

Alanine Ala - A                                          

2.4 9.9

Valine Val - V

2.2 9.7

Leucine Leu - L

2.3 9.7

Isoleucine

Ile - I

2.3 9.8

Amino Acids with Aliphatic R-Groups

pKa’s

Amino Acids with Polar R-GroupsNon-Aromatic Amino Acids with Hydroxyl R-Groups

Serine Ser - S                                                            

2.2 9.2 ~13

Threonine Thr - T

2.1 9.1 ~13

Amino Acids with Sulfur-Containing R-Groups

Cysteine Cys - C                                                           

1.9 10.8 8.3

Methionine

Met-M

2.1 9.3

Aspartic Acid Asp - D                                                                  

2.0 9.9 3.9

Asparagine Asn - N                                                                    

2.1 8.8

Glutamic Acid

Glu - E                                                                             

2.1 9.5 4.1

Glutamine Gln - Q                                                                                 

2.2 9.1

Basic Amino Acids

Arginine Arg - R

1.8 9.0 12.5

Lysine Lys - K                                                                              

2.2 9.2 10.8

Histidine

His - H                                                                  

1.8 9.2 6.0

Aromatic Amino Acids and Proline

Phenylalanine

Phe - F

                                                             2.2 9.2

Tyrosine Tyr - Y

                                                                        2.2 9.1 10.1

Tryptophan Trp-W

                                                                      2.4 9.4

Proline Pro - P                              

2.0 10.6

Hierarchy of Protein Structure

• 20 different amino acids: many combinations

• 8 essential

The order of amino acids: Protein sequencePrimary Structure

Local conformation, depends on sequenceSecondary Structure

Overall structure of the chain(s) in full 3DTertiary/Quaternary Structure

Binding Classification of Binding Classification of ProteinsProteins

Structural- other structural proteins

Receptors- regulatory proteins, transmitters

Toxins- receptors

Transport- O2/CO2, cholesterol, metals, sugars

Storage- metals, amino acids,

Enzymes- substrates, inhibitors, co-factors

Cell function- proteins, RNA, DNA, metals, ions

Immune response- foreign matter (antigens)

ClassificationEssential amino acids: There are amino acids that cannot be synthesized in the body.

They must be taken in diet.Their deficiency affects growth , health and proteins synthesis.

Half essential amino acids These amino acids are synthesized in the body in amount enough for adults , but not for growing children.

ArginineHistidine

Arginine is very popular among athletes and bodybuilders because it is required in muscle metabolism – maintaining the nitrogen balance, and helping with weight control

since it facilitates the increase of muscle mass, while reducing body

fat.

Non essential amino acidsThese are the rest of amino acids which are synthesized in the body , mostly from carbohydrates, in amount enough for adults and growing children.

Metabolic classificationKetogenic amino acids: which gives both ketone ketones bodies. Leucine is the only ketogenic amino acids.

People with liver and kidney problems can also benefit form L-Leucine

supplementation because it can enhance liver protein synthesis and improve

breathing ability and quality of sleep for those with kidney disorders.Finally, L-Leucine may lower blood

sugar levels and normalize and control insulin release and insulin function. Because of this, diabetics may find L-Leucine a helpful addition to their

disease management program.

Glucogenic and ketogenic amino acidsWhich give both ketone bodies and glucose are:

PhenylalanineTyrosineTryptopohanLysineIsoleucine

Functions of amino acidsBody peptides and proteins: E.g plasma proteins , tissue proteins, enzymes etc

Hormones: Some hormones are amino acids derivatives. E.g thyrosine and catecholamines.

Amines: Some amino acids give corresponding amines by decarboxylation e.g histidine gives histamine which is vasodilator.

Cont.Neurotransmitters: Some amino acids, glutamate acts as neurotransmitters.

Detoxification: Some amino acids are used detoxification reaction e.g glycine

Health and growth: Essential amino acids support growth in infants and maintain health in adults.

physical propertiesSolubility: Soluble in water, dilute acids , alkalies and ethanol.

Optical activity: Optically active because they contain asymetric carbon.

Melting point: High ionic forces. Tm 200˚C.

Chemical propertiesPeptide bond formation.Properties of R group.

ProteinsProteins are molecules having a very high molecular weight ,ranging from 5,000 to several million.

The term protein is applied to describe molecules greater than 100 a.a

Molecules contain less than 100 a.a are termed :larger polypeptides.

Functions

Enzymes :all enzymes are proteinsTransport : of small molecules and ions e.g

1. Hemoglobin is a carrier for oxygen.2. lipoproteins , are carriers of lipids.

Structural proteinsCell membrane : GlycoproteinsSkin and bones e.g collagen

Hormonal regulationSome hormones are protein in nature e.g insulin.

Cellular receptors that recognise hormones are proteins.

Defence mechanism Antibodies (immunoglobulins) are proteins in nature.

Keratin found in skin and tissues is proteins that act against mechanical and chemical injuries.

Cont.Blood clotting : coagulation factorStorage: Ferritin ,which is a storage form of iron.

Control of genetic expression: activator receptors and many regulators of genes are protein in nature.

Conformation of proteinsEvery protein in its native state has a 3-dimensional structure.(primary, secondary, and tertiary),which is known as conformation . Conformation is essential for the function of each protein. Any change in conformation may lead to disease.

Primary proteinsIt is a order (arrangement) of amino acids in the polypeptide chain.(chains).

Covalent bond.Free NH3 and CooH terminals.The arrangement of amino acids in each protein is determined by the genetic information present in DNA.

Secondary proteinsHydrogen bonds Two forms alpha and beta form.

Right-hand helix

Left-hand helix

Helix

Tertiary structureTwo types:Fibrous : which is an extended form e.g keratin ,collagen and elastin.

Globular proteins: which is a compact form and folding of polypeptide chain e.g myoglobin.

Quaternary structureMany proteins are composed of several polypeptide chain .Each polypeptide chain is called subunits.

E.g insulin : 2 subunitsLactate dehydrogenase enzyme :4 subunits

Globin of haemoglobin:4 subunits.

Denaturation of proteinsDef : protein denaturation mean unfolding and loss of secondary ,tertiary and quaternary structure.

1.denaturation does not affect primary structure i.e not accompained by hydrolysis of peptide bonds.

2. denaturation may be reversible( in rare cases)

Effect of protein denaturationLoss of biological activity : insulin looses its activity after denaturaion.

Denaturation proteins are often insoluble.

Denaturation protein are easily precipitated.

Denaturation factorHeatOrganic solventsDetergentMechanical mixingStrong acids and basesHeavy metals.EnzymesRepeated freezing and thawing

Classification of proteinsSimple proteins: On hydrolysis they give only amino acids.

Conjugated proteins: give amino acids and non proteins (prosthetic group).

Derived proteins: 1. primary derived proteins : denatured protein

2.secondary derived proteins: product of hydrolysis of simple and conjugated proteins.

Simple proteinsAlbumin and globulinScleroproteins : include keratin ,collagen ,elastin,reticulin.

Alpha keratinFound in hair ,nail , enamel of teeth ,and outer layer of skin.

Rich in cysteineInsoluble due to high content of hydrophobic amino acids

collagenPresent in skin ,bones , tendons, and blood vessels.

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

collagen diseasesScurvy; it is due to deficiency in a ascorbic acids (vitamin c).

Ascorbic acids acts as coenzyme in hydroxylation reaction of proline and lysine.

Symptoms: abnormal bone development ,bleeding , loosing of teeth and swollen gums.

Cont.Osteogenesis imperfecta:1. It is a genetic disorders lead to weak bones and skeletal deformities.

2. It is due to mutation in the gene that code for α –chain for collagen.

Ehlers-Danlos syndrome:Genetic disorder lead to connective tissues disease

Symptoms : stretchy skin and loosed joints.

Elastin It is a connective tissue proteins.Rubber –like, stretched several timesPresent in lungs , the walls of large blood vessels and elastic ligaments.

Conjugated proteinsOn hydrolysis ,they give protein part (apoproteins) and nonproteins part(prosthetic group)

phosphoproteinsThese are protein conjugated with phosphate group.

Phosphate group is attached to –OH group of serine (phosphoserine) or threonine(phosphothreonine) present in protein part. E.g

Caseine :one of the milk proteinVitellin: present in egg yolk.Phosphoenzyme: phoephorylation and dephosphorylation.

lippoproteinsThese are proteins conjugated with lipids

Plasma proteins and cell membrane.Helps water insoluble lipids to transport in blood

Helps water insoluble substance to pass through cell membrane .

Glycoproteins and proteoglycansThese are proteins conjugated with carbohydrates in varying amount .i.e 2 to 15 sugar units.e.g blood group, enzyme and mucin

Proteoglycans contain long unbranched chains of sugar units more than 50 units. E.g cell membrane

nucleoproteinsThese are proteins conjugated with nucleic acid (DNA or RNA ).

1. chromosomes: proteins conjugated with DNA .

2. Ribosomes; proteins conjugated with RNA.

MetalloproteinsProteins conjugated with metalsMettaloproteins containing iron: The iron may be in the form of heme or nonheme iron.

Ferritin : is the storage form of iron ,present in liver ,spleen, bone marrow and intestinal cells.

Transferrin. Is the iron carrier protein in the plasma.

Hemosiderin :iron toxicity (over dosage) as in case of repeated blood transfusion.