UNIVERSITÄTSMEDIZIN

NEUMARKT A. M. https://edu.umch.de
www.umfst.ro

CAMPUS HAMBURG PRESENTER: 2022 SEPTEMBER, 27th

Lecturer KOVACS Zsolt
AMINOACIDS, PEPTIDES, PROTEINS
 Contents
1. Aminoacids
1.1. Clasification of aminoacids
Aminoacids, 1.2. The biological role of aminoacids
1.3. Physical properties of aminoacids
peptides, proteins 1.4. Non proteinogenic amino acids
2. Peptide
2.1. Peptide of biological importance
3. Proteins
3.1. Proteins structure
3.1.1. Primary structure
3.1.2. Secondary structure
3.1.3. Tertiary structure
3.1.4. Quaternary structure
Lecture 1 3.2. Clasification of proteins
3.2.1. Simple proteins
Assoc. Prof. Amelia Tero-Vescan 3.2.2. Heteroproteins
3.2.2.1. Glycoproteins
3.2.2.2. Lipoproteins

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 1. Aminoacids

• Definition - aminoacids are organic compounds with a mixed amino-carboxylic acid group

• These substances are also known as alpha-amino acids because, they have a primary amino group and a carboxylic acid
group substituent on the same carbon atom Cα (with the exception of proline)

• amino acids may contain other functional groups

• -OH in aliphatic or aromatic hydroxyamino acids,
α
• -SH in thioamino acids
• additional amino or carboxyl groups

General structure of an aminoacid

• There are also nonproteinogenic amino acids with an extremely important role (beta alanine, creatine, carnitine, etc.).

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 1.1. Clasification of aminoacids

❶ by the possibility / impossibility of being synthesized in the body :

❽Esential aminoacids ❷Semiesential

❿Not essential
Val, Leu, Met, Lys, Ile, aminoacids
aminoacids
Thr, Trp, Phe His, Arg

❷ by general chemical characteristics of their R groups:

a. Hydrophobic amino acids with nonpolar R groups: Ala, Val, Ile, Leu, Phe, Pro, Met, Trp;
b. Polar amino acids with neutral R groups but the charge is not evenly distributed: Ser, Tyr, Thr, Cys, Gln, Asn;
c. Positively charged amino acids with R groups that have a positive charge at physiological pH: Lys, His, Arg;
d. Negatively charged amino acids with R groups that have a negative charge at physiological pH: Asp, Glu.

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Hydrophobic amino acids with nonpolar R groups
Ala, Val, Ile, Leu, Phe, Pro, Met, Trp

Glycine, Gly, G Alanine, Ala, A Valine, Val, V Leucine, Leu, L Proline, Pro, P

Isoleucine, Ile, I Metionine, Met, M Triptophan, Trp, W

Phenilalanine, Phe, F

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Polar amino acids with neutral R groups but the charge is not evenly distributed
Ser, Thr, Tyr, Cys, Gln, Asn

Serine, Ser, S Threonine, Thr, T

Cysteine, Cys, C Glutamine, Gln, Q Tyrosine, Tyr, Y

Asparagine, Asn, N 6
Positively charged amino acids with R groups that have a positive charge at physiological pH
Lys, His, Arg

Lysine, Lys, K Arginine, Arg, R Histidine, His, H

Negatively charged amino acids with R groups that have a negative charge at physiological pH
Asp, Glu

Aspartic acid, Asp, D Glutamic acid, Glu, E

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1.2. The biological role of amino acids in the body is extremely complex:

a. the most important role of amino acids in the body is in protein synthesis (structural role);
b. the energy role is limited by the need to convert and / or remove ammonia (4.1 kcal /g);
c. catalytic role in the form of enzymes;
d. role in regulating osmotic pressure and acid-base balance;
e. transporting role - protein binding of endogenous (metabolite) or exogenous compounds allows their
distribution in different compartments;
f. the role of regulation - goes into the structure of hormones with peptide or protein structure.

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1.3. Physical properties of amino acids
- Aminoacids are amphoteric substances
- Amino acids in solution at neutral pH exist predominantly as dipolar ions (also called zwitterions ). In the dipolar
form, the amino group is protonated (-NH3 +) and the carboxyl group is deprotonated (-COO-).

zwitterion

-The ionization state of an amino acid varies with pH

Alkaline pH
As the pH is raised, the
carboxylic acid is the first group
+ + H2O to give up a proton

In acid solution (e.g., pH 1), the

amino group is protonated (-NH3 +)
and the carboxyl group is not
+ H3O + H2O dissociated (-COOH)
Acid pH
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 1.4. Non proteinogenic amino acids
In addition to the 20 amino acids that enter the structure of proteins, some are found to be free in tissues, as important
precursors or intermediates in metabolism.
β-alanine enters the structure Ornithine Orn and citrulline Cyt
Orn
of pantothenic acid, CoA-SH, participate as intermediates in the
anserine, carnosine. ureogenetic cycle.

Cyt
β-Ala Δ-Aminolevulinic acid (δ-ALA) is
Gamma-aminobutyric acid formed from succinyl-CoA and Gly
(GABA) is formed by enzymatic as an intermediate in porphyrin δ-ALA
decarboxylation of glutamic acid biosynthesis.
and is an inhibitory p-aminobenzoic acid (PABA) in the
neurotransmitter. structure of folic acids and is a PABA
growth factor for some
microorganisms.

GABA Creatine as creatine-phosphate is

an energy reservoir in muscle
tissue. Creatine
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2. Peptide
Definition: peptides are linear polymers formed by linking the alpha-carboxyl group of one aminoacid to the alpha-amino
group of another amino acid.
- This type of linkage is called a peptide bond or an amide bond
- The formation of a dipeptide from two amino acids is accompanied by the loss of a water molecule

+
-H2O
peptide bond
Amino Carboxyl
Glycine Alanine terminal residue terminal residue

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 Amino Carboxyl
terminal residue terminal residue

Tyr Gly Gly Phe Leu

• Pentapeptide Tyr-Gly-Gly-Phe-Leu is an opioid peptide that modulates the perception of pain

• The reverse pentapeptide, Leu-Phe-Gly-Gly-Tyr, is a different molecule and has no such effects.
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2.1. Peptide of biological importance

γ- glutamyl-cystenyl-glicine
highly concentrated in muscle and brain tissues acting as a buffer
Glutathione

Prevents cell damage caused by reactive

oxygen species such as free radicals,
peroxides, lipid peroxides, and heavy
metals.
Insulin - is a peptide hormone produced
by beta pancreatic cells. It is considered
to be the main anabolic hormone of the
body by regulating the metabolism of
carbohydrates, fats and proteins

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3. Proteins

Definition = complex macromolecules with a high degree of structural complexity

3.1 Proteins structure

3.1.1. It is given by the total number of amino acids, their nature and the order of binding in the polypeptide chain
Primary
Structure Ala – Glu – Ser – Gly – Asp - .........
Short !!!!
Peptide bond normal - It is an atypical amide bond
- The bond resonates between a
single bond and a double bond
- Allows the free rotation of the 2
atoms involved => cis-trans
isomerism
- Natural proteins are trans isomers
Long !!!!
normal
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 3.1.2.
Secondary In 1951, Linus Pauling and Robert Corey proposed two periodic structures called alpha helix and
Structure the beta pleated sheet

Alpha helices and beta pleated sheet are formed by hydrogen bonds between the peptide N- H
and C=O groups of amino acids that are near one another in the linear sequence

alpha helix beta pleated sheet 15

Alpha helices

• rodlike structure
• the a helix is stabilized by hydrogen bonds between the NH
and CO groups of the main chain
• the CO group of each amino acid forms a hydrogen bond
with the NH group of the amino acid that is situated four
residues ahead in the sequence
• There are 3.6 amino acid residues per turn of helix
• The screw sense of an a helix can be right-handed
(clockwise) or left-handed (counterclockwise) but right-
handed helices are energetically more favorable because
there is less steric clash between the side chains and the
backbone. Essentially all helices found in proteins are right-
handed.

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 • amino acids that disrupt the secondary structure: branch carbon chain aminoacids
(valine, threonine, isoleucine) because of steric clashes.
! • Serine, aspartate, asparagine because their side chains contain hydrogen-bond
donors or acceptors
• Proline because it lacks an NH group and because its ring structure do not fit into an a
helix.

The alpha -helical content of proteins ranges

widely, from none to almost 100%.

E.g.: about 75% of the residues in ferritin, a

protein that helps store iron, are in alpha helices

Ferritin structure17
Alpha-keratin, which is an essential component of wool, hair, and skin, consists
of two right-handed a helices intertwined to form a type of left-handed
superhelix called an -helical coiled coil

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Beta pleated sheet = Beta sheet
• The beta sheet is composed of two or more polypeptide chains called strands.

Beta strand

A beta sheet is formed by linking two or more beta strands lying next to one another through hydrogen bonds:

In opposite directions (antiparallel beta sheet) In the same direction (parallel beta sheet).

A B

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 The hydrogen-bonding scheme is slightly more complicated.
A For each amino acid, the NH group is hydrogen bonded to the
CO group of one amino acid on the adjacent strand, whereas
the CO group is hydrogen bonded to the NH group on the
amino acid two residues farther along the chain

antiparallel beta sheet

The NH group and the CO group of each amino acid are

hydrogen bonded to the CO group and the NH group of a
partner on the adjacent chain

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 it results from summing up all the interactions between the different radicals
3.1.3. Tertiary
Structure

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Myoglobin
• the oxygen storage protein in muscle,
• is a single polypeptide chain of 153 amino acids.
• The capacity of myoglobin to bind oxygen depends
on the presence of heme, a nonpolypeptide
prosthetic (helper) group
• About 70% of the main chain is folded into eight a
helices, and much of the rest of the chain forms
turns and loops between helices.

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 3.1.4. • Refers to proteins containing more than one polypeptide chain.
Quaternary • Each polypeptide chain in such a protein is called a subunit.
Structure • Quaternary structure refers to the spatial arrangement of subunits and the nature of their
interactions.

Human hemoglobin
Human hemoglobin the oxygen-carrying protein
in blood, consists of two subunits of one type (designated
alpha) and two subunits of another type (designated beta)

Protein No. of subunits

Lactate dehydrogenase 2
Myosin 2
Hemoglobin 4
Ceruloplasmin 8
Tobacco mosaic virus 2130
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3.2. Classification of proteins Globular proteins
• predominant in biological fluids
• E.g. albumin, globulin, antibodies, some hormones
SIMPLE • are generally soluble
consisting of amino acids
Fibril protein
• soluble fibrinogen, myosin, actin;
• insoluble collagen, elastin, keratin, fibroin.
Nucleoproteins - the prosthetic part = nucleic acids;

Chromoproteins - Prostethic part = porphyrinic: hemoglobin, myoglobin, cytochromes, catalase,

HETEROPROTEINS peroxidase,
- prosthetic part with flavinic structure: D-amino acid oxidase, succinate-DH

protein (apoprotein) + Glycoproteins – prostethic part = carbohydrate: gamma-globulin, ovoalbumin,

prosthetic group human plasma glycoproteins etc;

Lipoproteins – prosthetic part = lipid E.g. phosphoproteins

Metalloproteins – prosthetic part is a metal bonded directly to the apoprotein: ferritin (the
form of iron deposit), ceruloplasmin (the form of copper transport) etc

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3.2.1. SIMPLE PROTEINS

A. Globular proteins
• spherical or ellipsoidal in shape, watersoluble
• enzymes, hormones with protein structure and
plasma proteins

Albumin is water-soluble, Globulins have higher molecular

found especially in the blood weight, are not watersoluble
serum • include: milk lactoglobulin, egg Albumin
• it regulates colloid-osmotic ovoglobulin, serum globulins that
pressure of the plasma, carry lipids, carbohydrates,
• it transports the thyroid and hormones, different metabolites.
steroid hormones, bile salts,
ions, drugs.

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 Soluble • soluble fibrinogen, which in the process of
coagulation turns into insoluble fibrin
B. Fibrilar proteins
• myosin with major role in muscle contraction

Fibrinogen
• the most resistant proteins, insoluble in
Insoluble
water, acidic or basic solutions, they are not
hydrolyzed by the proteolytic enzymes.

Colagen (the most abundant protein

of mammals, the main fibrous component of
skin, bone, tendon, cartilage and teeth)
contains three helical polypeptide chains, each
nearly 1000 residues long.
Glycine appears at every third residue in
the amino acid sequence, and the sequence
glycine-proline-hydroxyproline
recurs frequently

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3.2.2. HETEROPROTEINS
3.2.2.1 Glycoproteins= carbohydrate group can be covalently attached to a protein to form a glycoprotein.
• 50% of the proteome consists of glycoproteins.
• three classes of glycoproteins

❶ Glycoproteins ❷ Proteoglycans
• In class, the protein constituent is the largest • The protein component is conjugated to a particular
component by weight. type of polysaccharide called a glycosaminoglycan
• a variety of biochemical roles: components of • Carbohydrates are the largest component
cell membranes (cell adhesion and the binding • Proteoglycans function as structural components and
of sperm to eggs). lubricants.

❸ Mucins or mucoproteins
• Are predominantly carbohydrate.
• N -Acetylgalactosamine is usually the
carbohydrate bound to the protein in mucins.
• Mucins, a key component of mucus, serve as
lubricants.

Each blood group is designated by the presence of one of the

! three different carbohydrates, termed A, B, or O, attached to
glycoproteins and glycolipids on the surfaces of red blood cells 27
❶ Glycoproteins
Sugars in glycoproteins are attached either to the amide nitrogen atom in the side chain of asparagine (termed an N- linkage)
or to the oxygen atom in the side chain of serine or threonine (termed an O- linkage)

serine or
asparagine threonine

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Erythropoietin (EPO) = glycoprotein hormone, present in the blood serum
that improved treatment for anemia, particularly that induced by cancer
chemotherapy

• secreted by the kidneys, stimulates the production of red blood cells

• 165 amino acids
• N -glycosylated at 3 Asn residues and O -glycosylated on a Ser residue
• mature EPO is 40% carbohydrate by weight,
• glycosylation inproves stability
• Unglycosylated protein has only about 10% of the bioactivity of the
glycosylated
• endurance athletes have used recombinant human EPO to increase the
red-blood-cell count and hence their oxygen-carrying capacity.
• Drug-testing laboratories are able to distinguish some forms of prohibited
EPO
human recombinant EPO from natural EPO in athletes by detecting
differences in their glycosylation patterns

Lance Armstrong
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❷ Proteoglycans = proteins attached to glycosaminoglycans (aprox 95% of the weight) so it resembles a polysaccharide
more than a protein
• lubricants, structural components in connective tissue
• The properties of proteoglycans are determined by the glycosaminoglycan component.
• many glycosaminoglycans contain a derivative of an amino sugar - glucosamine or galactosamine

Chondroitin 6-sulfate Keratan sulfate Heparin

Anticoagulant

Dermatan sulfate Hyaluronate

Major glycosaminoglycans 30
Proteoglycans in cartilage ! 2 importants components of cartilage: proteoglycan aggrecan + protein collagen
structure
Shock absorber Strength
• 2397 amino acids
• The protein has three
globular domainswhere
keratan sulfate and
chondroitin sulfate are
attached
• water is bound to the negative charges of glycosaminoglycans
and serves a cushion
• when pressure is exerted, as when the foot hits the ground
while walking, water is squeezed from the glycosaminoglycan,
cushioning the impact.
• When the pressure is released, the water rebinds.

• Osteoarthritis - water is lost from proteoglycan with aging

or the proteolytic degradation of aggrecan and collagen in
the cartilage. 31
❸ Mucins or mucoproteins
The protein component is extensively glycosylated at serine or
threonine residues by N -acetylgalactosamine

N -acetylgalactosamine

Mucins form large polymeric structures and are common in mucous

secretions (E.g. saliva)

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 3.2.2.2. Lipoproteins VLDL (very low density
lipoproteins) have very high
• prosthetic component = fatty acids, density small
triglycerides, lecithins, cephalins, • transport the triglycerides
cholesterol, fat-soluble vitamins. LDL (low density lipoprotein) synthesized in the liver to
• are part of membrane structure, or represents the cholesterol the extra hepatic tissues Chilomicrons have low
are found in plasma and have the role transportor for tissues density and large size
of transporting plasma lipids. • a risk factor in atherosclerosis • transport food lipids
• Although they have a high lipid
content (sometimes 90%), they are
still water soluble, which is why it is
admitted that the protein part is
located on the outside, and the lipid
part on the inside
• Lipoproteins are classified by density
(the higher the lipid content, the
lower the density)

HDL (high density lipoproteins) have high

density
• transport of cholesterol from tissues to
the liver where it is transformed 33