Download 01 Structure, properties and biological functions of proteins

Biochemistry - as science; Structure, properties and biological
functions of proteins. Methods of secretion and purification.
Peptides. Complex proteins, their biological role.
• Proteins are the most abundant substances in most
cells - from 10% to 20% of the cell’s mass.
• More than 70-80 % of dry weight of muscles, lungs,
kidneys, spleen; 57 % of dry weight of liver, 45 % of
dry weight of brain are proteins. The lowest proteins
constituting in bones and teeth (20 and 18 %
responding).
• Contents of chemical elements in proteins: carbon is
51-55 %, oxygen is 21-28 %, nitrogen is 15-18 %,
hydrogen is 6-7 %, sulfur is 0.3-2.5 %. Some
proteins contain phosphorus iron, zinc, copper and
other elements - (0.2-2%).
AMINO ACIDS
• An amino acid is an organic compound that
contains both an amino (–NН3) group and a
carboxyl (-СООН) group. The amino acids found
in proteins are always α-amino acids.
Reaction of amino acids
• Reaction with alcohols – esters formation:
• Reaction with ammonia – amides formation:
• Decarboxylation:
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Salts are formed:
Deamination
• oxidation deamination:
• hydrolitic deamination:
• intramolecular deamination:
• redaction deamination:
Classification of amino acids
• Nonpolar amino acids contain one amino group, one
carboxyl group, and a nonpolar side chain.
• Polar neutral amino acids contain one amino group,
one carboxyl group, and а side chain that is polar but
neutral.
• Polar acidic amino acids contain one amino group and
two carboxyl groups, the second carboxyl group being
part of the side chain. There are two polar acidic amino
acids: aspartic acid and glutamic acid.
• Polar basic amino acids contain two amino groups and
one carboxyl group, the second amino group being part
of the side chain. There are three polar basic amino
acids: lysine, arginine, and histidine.
Essential and non-essential amino acids
• All of the 20 amino acids are necessary constituents of
human protein. Adequate amounts of 11 of the 20 amino
acids can be synthesized from carbohydrates and lipids in
the body if а source of nitrogen is also available. Because
the human body is incapable of producing 9 of these 20
acids, these 9 amino acids, called essential amino acids,
must be obtained from food.
• The human body can synthesize small amounts of some
of the essential amino acids, but not enough to meet its
needs, especially in the case of growing children.
• The 9 essential amino acids for adults are histidine,
isoleucine, leucine, lysine, methionine, phenylalanine,
threonine, tryptophan, and valine. (In addition,
arginine is essential for children).
Peptide formation
• Two amino acids can react in а similar way - the carboxyl
group of one amino acid reacts with the amino group of the
other amino acid. The products are а molecule of water and
а molecule containing the two amino acids linked by an
amide bond.
Peptides
• Short to medium-sized chains of amino acids are
known as peptides. А peptide is а sequence of amino
acids, of up to 50 units, in which the amino acids are
joined together through amide (peptide) bonds. А
compound containing two amino acids joined by а
peptide bond is specifically called а dipeptide; three
amino acids in а chain constitute а tripeptide; and so
on. The name oligopeptide is loosely used to refer to
peptides with 10 to 20 amino acid residues and
polypeptide to larger peptides.
Proteins
• Proteins are polypeptides that contain more than
50 amino acid units. The dividing line between а
polypeptide and а protein is arbitrary. The
important point is that proteins are polymers
containing а large number of amino acid units
linked by peptide bonds. Polypeptides are shorter
chains of amino acids. Some proteins have
molecular masses in the millions. Some proteins
also contain more than one polypeptide chain.
Function of proteins
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Catalysis. Enzymes, the proteins that direct and accelerate thousands of
biochemical reactions
Structure. Some proteins function as structural materials that provide
protection and support.
Movement. Proteins are involved in all types of cell movement. For example,
actin, tubulin, and а variety of other proteins comprise the cytoskeleton.
Defense. А wide variety of proteins have а protective role. Examples found in
vertebrates include keratin, the protein found in skin cells that aids in
protecting the organism against mechanical and chemical injury. The bloodclotting proteins fibrinogen and thrombin prevent blood loss when blood
vessels are damaged. The immuno-globulins (or antibodies) are produced by
lymphocytes in response to the invasion of foreign organisms such as bacteria.
Regulation. The binding of а hormone molecule to its target cell results in
specific changes in cellular function. Examples of peptide hormones include
insulin and glucagon, which regulate blood glucose levels. Growth hormone
stimulates cell growth and division.
Transport. Many proteins function as carriers of molecules or ions across
membranes or between cells. Examples of membrane proteins include the Na+К+ ATPase and the glucose transporter. Other transport proteins include
hemoglobin, which carries O2 to the tissues from the lungs, and the
lipoproteins, which transport lipids from the liver and intestines to other organs
Primary structure of а protein
• The primary structure of а protein is the sequence of amino
acids present in its peptide chain or chains.
• The end with the free H3N+ group is called the N-terminal
end, and the end with the free СОО- group is called the Сterminal end.
Primary structure
Secondary
structure of а protein
• The secondary structure of а protein is the arrangement in
space of the atoms in the backbone of the protein. Three
major types of protein secondary structure are known; the
alpha helix, the beta pleated sheet, and the triple helix. The
major force responsible for all three types of secondary
structure is hydrogen bonding between а carbonyl oxygen
atom of а peptide linkage and the hydrogen atom of an amino
group (-NH) of another peptide linkage farther along the
backbone.
Secondary
structure
Alpha Helix
• The Alpha Helix The alpha helix (α-helix) structure resembles а
coiled helical spring, with the coil configuration maintained by
hydrogen bonds between N – Н and С= О groups of every fourth
amino acid
Beta pleated sheet
• The beta pleated sheet (β-pleated sheet) secondary
structure involves amino acid chains that are almost
completely extended.
Tertiary structure
The tertiary structure of а protein is the
overall three-dimensional shape that results
from the attractive forces between amino
acid side chains (R groups) that are widely
separated from each other within the chain.
There are four types of bonding interactions
between "side chains" including: hydrogen
bonding, salt bridges, disulfide bonds, and
non-polar hydrophobic interactions.
Tertiary structure
Interactions responsible for tertiary
structure
hydrogen bonds;
electrostatic attractions
(salt bridges);
covalent disulfide bonds;
hydrophobic attractions;
Electrostatic attractions (salt bridges),
Hydrogen bonds,
Quaternary structure
• Quaternary structure is the highest level of
protein organization. It is found only in proteins
that have structures involving two or more
polypeptide chains that are independent of each
other — that is, are not covalently bonded to each
other. These multichain proteins are often called
oligomeric proteins. The quaternary structure of а
protein involves the associations among the
separate chains in an oligomeric protein.
Hemoglobin
Globular and fibrous proteins
• On the basis of structural shape, proteins can be classified into
two major types: fibrous proteins and globular proteins.
• А fibrous protein is а protein that has а long, thin, fibrous
shape. Such proteins are made up of long rod-shaped or stringlike molecules that can intertwine with one another and form
strong fibers. They are water-insoluble and generally have
structural functions within the human body.
• А globular protein is а protein whose overall shape is roughly
spherical or globular. Globular proteins either dissolve in water
or form stable suspensions in water, which allows them to travel
through the blood and other body fluids to sites where their
activity is needed.
Simple and Conjugated Proteins
• Proteins are classified as either simple
proteins and conjugated proteins.
• А simple protein is made up entirely of
amino acid residues.
• А complex protein has other chemical
components in addition to amino acids.
These additional components, which may
be organic or inorganic, are called
prosthetic groups.
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Glycoproteins. Glycoproteins are proteins that contain carbohydrate. Proteins destined for an
extracellular location are characteristically glycoproteins. For example, fibronectin and proteoglycans are
important components of the extracellular matrix that surrounds the cells of most tissues in animals.
Immunoglobulin G molecules are the principal antibody species found circulating free in the blood
plasma. Many membrane proteins are glycosylated on their extracellular segments.
Lipoproteins. Blood plasma lipoproteins are prominent examples of the class of proteins conjugated
with lipid. The plasma lipoproteins function primarily in the transport of lipids to sites of active
membrane synthesis. Serum levels of low density lipoproteins (LDLs) are often used as a clinical index
of susceptibility to vascular disease.
Nucleoproteins. Nucleoprotein conjugates have many roles in the storage and transmission of genetic
information. Ribosomes are the sites of protein synthesis. Virus particles and even chromosomes are
protein-nucleic acid complexes.
Phosphoproteins. These proteins have phosphate groups esterified to the hydroxyls of serine,
threonine, or tyrosine residues. Casein, the major protein of milk, contains many phosphates and serves
to bring essential phosphorus to the growing infant. Many key steps in metabolism are regulated between
states of activity or inactivity, depending on the presence or absence of phosphate groups on proteins, as
we shall see in Chapter 15. Glycogen phosphorylase a is one well-studied example.
Metalloproteins. Metalloproteins are either metal storage forms, as in the case of ferritin, or enzymes
in which the metal atom participates in a catalytically important manner. We encounter many examples
throughout this book of the vital metabolic functions served by metalloenzymes.
Hemoproteins. These proteins are actually a subclass of metalloproteins because their prosthetic
group is heme, the name given to iron protoporphyrin IX (Figure 5.15). Because heme-containing
proteins enjoy so many prominent biological functions, they are considered a class by themselves.
Flavoproteins. Flavin is an essential substance for the activity of a number of important
oxidoreductases. We discuss the chemistry of flavin and its derivatives, FMN and FAD, in the chapter on
electron transport and oxidative phosphorylation