Transcript Биологическая химия

Biochemistry
Subject and Main Directions in
Biochemistry
Amino acids
Peptides
Proteins
Professor E.V. Lukasheva
Russian Peoples’ Friendship University
Medical Faculty
Department of Biochemistry
Professor:
Lukasheva
Elena Vasilievna,
Docror of biological
sciences
Лукашева Елена
Васильевна
Textbooks
1. Т.Т.Berezov, B.F. Korovkin «Biological Chemistry», М.,
Медицина, 1998.
2. «Биохимия» под ред. С.Е.Северина, М., Геотар-мед, 2003.
3. «Сборник тестов по биохимии», М., изд-во РУДН, 2004.
4. GARRETT&GRISHAM:
http://web.virginia.edu/Heidi/home.htm
Biochemistry Department is called by the name of
Academician Berezov Temirbolat Tembolatovich
(1924-2014)
Founder of the biochemistry
department, author of a
textbook on biochemistry for
medical students in Russia.
Scientific work was devoted to
the elaboration of anticancer
therapy based on enzymes of
microbial origin, which
catabolize amino acids:
L- asparaginase,
methionine-gamma-lyase,
L-lysine oxidase.
Biochemistry
investigates the molecular nature of life,
including:
1. The chemical nature of the substances that
make up living organisms.
2. Their transformation.
3. The relationship of these reactions to the activity
of cells, organs, tissues.
4. The ways of affecting the biochemical processes
in a living organism.
Plan
III- semester
IV- semester
Four colloquia
Rank
Three colloquia
Examination
Plan
1. On the stand of the Biochemical
Department
2. At the web site of Lukasheva E.V.:
РУДН
Учебный портал
Лукашева Елена Васильевна
History of Biochemistry (b/c)
B/c - a young science that has developed at
the turn of 19th - 20th centuries.
The term "biochemistry" was introduced by
Carl Neuberg in 1903.
BACKGROUND OF b/c – the development
of organic chemistry and the discovery
beginning the mid-18th century of large
amount of organic molecules in plants and
animals.
Important stages of biochemistry origin
are the synthesis of:
1828 - Urea (Wöhler*, Friedrich)
1845 - Acetic acid (A.Kolbe)
1854 - Fats (M.Bertlo)
1861 – Carbohydrates (Butlerov** A.M.)
* Wöhler for the first time synthesized an organic compound
from inorganic substances, thereby dealing a blow to the
widespread vitalistic doctrine of a so-called life-force.
** Butlerov – the author of the theory of chemical structure of
organic compounds. One of the streets nearby Russian
Peoples’ Friendship University is called by his name.
• Departments of Physiological Chemistry at
medical Faculties of Russian Universities
emerged in the late 19th century.
Almost all the achievements have been
made ​in biochemistry during 100 years !!!!!
• Monthly – more than 50 biochemical
journals are published and a lot of web
editions.
• The amount of information in biochemistry
increases exponentially.
Development of biochemistry in
the 20th century
20-ies. - The discovery of many viruses and bacterial
diseases
30-ies. - The science of nutrition, vitamins
(molecular basis of scurvy, beri-beri, pellagra)
40-50-ies. - Hunting for enzymes
(now known more 3000 enzymes )
60-70-ies. - Hunting for genes
Presently the main directions
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Genetic engineering
Biotechnololgy
Bioenergetics
Neurobiology (decoding brain activity)
Metabolism in bone
Our life is a continuous flow of
chemical reactions
1. Digestion.
2. Absorption of substances in the intestine
and their transport into cells.
3. Transformation of substances into CO2 and
H2O with the energy accumulation in the
form of ATP (catabolism).
4. Synthesis of proteins, carbohydrates, lipids,
hormones and other substances
(anabolism).
5. Muscle contraction.
6. Creation of the inter-membrane
potentials.
7. Chemical processes of foreign
substances (xenobiotics) neutralization.
Biochemical reactions determine not only
our health but also the vision of the world
• Final reception - the processes in the central nervous
system (poorly understood still) A wide area for
investigation.
• Smell, taste - special receptors bind to substances
and transmit a signal to the central nervous system.
• Vision is based on the cis-trans isomerization of
retinal and dissociation of rhodopsin (retinal complex
with the protein opsin)
Cвязь эмоционального состояния с уровнем некоторых метаболитов и гормонов
Эмоции
Изменение уровня вещества
Агрессивность
↑ серотонина
Чувство комфорта, уверенности в
себе
↑ глюкозы, NaCl, высших жирных кислот
Повышение умственных
способностей
↑ кофеина, мочевой кислоты
(структурные аналоги пуринов)
↑ фенамина (структурный аналог фенилаланина)
↑ глицина
Различные эмоции
пептиды сна, молодости…
Слабость, апатия
↓ тиреоидных гормонов
(недостаток иода)
Возбудимость,
страстность
↑ (умеренное) тиреоидных
гормонов
Невыдержанность, агрессивность,
невозможность сосредоточиться
↑ (быстрое и мощное) адреналина
Эмоциональность, влюбленность,
стремление к противоположному
полу
Половые гормоны
Our sex is determined by the concentration
of certain molecules
DNA, hormones and their receptors – the main
molecules responsible for manifestation of
sexual characteristics
The molecular logic of life
Differences of wildlife from inanimate
1. Living creatures are characterized by high structural
organization, both in space and in time.
2. Interaction of the metabolism and the environment. Extraction
of energy from the external environment and its transformation.
3. As well the decay and synthetic processes proceed in the body
constantly, intensively and simultaneously.
4. Тhe ability of the organisms to replicate.
5. The ability to self-regulate.
What was the starting point of life
evolution?
Friedrich Engels believed that "life - a way of existence of protein bodies“
It is hard to put any class of compounds in the first place
because of their functional importance:
Lipids form a membrane and allow to separate the living organism
from the environment. Academician Alexander Oparin in 1924
put forward the theory of the origin of life in the coacervate
drops.
Proteins are involved in the implementation of almost all functions
in body (hormones, enzymes, transport proteins ...)
Nucleic acids are important for the transmission and storage of
hereditary information…
Currently, the palm belongs to the RNA
• NA can be synthesized naturally in certain
conditions (lightning bolt) of simple
molecules.
In recent years it was found that NA can
slowly catalyze both the reaction of their
own synthesis and protein synthesis.
Biochemistry is in close contact with:
Molecular biology
Bioorganic chemistry
Pharmacology
Pharmaceutical Chemistry
Normal and pathological physiology
Microbiology
Dentistry
Etc.
Part II
Amino acids (AA)
– are low molecular weight compounds
containing simulteneously amino and carboxyl
group.
~ 300 AA have been discovered.
• It was found that all the variety of proteins
consists of approximately 20 amino acids,
which are involved in ribosomal synthesis and
called proteinogenic.
All AA are amphoteric electrolytes, i.e. they
may exhibit both acidic and basic properties
The carboxyl group is acidic, it dissociates into ions in
aqueous solution to give a proton and a negatively charged
group COO¯
NH2- group has a basic character, it can bind hydrogen
proton and become positively charged. In AA molecule
proton from the carboxyl group may be transferred to amino
group – forming the so called zwitter-ion. In solutions the
amino acids are in the form of zwitter-ions.
General properties of proteinogenic AA
1. They are α-amino acids, i.e. an amino
group is located in the alpha position relative
to the carboxyl group and the general formula
is:
H
R
C
C
NH2
OH
O
2. Belong to L-amino acids
All α-amino acids (except glycine) have an asymmetric carbon
atom, possessing four different substituents. So they may have
optical isomers.
Optical isomers are designated by Latin letters. L- (from Lat.
Louvus - left) and D- (from the Latin dexter - right).
COOH
COOH
C
R
R
C
H2N
H
H
NH2
Stereoisomers
(chiral isomers)
• All protein life on the earth is "left". There are
"exceptions", but they only prove the rule.
• It turns out that D-amino acids are extremely
rare, but still occur. For example, they are
present in the shell of anthrax (сибирская язва),
which is therefore not degraded by enzymes
which break the protein chain L-amino acids
(proteinases).
• D-AA are also found in some antibiotics and the
cell walls of a number of bacteria and fungi.
Letter symbols of amino acids
Letter
Amino
acid
Letter
Amino
acid
A
R
N
D
C
E
Q
G
H
I
Ala
Arg
Asn
Asp
Cys
Glu
Gln
Gly
His
Ile
L
K
M
F
P
S
T
W
Y
V
Leu
Lys
Met
Phe
Pro
Ser
Thr
Trp
Tyr
Val
AA classification
1. According to the chemical nature of
radical
а) aromatic (Phe, Tir, Tri)
b) branched (Val, Leu, Ile)
c) cyclic non aromatic (Pro, His)
d) sulphur-containing (Cys, Met)
2. According to the ability of groups
in radicals to the polarization or
dissociation
а) non-polar,
possessing in radical
no groups, which are
able to polarize or
dissociate:
glycine, alanine,
valine, leucine,
isoleucine,
phenylalanine,
methionine, proline,
tryptophan.
b) polar,
possessing in radical:
hydroxo–group –
serine, threonine,
tyrosine;
sulphhydryl group –
cysteine;
amide group –
asparagine or
glutamine.
c) charged,
possessing in radical
dissociating group:
(+) charged
lysine
arginine
histidine;
(-) charged
glutamate
aspartate.
3. According to the affinity of side
radicals to polar solvents, in
particular water
Hydrophilic
1. Polar
2. Charged (+)
and (-)
Hydrophobic
Non-polar
Ala, Leu, Phe, Trp,Ile,
Val, Pro
Amphiphilic Tyr Gly Met
4. According to the possibility of
their synthesis in the body
essential
nonessential
should be taken with
food
(are not synthesized
in the body)
are synthesized in the
body
Essential AA
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•
•
•
•
•
phenylalanine
lysine
arginine*
histidine*
methionine
tryptophan
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•
•
•
valine#
leucine#
isoleucine#
threonine
* partially synthesized AA
# - branched AA
Proteins and peptides
– polymeric molecules, consisting of amino acid
residues
Proteins are polypeptides with a molecular
mass greater than 5,000 g / mol.
Peptide bond
A resonance structure is invoked to explain the rigidity of the
peptide group. Optimal electron delocalization (π-bonding)
within the peptide group depends upon the planar
arrangement of these atoms. The partial double-bond
character of the peptide bond is reflected in the intermediate
length of the peptide bond relative to single and double
carbon-nitrogen bonds. The peptide bond typically has a
length of 1.32-1.33 Å (1 Å = 10−10 m), while the C–N bond in
amines is typically ~1.49 Å, and the C=N bond of an imine is
~1.27 Å.
Structural and functional diversity of proteins
In how many ways can a chain of 20 different amino
acids residues be collected?
Number of variants: 2 × 10 raise to power18.
But proteins have different polypeptide chain length and
the same amino acid may be included several times.
So, indeed, the variety of proteins may be tremendous.
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•
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Dipeptides1·2
Threepeptides 1 ·2 ·3 =6
Tetrapeptides1 ·2 ·3 ·4 = 24
Dekapeptides 3 628 800 10 AA), а из 20амк намного больше
Если белок имеет всего 100 аминокислот в длину, то может
существовать 20 в степени 100 вариантов его строения
Hydrolysis
• The peptide bonds are hydrolyzed in acidic or
alkaline conditions as well as under the influence
of certain enzymes, called proteinases
(proteases, peptidases). This yields a mixture of
peptides and amino acids.
• Study of the products of partial and complete
hydrolysis of peptides and proteins play is
important for the understanding of their structure.
Peptides
Direct synthesis from
amino acids catalyzed
by enzymes
Hydrolysis of proteins
(specific proteolysis)
Peptide hormones are formed
by the specific proteolysis of their peptide
precursors
Peptids
dithreetetraoligo- 10-15 AA
poly - big peptides
Proteins
М.М. ≥ 5 000
Have a spatial structure
In E.coli 3 000 proteins.
In man more than 50 000.
Proteomics – the study of
big number of proteins
simultaneously
Some information about peptides
• Among the peptides have a substance necessary for the body, and is
- extremely poisonous. Peptides are many enzymes, hormones
(substances that control activity of different cells).
For example, water metabolism in the body controls the nonapeptide
(9 amino acid residues vasopressin.
Insulin - a peptide controlling sugar metabolism consists of two
chains, one of which includes 21, and the other - 30 amino acid
residues.
The active principle of poison pale toadstool - dipeptides, snake
venoms also contain peptides.
Dipeptide aspartame - an artificial sweetener (200 times sweeter than
his)
There are natural polypeptides of 3000 times sweeter than sugar.