Biochemistry 1
Fall semester 2019/2020
Lecturer: Assist. Prof. Dr. Altijana Hromic-Jahjefendic
Laboratory assistant: MSc Jasmin Sutkovic
Contact Information
Office: A F1.7
Office hours:
Monday 08:00-11:00
Thursday 13:00-15:00
General information
Syllabus
2 quizes (5% each) – FIRST QUIZ 29.10.2019 !!!!
Lab tutorials (20%)
Mid term exam (30%)
Last semester week: review of all lectures and preparing for
final exam
BOOK
- -”Principles of Biochemistry”, Moran- Horton-Scrimgeour-Perry, 2012 Pearson, 5th edition
- -”Biochemistry” Voet &Voet, 4th edition, 2011
- b-ok.org
What is Biochemistry?
History and Development
How to study Biochemistry?
Biochemistry
Definition:
The science concerned with the chemical basis of life.
The science concerned with the various molecules that
occur in living cells and organisms and with their chemical
reaction.
Anything more than a superficial comprehension of life in
all its diverse manifestation -demands a knowledge of
biochemistry.
Aim: to describe and explain, in molecular terms, all chemical
processes of living cells
Structure-function
Metabolism and Regulation
Disease development and treatment
Significance:be essential to all life sciences as the common
knowledge
Genetics; Cell biology; Molecular biology
Physiology and Immunology
Pharmacology and Pharmacy
Toxicology; Pathology; Microbiology
Zoology and Botany
Students who acquire a sound knowledge of biochemistry
will be in a strong position to deal with two central concerns
of the health sciences:
(1) the understanding and maintenance of health
(2) the understanding and effective treatment of disease:
▪Causes of cancers
▪Molecular lesions causing various genetic diseases
▪Rational design of new drugs
What is the purpose of biochemistry?
Structure and function of cellular components
proteins, carbohydrates, lipids, nucleic acids and other biomolecules
Metabolism and Regulation
Gene expression and modulation
The cell
Life is based on a morphological unit known as the cell
Two basic types of cells are found in nature: Prokaryotes
and eukaryotes
Eukaryotes (Greek: eu, good or true + karyon, kernel or
nut) have a membrane-enclosed nucleus containing their DNA.
They can form multicellular organisms.
Prokaryotes (Greek: pro, before) lack this organelle.
Prokaryotes are unicellular (bacteria).
Prokaryotes
First described by Antoni van Leeuwenhoek in 1683
Simple anatomy
1-10 μm
Three basic shapes:
Spheroidal (cocci)
Rodlike (bacilli)
Helically coiled (spirilla)
Bounded by a 70 Å plasma membrane and a 30 to 250 Å
cell wall
Eukaryotes
10- 100 μm, i.e. 103 to 106 times the volume of a
prokaryotic cell
it is not the size, however, but the high degree of complexity
of eukaryotic cells that makes the difference
• Cell membrane & cell wall Cell membrane
• Nucleoid region contains the DNA Nucleus
• Contain ribosomes (no membrane) Cytoplasm with organelles
Characteristic Biomembranes and Organelles
Plasma Membrane-Cell’s defining boundary. Providing a
barrier and containing transport and signaling systems.
Nucleus –Cell’s information center. Double membrane
surrounding the chromosomes and the nucleolus. The place
where almost all DNA replication and RNA synthesis occur.
Mitochondria-the power generators Mitochondria (Greek:
mitos-thread; chondros-granule). Functions in energy production
through metabolism.Contains its own DNA.
Characteristic Biomembranes and Organelles
Rough endoplasmic reticulum (RER). Covered with
ribosomes (causing the "rough" appearance) which are in the
process of synthesizing proteins for secretion or localization
in membranes.
•Ribosomes- Protein and RNA complex responsible for protein
synthesis
Smooth endoplasmic reticulum (SER) - A site for synthesis
and metabolism of lipids.
Golgi apparatus -process and package the macromolecules. Vesicles carry materials from the RER to the Golgi apparatus. Vesicles move between the stacks while the proteins are "processed" to a mature form.
Lysosomes-contain digestive enzyme. Is responsible for degrading proteins and membranes in the cell.
Cytoplasm - enclosed by the plasma membrane, liquid portion called cytosol and it houses the membranous organelles.
Biomolecules
biomolecules are building blocks of cells.
Animal and plant cells contain approximately 10,000 kinds of
biomolecules.
Water constitutes 50-95% of cells content by weight.
Ions like Na+, K+ and Ca2+may account for another 1%.
Almost all other kinds of biomolecules are organic (C, H, N,
O, P, S).
Organic compounds are compounds composed primarily of a
carbon skeleton.
Carbon
Carbon is more abundant in living organisms than it is in the
rest of the universe.
What makes Carbon Special?
ability of Carbon atoms to bond together to form long chains
and rings.
Biomolecules are compounds of carbon with a
variety of functional groups
Biochemistry - the lowest level of
complexity
Major building blocks are:
1. Proteins (Greek: proteios, of first importance)
2. Nucleic acids
3. Polysaccharides (Greek: sakcharon, sugar)
4. Lipids (Greek: lipos, fat)
The first three categories are complex polymers made of
smaller building blocks: amino acids, nucleotides and
monosaccharides
The information for the generation of such complex structures is encoded in
nucleic acids.
The flow of this information is regulated in a complex fashion.
The entire process is fueled by metabolic processes that generate energy from
organic energy sources and use this energy to synthesize complex molecules.
Metabolism Metabolism has been traditionally divided into two major
categories:
Catabolism - break down of nutrients and cell constituents to produce energy (ATP) and/or reuse for biosynthesis
Anabolism - biosynthetic pathways to generate the biomolecules required; the energy for biosynthesis is derived mostly from catabolic reactions (i.e. ATP).
Thus catabolism and anabolism are linked by the reciprocal interconversion of the „energy currency“ ATP.
Polymers and Monomers
Each of these types of molecules are polymers that are
assembled from single units called monomers.
Each type of macromolecule is an assemblage of a different
type of monomer.
How do monomers form polymers?
In condensation
reactions (also called
dehydration synthesis), a
molecule of water is
removed from two
monomers as they are
connected together.
Chemical composition of a healthy
person (65 kg)
Constituent Percent (%) Weight (kg)
Water 61.6 40
Protein 17.0 11
Lipid 13.8 9
Carbohydrate 1.5 1
Minerals 6.1 4
The beginning of biochemistry
biochemical processes are ubiquitous among living
organisms, it was the study of one particular process which
led to the discovery of biochemical principles:
ALCOHOLIC FERMENTATION
Fermentation was discovered at the start of the neolithic age around 10000 years
ago with the start of settlements and agriculture (confirmed for 6000 years).
Transformation of a juice of crushed grapes to a gift of euphoria.
Fermentation is also accompanied by the emergence of bubbles, production of heat
and the occurrence of a fine, cloudy suspension that eventually settles to the bottom
of the fermentation vats („yeast“)
The Vital Force - Aristotle Aristotle’s teleology:
Every living thing has a natural end or goal toward which it tends. The acorn’s natural tendency, for example, is to become an oak tree and a warrior’s natural goal is to become a hero.
Applying this teleological view to fermentation, grape juice can be regarded as an immature form of wine, and the process of fermentation is then the maturation of grape juice to wine (its final destiny).
What causes this inherent tendency?
In Aristotle’s view these maturation processes are under the control of inner driving forces, called vital force, lat. vis visa. Although the vital force is undefined in material terms, it is a real part of the organism endowing it with life. Indeed, the basic distinction between the animate and inorganic world is the very existence of the vital force (vitalism).
Alchemists identify alcohol as the product of fermentation
In Greek chemistry the world was made up of four fundamental substances: Earth, Air, Fire and Water. In addition to these physical elements, philosphocial considerations have led to the proposal of a fifth element, called quinta essentia or quintessence which reflects the vital force in animate things. This essence was thought to have a volatile character and hence alchemists in the Middle Ages have attempted to capture it using distillation. By the end of the 12th century distillation had become efficient enough to recover the vapors released from various heated substances. It became apparent that the distillation of grape juice and for example wine produced different vapors, in the latter case this vapor could be condensed to a burning liquid (aqua ardens). Hence it became clear that fermentation was not just a maturation but the formation of an entirely different new substance. We now know that this „spirit“ of wine or other alcoholic fermentation products is ethanol.
Antoine Lavoisier (1734-1794) One of the founders of modern
chemistry
Lavoisier’s two fundamental laws:
1. Substances undergoing a reaction
combine (or break apart) in specific
quantitative amounts - the law of
combining ratios.
2. The amount of matter present at the
beginning of a reaction is equal to
the amount of matter present at the
end - the law of the
conservation of mass.
2H2 + O2 -> 2H2O
2 + 1 -> 2 (combining ratio)
4H + 2O -> 4H + 2O (conservation of matter)
A unifying approach to the organic and
inorganic world Lavoisier proposed: fermentation was a chemical reaction in which
the sugar of the starting grape juice was converted into the ethanol of the finished wine.
In his experiments, he used sugar (instead of the grape juice), water and a small amount of yeast taken from a previous fermentation.
Comparison of the carbon present in the sugar and in the products (ethanol and carbon dioxide) revealed the conservation of mass, i.e. established that the laws of the inorganic world are applicable to the organic world as well.
By the end of the 18th century the inorganic and organic world were reunited in obeying the same rules.
The question of what caused the chemical transformation was unsolved.
The role of yeast in fermentation
Liebig’s theory:
The vibrational impact of decomposing yeast leads to the
disruption of the sugar atoms
-> Yielding ethanol and carbon dioxide as products.
This view was widely accepted among contemporary
chemists.
Opposing views: Theodor Schwann (1810-1882) & Charles Cagniard-Latour
(1777-1859):
• Yeast is a living organism
• Decomposition of sugar to ethanol and carbon dioxide is directly linked to the growth of yeast
• The „force“ that drives fermentation derives from a living organism as a result of its growth
ideas were rejected by most chemists at that time as an unwarranted intrusion of biology into the higher domain of chemistry. Basically, the idea of yeast as a living organism was totally dismissed
Pasteur on fermentation
A series of unsuccessful fermentations in the wine industry in
1856, prompted Pasteur to investigate the differences in the
sediments obtained from a normal and an unsuccessful
fermentation mixture
normal: yeast unsuccessful: bacteria
Seeding experiments
• Support for Schwann’s
and Cagniard-Latour’ s
that fermentation was
connected
with a living organism
Fermentation outside the living cell Eventually the stage was set for the final synthesis:
The Buchner brothers, a microbiologist and a chemist, developed a procedure to obtain a cell-free yeast extract by using a hydraulic press to generate a cell extract.
To preserve this extract they added 40% sucrose to it and observed bubbles some minutes later. This process sometimes continued for days and they could demonstrate that ca. 3% ethanol was produced during this fermentation.
This led to the demise of Pasteur’s concept of „higher and lesser“ processes and to the general acceptance of the idea of biological catalysis.
„The enzyme theory of life“
The discovery of zymase
Buchners called the active ferment isolated from yeast cells,
marked the beginning of biochemistry as an exact science
which „predicted that all cellular reactions would be
found to be controlled by specific enzymes“.
Although the Buchners believed that zymase was a single
entity, later on chemical events known as „metabolic
pathways“ were discovered
The discovery of the first amino acids
Liebig noticed that acid treatment resulted in the release of
smaller compounds which he could identify and obtain exact
formulars for: leucine, C6H13O2N and tyrosine
C9H11O3N (Greek: tyros, cheese)
Leucine and tyrosine were not the first amino acids
discovered!
A substance that was found to crystallize from extracts of
asparagus (especially when grown in the dark) was called
asparagine and turned out to be an amino acid
The polypeptide chain The current list of 20 amino
acids was eventually completed in 1935.
Franz Hofmeister and Emil Fischer had proposed the first clear theory of protein structure
they proposed that the protein is a chain of amino acids joined together by bonds between the regularly repeating amino and carboxyl groups.
The resulting chain, or polymer of linked amino acids, was termed a polypeptide chain.
Later on many experiments and discoveries regarding
proteins/enzymes
Structure determinations
Enzyme catalysis etc.
History and development of
Biochemistry
1903, Neuberg(German): “Biochemistry”
“Chemistry of Life”
Life possesses the properties of replication, catalysis and
mutability
Biochemistry is the study of life on the molecular level
Two important breaktroughts
(1) Discovery of the role of enzymes as catalysts
(2) Identification of nucleic acids as information
molecules
One gene one protein theory
DNA > RNA > Protein
Historic events
In 1937, Krebs for the discovery of the Citric Acid
Cycle-won the Nobel Prize in Physiology or
Medicine in 1953
In 1953, Watson & Crick for the discovery of the
“DNA Double Helix” -won the Nobel Prize in
Physiology or Medicine in 1962
Historic events In 1956. Sanger for the determination of insulin sequence-
won the Nobel Prize in Physiology or Medicine.
In 1980.Sanger & Gilbert for Sequencing of DNA-won the Nobel Prize in Chemistry.
In1993.KaryB. Mullis for invention of PCR method -won the Nobel Prize in Chemistry.
In 2016.-The Nobel Prize in Chemistry 2016 was awarded to Jean-Pierre Sauvage, Sir J. Fraser Stoddart and Bernard L. Feringa for their design and production of molecular machines. They have developed molecules with controllable movements, which can perform a task when energy is added
Historic events
The Nobel Prize in Chemistry 2018 was divided:
-one half awarded to Frances H. Arnold "for the directed
evolution of enzymes“
-the other half jointly to George P. Smith and Sir Gregory P.
Winter "for the phage display of peptides and
antibodies."
Historic events
Human Genome Project
Completed in 2003
Most complex project in the modern science
Summary
The cell
Eukaryotes vs Prokaryotes
Monomers vs polymers
Metabolism
Historic development of biochemistry
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