Transcript topic 1 - UMK CARNIVORES 3

BIOCHEMISTRY
DVT 1094
• NOR FADHILAH KAMARUZZAMAN
• B.Sc Biochemistry (UKM)
• M.Sc Molecular Medicine (USM)
1
Why study biochemistry?
“Often, the medical student will cringe
at the ‘drudgery’ of the basic science
courses and see little connection
between a field such as biochemistry
and clinical problems.
Clinicians, however, often wish they
knew more about the basic sciences,
because it is through the science that
we can begin to understand the
complexities of the human/animal
body and thus have rational methods
of diagnosis and treatment”.
2
Six key questions
1. What is the most likely biochemical mechanism for the disease causing
the patient’s symptom or physical examination finding?
2. Which biochemical marker will be affected by treating a certain disease,
and why?
3. Looking at graphical data, what is the most likely biochemical explanation
for the results?
4. Based on the deoxyribonucleic acid (DNA) sequence, what is the most
likely amino acid or protein result, and how will it be manifest in a clinical
setting?
5. What hormone–receptor interaction is likely?
6. How does the presence or absence of enzyme activity affect the
biochemical (molecular) conditions, and how does that in turn affect the
patient’s symptoms?
3
Biochemistry and The Organization
of Cells
4
What is Life Made of?
• Physical and Chemical sciences alone may not
completely explain the nature of life, but they
at least provide the essential framework for
such an explanation.
• All students of life science must have a
fundamental understanding of organic
chemistry and biochemistry.
5
Organic Chemistry
• Organic chemistry is the study of Carbon
compounds.
• Organic compounds are compounds
composed primarily of a Carbon skeleton.
• All living things are composed of organic
compounds.
6
Organic Chemistry
• What makes Carbon Special? Why is Carbon
so different from all the other elements on the
periodic table?
• The answer derives from the ability of Carbon
atoms to bond together to form long chains
and rings.
7
Organic Chemistry
8
Organic Chemistry
Carbon can covalently bond with up to
four other atoms.
9
Carbon can form immensely diverse
compounds, from simple to complex.
Methane with 1 Carbon
atom
DNA with tens of Billions of
Carbon atoms
10
How did living things originate?
11
12
Six level of structural organization that make one
organism
Chemical
organelle
tissues
organ
sytem
organism
• Atoms combine to form molecule
• All cells of organism contain structure that build up the
cell
• consist of group of similar cells that have common
function
• A structure that is composed of two major tissue types
and perform a specific function
• A group of organs that cooperate to accomplish a
common purpose
• Represent the highest level of structural organization
13
14
Variables
Biochemistry
• Science concerned with the chemical basis of
life
• Science concerned with the chemical
constituents of living cells and with the
reactions and process they undergo
15
Biochemistry
• Biochemistry is the application of chemistry to the study of
biological processes at the cellular and molecular level
• A special branch of organic chemistry that deals with matter
inside the living cells called protoplasm
• Protoplasm - is the living contents of a cell that is surrounded
by a plasma membrane. It is a general term of the Cytoplasm .
• Protoplasm is composed of a mixture of small molecules such
as ions, amino acids, monosaccharides and water,
and macromolecules such as nucleic
acids, proteins, lipids and polysaccharides.
16
How does biochemistry describe life processes?
• Living organisms are complex and universe
• Nevertheless, they still share the common element for survival
– biomolecules
• Biochemistry is a field that study the molecular nature of life
processes.
• Complete understanding at the molecular level of all the
chemical processes associated in living cells
• To describe and explain in molecular term all molecular process
of living cells
• Important application to medically related field- an
understanding of health and disease at the molecular level
leads to more effective treatment of illness of many kinds.
17
How much do you need
to know for this course?
1. You need to know the structure of organic
molecules important to major biological processes
2. You will be expected to learn the biochemical
processes of major cell functions
3. You will be expected to understand the clinical
correlation for the biochemical processes
18
Primary Organic Compounds
You are expected to
learn the structure
and functions of
these organic
compounds:
1.
2.
3.
4.
Carbohydrates
Lipids
Proteins
Nucleic Acids
19
Biochemistry
Study of
Composed of
Biomolecules
Living organisms
Classified as
need
Can be
Kingdoms
Nutrients
Determined by
provide
Complex molecules
Needed
to form
Simple molecules
Polysaccharides
form
Carbohydrates
Polynucleotides
form
Nucleotides
Proteins
form
Lipids
Energy
Morphology
Cells
Amino acids
Others
Eukaryotic
Components of
Prokaryotic
are
are
Complex cells
Simple cells
Enclosed by
Membranes
Organelles
Nuclear
bound DNA
Cytoplasm
DNA
20
Knowledge of biochemistry essential
to all life science
• Physiology
• Immunology
• Pathology
• Microbiology
21
CELLS AND
CELLULAR
COMPARTMENTS
22
Cells
• Basic building blocks of life
• Smallest living unit of an organism
• Grow, reproduce, use energy, adapt, respond to their
environment
• Many cannot be seen with the naked eye
• A cell may be an entire organism or it may be one of billions of
cells that make up the organism
• Basis Types of Cells
23
24
The Biggest Biological Distinction;
Prokaryote and Eukaryotes
25
The cell
• Prokaryote – earliest cells that evolve, simple,
minimum apparatus necessary for life
processes – e.g. bacteria, cyanobacteria
• Eukaryote – more complex organisms – e.g.
yeast, animal, plants, etc
26
Task 1: State the comparison of
prokaryote and eukaryote
27
Task 2: List all organelles and their
functions
28
Task 3: Discuss animal related disease
that is due to the ineffective function
of organelles
29
Biochemical energetics
• Source of energy in life processes
• Energy is needed to synthesis large molecules
and perform other reactions in the cell
30
Measuring energy changes in biochemistry
Reaction that take places as many part of
biochemical processes – hydrolysis of the
compound adenosine triphosphate (ATP)
31
• This reaction release energy- allow energy
requiring reaction to proceed
32
Molecules
Made of
have
Atoms
Physical
characteristics
Most abundant is
Held together by
H20
Can be
Chemical forces
Also contains
Polar
is
Covalent
H30+
Electrostatic
Non Polar
OHUsually
e.g
Stabilized
Attractions
by
-log conc. is
-log conc. is
Hydrophilic
e.g
Hydrophobic
pOH
•Van der Waals forces
•Hydrogen bonds
•Dipole-dipole
pH
Can be
maintained by
Buffer
Scale is
Theory is
Composed of
Handerson Hasselbach
equation
where
Conjugate
acid/base
pair
1 to 14
Studied by
Titration
Which
dissociates near
Plotted
as
↓ pH is
↑pH is
Acidic
Alkaline
curve
pH=pK when [A-]= [HA]
pK
is
indicates
Buffer
region
Equivalence
points
33
CELLULAR ENVIRONMENT:
WATER AND SOLUTES
34
Small organic molecules:
Carbohydrates, amino
acids, lipids, nucleotide,
peptides
H20
Chemical
Component of
Biological Cells
Macromolecules:
Protein,
polysaccharides,
nucleic acid
Inorganic ions:
Na+, K+, Cl-, S042-,
HC03-, Ca2+, Mg2+,
etc
35
WATER
36
Water
• Aqueous (water) solution are crucial for the chemical
reactions of living things
• Water is a polar compound
• Polarity – uneven pattern of electrical charge in molecules
37
Role of water as solvent
• Transport of nutrients, e.g. glucose and amino
acids in blood
• Removal of excretory products, e.g. ammonia,
urea
• Secretion of substances, e.g. hormones,
digestive juices
38
Water as universal solvent
• The polar structure makes water a very effective
solvent for other polar substances
e.g. sugar, protein, and ionic compound
• Ionic compound in water tend to dissociate into
free ions for other chemical reaction (dissolved
ionic compounds are in all aqueous solutions for
living things and are critical to normal operation
of body/cell system)
(e.g. Na+ and Cl- ions are vital to nerve and
muscle cell function)
39
Polarity of Water
• In a water molecule two hydrogen atoms
form single polar covalent bonds with an
oxygen atom. Gives water more structure
than other liquids
– Because oxygen is more electronegative, the
region around oxygen has a partial negative
charge.
– The region near the two hydrogen atoms has a
partial positive charge.
• A water molecule is a polar molecule with
opposite ends of the molecule with opposite
charges.
40
• Water has a variety of unusual properties
because of attractions between these polar
molecules.
– The slightly negative regions of one molecule are
attracted to the slightly positive regions of nearby
molecules, forming a hydrogen bond.
– Each water molecule
can form hydrogen
bonds with up to
four neighbors.
Fig. 3.1
Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings
41
HYDROGEN BONDS
• Hold water molecules
together
• Each water molecule can
form a maximum of 4
hydrogen bonds
• The hydrogen bonds
joining water molecules
are weak, about 1/20th as
strong as covalent bonds.
• They form, break, and
reform with great
frequency
• Extraordinary Properties that
are a result of hydrogen
bonds.
–
–
–
–
–
Cohesive behavior
Resists changes in temperature
High heat of vaporization
Expands when it freezes
Versatile solvent
42
HYDROGEN BONDS
• Alcohol, amines, carboxylic acid, esters,
aldehydes and ketones can form hydrogen
bond with water- make them soluble in water
• Vital in stabilizing 3D structure of DNA, RNA,
and proteins
43
Solvent for Life
• Solution
– Solute
– solvent
• Aqueous solution
• Hydrophilic
– Ionic compounds
dissolve in water
– Polar molecules
(generally) are water
soluble
• Hydrophobic
– Nonpolar compounds
44
Most biochemical reactions involve
solutes dissolved in water.
• There are two important quantitative
proprieties of aqueous solutions.
–1. Concentration
–2. pH
45
Concentration of a Solution
• Molecular weight – sum of the weights of all atoms in
a molecule (daltons)
• Mole – amount of a substance that has a mass in
grams numerically equivalent to its molecular weight
in daltons.
• Avogadro’s number – 6.02 X 1023
– A mole of one substance has the same number of molecules
as a mole of any other substance.
46
Dissociation of Water Molecules
• Occasionally, a hydrogen atom shared by two
water molecules shifts from one molecule to the
other.
– The hydrogen atom leaves its electron behind and is
transferred as a single proton - a hydrogen ion (H+).
– The water molecule that lost a proton is now a
hydroxide ion (OH-).
– The water
molecule with
the extra proton
is a hydronium
Unnumbered Fig. 3.47
ion (H3O+).
47
Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings
• A simpler way to view this process is that a
water molecule dissociates into a hydrogen
ion and a hydroxide ion:
– H2O <=> H+ + OH• This reaction is reversible.
• At equilibrium the concentration of water
molecules greatly exceeds that of H+ and
OH-.
• In pure water only one water molecule in
every 554 million is dissociated.
– At equilibrium, the concentration of H+ or
OH- is 10-7M (25°C) .
48
Water
• Non polar molecule do not dissolve in waterhydrophobic
• Polar molecule dissolve in water – hydrophilic
• Molecule that have both; polar (hydrophilic)
and non polar (hydrophobic) potion –
amphiphatic
• Amphiphatic compound in water will form
structure micelles
49
Micelles
Non Polar Tail- Hydrophobic
Polar Head- Hydrophilic
50
Acid, Bases and pH
• Acid- molecule that act as a proton (hydrogen
ion) donor
• Base – proton acceptor
• Degree of dissociation of acid in water –
 complete dissociation for strong acid
 no dissociation/intermediate – for weak
acid
51
Measuring acid strength
Amount of H+ released when acid is dissolved
in water → acid dissociation constant (Ka)
HA
acid
H+
+A
-
Conjugate base
Ka = [H+][A-]
[HA]
The larger the Ka value, the stronger the acid (completely dissociate)
52
Strong acid
• Strong acid – acid that completely ionize
(dissociate completely) in solution yield one
mole of conjugate acid and base
eg: HCl, H2SO4
HCl + H20
H2SO4 + H20
H30+ + ClH30+ +HS0453
Strong acids and pH
• pH- measure of the concentration of hydrogen
ion in a solution
• The lower the pH, the higher the
concentration of hydrogen ion in solution
pH= -log10 [H+]
54
Example
• Calculate the pH of 0.1M HCl
[HCl] = [H+] = 0.1
Thus, pH HCl= -log [H+]
= -log [0.1]
=1
55
Weak acid
• Acid that only partially dissociate
• It does not release all of its hydrogen's in solution, donating
only a partial amount of hydrogen to solution
• The anion form (base) can accept the proton to reform the
acid
• A weak acid and its base (anion) – conjugate pair
HA
Conjugate acid
A-
+
H+
Conjugate base
56
•The tendency of conjugate acid to release H – K’
•The smaller the
eq value
K’eq, the less tendency to release H – the weaker the acid
K’eq= [H+] [A-]
[HA]
Convenient method in stating K’eq
is in the
form of pK’
pK’=
log
1
K’eq
57
Handerson-Hasselbach Equation (HHE)
• A change in any component in the eq will
further change all component in the equation
A-
HA
Conjugate acid
+
H+
Conjugate base
↑[H+], [A-]↓ , [HA]↑
HHE
Strictly speaking;
pH = pK’ + log [conjugate base]
[conjugate acid]
58
Buffer
• A buffer – something that resist change
• A buffer solution tend to resist change in pH
when small to moderate amounts of strong
acid or strong base is added
• A solution that consist of a weak acid and its
conjugate base
59
Buffer- how it works?
Add 0.1M HCl to
HA
Conjugate acid
A-
+
H+
Conjugate base
60
Electrolytes
• Substance that dissociate in water into cation
and anion – electrolytes
• ions – facilitate conductance of electric
through water (we will see the example later)
• Sugar and alcohols- dissolved in water but do
not carry charge – non electrolytes
61
Medically important weak acid –
carbonic acid (H2C03)
H2C03 – a weak acid formed when C02
dissolved in water
C02+H20
H2C03
(carbonic acid)
H+ + HCO3(bicarbonate)
↑ or ↓ in C02 (air) C02 (dissolved), H2C03, H+ or
HCO3- will cause change in every
component
62
Clinical correlation
Acidosis in cattle
• Acidosis – excessive acid in
body fluids blood pH fall
below 7.35 (normal pH)
1. Due to excessive intake of
carbohydrate
2. Respiratory disease –↑C02
in blood
3. Diarrhea and renal disease –
pH homeostasis altered
63
Clinical correlation
Control of blood pH
• ↑input of bases or buffers (e.g sodium
bicarbonate –NaHCO3)
NaHCO3
Na+ + HCO3HCO3- + H+
H2CO3
H2CO3
C02 + H20
64