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Transcript
BIOCHEMISTRY
What is Biochemistry?
• Biochemistry = chemistry of life.
• Biochemists use physical and chemical
principles to explain biology at the
molecular level.
• Basic principles of biochemistry are
common to all living organism
How does biochemistry impact
you?
• Medicine
• Agriculture
• Industrial applications
• Environmental applications
Principle Areas of Biochemistry
• Structure and function of biological
macromolecules
• Metabolism – anabolic and catabolic
processes.
• Molecular Genetics – How life is replicated.
Regulation of protein synthesis
Principles of Biochemistry
• Cells (basic structural units of living organisms) are highly
organized and constant source of energy is required to maintain
the ordered state.
•
Living processes contain thousands of chemical pathways.
Precise regulation and integration of these pathways are
required to maintain life
• Certain important pathways e.g. Glycolysis is found in almost all
organisms.
• All organisms use the same type of molecules: carbohydrates,
proteins, lipids & nucleic acids.
• Instructions for growth, reproduction and developments for
each organism is encoded in their DNA
5
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
6
Nucleoid region contains the DNA
•Cell membrane & cell wall
• Contain ribosomes (no membrane)
to make proteins in
their cytoplasm
Contain 3 basic cell structures:
• Nucleus
• Cell Membrane
• Cytoplasm with organelles
7
Two Main Types of Eukaryotic Cells
8
Characteristic Bio-membranes and Organelles
Plasma Membrane
A lipid/protein/carbohydrate complex, providing a barrier and
containing transport and signaling systems.
Nucleus
Double membrane surrounding the chromosomes and the nucleolus.
Pores allow specific communication with the cytoplasm. The
nucleolus is a site for synthesis of RNA making up the ribosome
Mitochondrion
Surrounded by a double membrane with a series of folds
called cristae. Functions in energy production through metabolism.
Contains its own DNA, and is believed to have originated as a
captured bacterium.
Chloroplasts (plastids)
Surrounded by a double membrane, containing stacked thylakoid
membranes. Responsible for photosynthesis, the trapping of light
energy for the synthesis of sugars. Contains DNA, and like
mitochondria is believed to have originated as a captured
bacterium.
9
.
Rough endoplasmic reticulum (RER)
A network of interconnected membranes forming channels within the
cell. 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 network of interconnected membranes forming channels within the
cell. A site for synthesis and metabolism of lipids. Also contains
enzymes for detoxifying chemicals including drugs and pesticides.
Golgi apparatus
A series of stacked membranes. Vesicles (small membrane
surrounded bags) carry materials from the RER to the Golgi
apparatus. Vesicles move between the stacks while the proteins are
"processed" to a mature form. Vesicles then carry newly formed
membrane and secreted proteins to their final destinations including
secretion or membrane localization.
Lysosymes
A membrane bound organelle that is responsible for degrading
proteins and membranes in the cell, and also helps degrade materials
ingested by the cell.
10
Vacuoles
Membrane surrounded "bags" that contain water and storage
materials in plants.
Peroxisomes or Microbodies
Produce and degrade hydrogen peroxide, a toxic
compound that can be produced during metabolism.
Cell wall
Plants have a rigid cell wall in addition to their cell membranes
Cytoplasm
enclosed by the plasma membrane, liquid portion called cytosol
and it houses the membranous organelles.
Cytoskeleton
Arrays of protein filaments in the cytosol. Gives the cell its
shape and provides basis for movement.
E.g. microtubules and microfilaments.
http://www.biology.arizona.edu copyright © 1997 - 2004..
11
Biolog. Nanostructures
Biochemistry
12
How did organic complex molecules evolved from
more simple molecules?
CH4, H2O, NH3, HCN
?
Biochemical Evolution
13
How did organic complex molecules evolved from
more simple molecules?
• Urea was synthesized by heating the inorganic
compound ammonium cyanate (1828)
• This showed that compounds found exclusively in living
organisms could be synthesized from common inorganic
substances
14
The Urey-Miller experiment (1950)
Some amino acids could be produced:
15
Many Important Biomolecules
are Polymers
• Biopolymers - macromolecules created by joining many
smaller organic molecules (monomers)
• Condensation reactions join monomers
(H2O is removed in the process)
• Residue - each monomer in a chain
16
17
Molecular Organisation of a cell
18
Water
•About 60-90 percent
of an organism is water
Water is used in
most reactions in
the body
Water is called
the universal
solvent
19
Bio-molecules
• Just like cells are building blocks of tissues likewise molecules are
building blocks of cells.
• Animal and plant cells contain approximately 10, 000 kinds of
molecules (bio-molecules)
• Water constitutes 50-95% of cells content by weight.
• Ions like Na+, K+ and Ca+ may account for another 1%
• Almost all other kinds of bio-molecules are organic (C, H, N, O, P, S)
• Infinite variety of molecules contain C.
•
Most bio-molecules considered to be derived from hydrocarbons.
• The chemical properties of organic bio-molecules are determined by
their functional groups. Most bio-molecules have more than one.
20
Biomolecules – Structure
Anabolic
• Building block
•
•
•
•
Simple sugar
Amino acid
Nucleotide
Fatty acid
• Macromolecule
•
•
•
•
Polysaccharide
Protein (peptide)
RNA or DNA
Lipid
Catabolic
21
Linking Monomers
Cells link monomers by a process
called dehydration synthesis
(removing a molecule of water)
Remove
H
H2O Forms
Remove OH
This process joins two sugar monomers
to make a double sugar
22
Breaking Down Polymers
• Cells break down
macromolecules by
a process called
hydrolysis (adding
a molecule of
water)
Water added to split a double sugar
23
Sugars
• Carbohydrates most abundant organic molecule
found in nature.
• Initially synthesized in plants from a complex series
of reactions involving photosynthesis.
• Basic unit is monosaccharides.
• Monosaccharides can form larger molecules e.g.
glycogen, plant starch or cellulose.
Functions
• Store energy in the form of starch (photosynthesis in
plants) or glycogen (in animals and humans).
• Provide energy through metabolism pathways and cycles.
• Supply carbon for synthesis of other compounds.
• Form structural components in cells and tissues.
• Intercellular communications
24
Monosaccharides -Polysaccharides
Glucose - Cellulose
Glycosidic bonds connecting
glucose residues are in red
25
Fatty acids - Lipids
• Are monocarboxylic acid contains even number C atoms
• Two types: saturated (C-C sb) and unsaturated (C-C db)
• Fatty acids are components of several lipid molecules.
• E,g. of lipids are triacylglycerol, steriods (cholestrol, sex
hormones), fat soluble vitamins.
Functions
• Storage of energy in the form of fat
• Membrane structures
• Insulation (thermal blanket)
• Synthesis of hormones
26
Triglyceride
Glycerol
Fatty Acid Chains
27
Structure of a biological membrane
• A lipid bilayer with associated proteins
28
Steroids
•The carbon skeleton of
steroids is bent to form
4 fused rings
Cholesterol is the
“base steroid” from
which your body
produces other
steroids
Cholesterol
Estrogen
Testosterone
Estrogen &
testosterone are also
steroids
Synthetic Anabolic Steroids are variants of testosterone
29
Nucleic Acids
•Store hereditary information
Contain information for making all the
body’s proteins
Two types exist --- DNA & RNA
30
Amino acids - Proteins:
• Amino acids:
•
Building blocks of proteins.
•
R Group (side chains) determines the
chemical properties of each amino acids.
•
Also determines how the protein folds and
its biological function.
•
Functions as transport proteins, structural
proteins, enzymes, antibodies, cell
receptors.
31
Proteins as Enzymes
• Many proteins act as biological catalysts or enzymes
Thousands of different enzymes exist in the body
Enzymes control the rate of chemical reactions by
weakening bonds, thus lowering the amount of
activation energy needed for the reaction ->
Catalysator
-> No not interfere with the equilibrium of reaction
-> Enzymes are reusable !!!!
32
Enzymes:
• Active site - a cleft or groove in an enzyme that binds the
substrates of a reaction
The nature and arrangement of amino acids in the
active site make it specific for only one type of
substrate. (accepts just one enaniomer)
Egg white lysozyme
33
Macromolecules
34
Macromolecules
35
Concepts of Life
Life is characterized by
•
Biological diversity: lichen, microbes,
jellyfish, sequoias, hummingbirds, manta
rays, gila monsters, & you
• Chemical unity: living systems (on earth)
obey the rules of physical and organic
chemistry – there are no new principles
36
Life needs 3 things:
(1) ENERGY, which it must know
how to:
•
Extract
• Transform
• Utilize
37
The Energetics of Life
• Photosynthetic
organisms capture
sunlight energy and use
it to synthesize organic
compounds
• Organic compounds
provide energy for all
organisms
38
Using toxic O2 to generate energy
2 H2O  O2 + 4e- + 4H+ (photosynthesis)
Glucose + 6O2  6CO2 + 6H2O + Energy
39
Glycolysis: the preferred way for the
formation of ATP
40
Life needs (2) SIMPLE MOLECULES,
which it must know how to:
• Convert
• Polymerize
• Degrade
41
Life needs (3) CHEMICAL
MECHANISMS, to:
• Harness energy
•
•
•
•
•
•
Drive sequential chemical reactions
Synthesize & degrade macromolecules
Maintain a dynamic steady state
Self-assemble complex structures
Replicate accurately & efficiently
Maintain biochemical “order” vs outside
42
Trick #1: Life uses chemical coupling to
drive otherwise unfavorable reactions
43
Trick #2: Life uses enzymes to speed up
otherwise slow reactions
44
How does an enzyme do it,
thermodynamically?
45
How does an enzyme do it,
mechanistically?
46
Chemical reaction types encountered in
biochemical processes
1. Nucleophilic Substitution
• One atom of group substituted for another
2. Elimination Reactions
• Double bond is formed when atoms in a molecule is removed
3.
•
•
•
Addition Reactions:
Two molecules combine to form a single product.
A. Hydration Reactions
Water added to alkene > alcohol (common addition pathway)
47
4. Isomerization Reactions.
• Involve intramolecular shift of atoms or groups
5. Oxidation-Reduction (redox) Reactions
• Occur when there is a transfer of e- from a donor to
an electron acceptor
6. Hydrolysis reactions
• Cleavage of double bond by water.
48
Biochemical Reactions
•
Metabolism: total sum of the chemical reaction happening in a
living organism (highly coordinated and purposeful activity)
a.
b.
Anabolism- energy requiring biosynthetic pathways
Catabolism- degradation of fuel molecules and the production of
energy for cellular function
•
All reactions are catalyzed by enzymes
•
The primary functions of metabolism are:
a. acquisition & utilization of energy
b. Synthesis of molecules needed for cell structure and
functioning (i.e. proteins, nucleic acids, lipids, & CHO
c. Removal of waste products
49
Even though thousands of pathways sound very
large and complex in a tiny cell:
• The types of pathways are small
• Mechanisms of biochemical pathways are simple
• Reactions of central importance (for energy
production & synthesis and degradation of major cell
components) are relatively few in number
50
Energy for Cells
• Living cells are inherently unstable.
• Constant flow of energy prevents them from
becoming disorganized.
• Cells obtains energy mainly by the oxidation of biomolecules (e- transferred from 1 molecule to another
and in doing so they lose energy)
• This energy captured by cells & used to maintain
highly organized cellular structure and functions
51
52
ENVIRONMENTAL BIOCHEMISTRY
METABOLIC RESPONCES TO THE ENVIRONMENTAL FACTORS AND THE LIMITS OF
CHANGES THERE OF,LEADING TO ADAPTATION.
EFFECTS OF VARIATION IN ATMOSPHERIC TEMPERATURE & CHEMICAL STRESS IN
FORM OF AIR, WATER AND FOOD POLLUTION.
ALTERATION IN ATMOSPHERIC TEMPERATURE
EXPOSURE TO COLD STRESS
TYPES OF INJURY: LOCAL(FROSTBITE) & GENERAL(HYPOTHERMIA)
COMPENSATORY MECHANISM
1. SHIVERING PHASE (INVOLVEMENT OF SKELETAL MUSCLE)
2. NON SHIVERING PHASE (NON SHIVERING THERMOGENESIS OR CHEMICAL
THERMOGENESIS)
~NUTRITIONAL MODIFICATION
INCREASED COMBUSTION,RISE IN TYROSINE TRANSAMINASE &
TRYPTOPHANPYRROLASE ALSO INCREASE IN ARGINASE.
~LIPID METABOLISM
DECREASE IN TOTAL FFA,ROLE OF BROWN ADIPOSE TISSUE
~CALORIGENIC SHUNT
INCREASED GLYCOLYSIS,GLUCONEOGENESIS,ROLE OF ETC.
~HORMONAL EFFECT
ROLE OF THYROID HOMONE
EXPOSURE TO HEAT
HEAT BALANCE & HEAT STRESS (MUST BE DISSIPATED)
VARIOUS FACTOR EFFECTING IT.
EFFECTS OF HEAT STRESS
~HEAT STROKE
~HEAT HYPERPYREXIA
~HEAT EXHAUSTION
~HEAT SYNCOPE
CHEMICAL STRESS AND POLLUTION
AIR POLLUTION
1.POLLUTANTS & CONTAMINANTS
2.SOURCE
INDUSTRIAL
COMBUSTION
MOTOR VEHICLE
MISCELLANEOUS
3.INDICATORS
SULPHURDIOXIDE
SMOKE INDEX
SUSPENDED PARTICLES
HEALTH EFFECTS OF AIR POLLUTION
1. OXIDES OF SULPHUR
INJURY TO RESPIRATORY SYSTEM
DAMAGE TO LUNG TISSUE
2. OXIDES OF CARBON
CO2 ADAPTATION:CHANGE IN ACID BASE EQUILIBRIUM
CO TOXICITY: HYPOXIA,REACTION WITH Hb.
3. PHOTOCHEMICAL OXIDANTS
SECONDARY PRODUCTS OF NITROGEN OXIDE
EYE AND LUNG IRRITATION , ASTHMA
4. PARTICULATES
PULMONARY ABNORMALITIES
SIDEROSIS(IRON)
ASBESTOSIS(ASBESTOS)
ANTHRACOSIS(SOOT)
BYSSINOSIS(COTTON DUST)
SILICOSIS(SILICA)
BAGASSOSIS(SUGARCANE,RICE)
OTHER EFFECTS OF AIR POLLUTION
WATER POLLUTION
1.ORGANIC POLLUTANTS
a. SEWAGE,WASTE FROM TANNRIES,PAPER MILLS, FOOD
PROSSESING INDUSTRIES.
DECREASE DISSOLVED OXYGEN
PATHOGENIC MICROORGANISM , EUTROFICATION
b. SYNTHETIC ORGANIC CHEMICALS
( PLASTIC,PAINTS,PHARMA WASTE)
c. PESTICIDES
CLASSIFICATION
~CHLORINATED HYDROCARBON
(DDT,ALDRIN,DIELDRIN) ENTERS FOOD CHAIN
~CHLOROPHENOXY ACID
(ATRAZINE 2,4-D)
~ORGANOPHOSPHORUS
( MALATHIONE,DIAZINONE) NEUROTOXIC,INHIBITOR
OF CHOLINESTERASE .
2.INORGANIC POLLUTANTS
HEAVY METAL POLLUTANTS
~ENTER INTO FOOD CHAIN
~AFFINITY FOR SULPHUR;ATTACK SULPHUR BONDS IN ENZYMES
~OTHER VULNARABLE SITES ARE COOH OF PROTEIN ALSO BIND TO CELL
MEMBRANE.
A. ORGANIC MERCURIAL: INCECTISIDES & BACTERICIDES, NEUROLOGICAL
DISORDERS
B. CADMIUM: UNCOUPLER OF OXIDATIVE PHOSPHORYLATION
C. BERYLLIUM :PHOSPHATE INHIBITOR
D.STRONTIUM :COMPETITOR FOR CALCIUM IN BONE
E. LEAD
~GUIDELINES ON PREVENTING LEAD POISONING BY US CDC.
~ANY CHILDREN UNDER 6 YEARS OF AGE WITH BLOOD LEAD
LEVEL <10 μg/dl
~IN ADULTS ITS < 60 μg/dl
~SOURCE -- UBIQUITOUS IN ENVIRONMENT (PAINTS & TETRAETHYL
LEAD)
~CLINICAL FEATURES
IN CHILDREN IS MENTAL RETARDATION,SLOW LEARNING,
BEHAVIOURAL CHANGES, LOSS OF 4-5 IQ POINTS FOR EACH
10 μg/dl OF BLOOD LEAD
IN ADULTS MENIFESTATIONS ARE NEUROPATHY
ENCEPHALOPATHY , ABDOMINAL PAIN & SEVERE ANEMIA.
~LEAD INHIBIT
ALA-SYNTHASE, ALA DEHYDRATASE, FERRO CHELATASE
F. ARSENIC
SOURCE : FRUIT SPRAYS , RAT POISON , PESTICIDES ETC.
TOXIC EFFECTS: DIZZINESS CHILLS CRAMPS & PARALYSIS
INHIBIT SH ENZYME INTERFERES WITH CELLULAR METABOLISM
ALSO CAUSES INTRAVASCULAR HEMOLYSIS.
OTHER CHEMICALS
~FLOURINE
~UV RADIATION
~CFC’s AND HALONS
~RADIOACTIVE MATERIAL
FOOD POLLUTION
I. PROCESSING OF FOOD
•
PRE PACKAGING -- CONTAMINATION BY salmonella & staphylococcus aureus.
•
PACKING – BOTULISM
•
FOOD ADDITIVES – ANILINE , CYLAMATE , MONOSODIUM GLUTAMATE
II. NATURAL TOXIN
•
LATHYRISM—NEUROTOXIN PRODUCE BY Lathyrus sativum
•
FAVISM—IN G6PD DEFICIENT INDIVIDUALS
•
ALKALOIDS—MUSCARINE IN MUSHROOMS
•
GOITROGENS—THIOOXAZOLIDON DERIVATIVES (CABBAGE,TURNIP)
THIOCYANATES & ISOTHIOCYANATES (RAPESEEDS,MUSTARD)
III.STORAGE CONTAMINATION
FUNGAL GROWTH IN MOIST CONDITION
~AFLATOXIN,ERGOTOXIN
IV.ADULTRATION OF FOOD
~EPIDEMIC DROPSY
~ENDEMIC ASCITES
SUMMARY OF THE CHAPTER
ENVIRONMENTAL BIOCHEMISTRY
ALTERATION IN
ATMOSPHERIC
TEMPERATURE
~COLD STRESS
~HEAT STRESS
CHEMICAL STRESS & POLLUTION
AIR
~SOURCES
~INDICATORS
~HEALTH EFFECT
~OTHER EFFECT
ACID RAIN
GREENHOUSE EFFECT
GLOBAL WARMING
WATER
FOOD
FACTORS
~PROCESSING
~NATURAL TOXINS
~DURING STORAGE
~ADULTERATION
~SOURCE
~ORGANIC
~INORGANIC
HEAVY METAL(LEAD,ARSENIC)
~OTHERS