Transcript 2 Molecular - bloodhounds Incorporated

Or, Chemistry class in one
lecture!
Key Concepts
 Elements, Atoms, Isotopes etc.
 Chemical formulas, Chemical bonds
 Solutions, Concentrations, pH
 Organic Chemistry / Biochemistry
Element = Building block of
matter
 Periodic Table of the Elements
 In human: 11 major essential
elements C, O, H, Na, Se, P, Mg,
Mn, K, Ca, Fe
= trace elements
 Organic Chemistry = Chemistry of Carbon
Structure of Atoms (AKA elements)
• Some
Terminology:
–
–
–
–
Atomic Number
Atomic mass
Ion
Isotope
Isotopes = Atoms of an element that
have different numbers of neutrons.
Same Atomic Number, variable
Atomic Mass
Most common
Much rarer
Heavy water = ?
Some isotopes are unstable:
Radioisotopes
3 types of radiation:
1.
 radiation – protons and neutrons
1.
Generally not dangerous to life unless inhaled or
ingested
2.
Commonly emitted from radioactive substances like
uranium
3.
Does not travel far
Some isotopes are unstable:
Radioisotopes
1.
 radiation - electrons
1.
Relatively harmless
2.
Medium penetrating power
3.
Can mutate DNA if struck
4.
Used to kill cancer cells
Some isotopes are unstable:
Radioisotopes
1. -Radiation
1.
High energy waves, not particles
2.
Gamma Radiation can penetrate thick material
3.
Since Gamma Radiation is more penetrating it
can cause the most damage to the human body
4.
Gamma knife
1.
Used for benign or malignant tumors of the
brain
Alpha radiation consists of helium-4
nucleus and is readily stopped by a sheet
of paper. Beta radiation, consisting of
electrons, is halted by an aluminium plate.
Gamma radiation is eventually absorbed
as it penetrates a dense material. Lead is
good at absorbing gamma radiation, due to
its density.
http://www.youtube.com/watch
?v=3u_8frR0IpE
• http://www.youtube.com/watch?v=rvAJ_u3
Q0Hw&feature=related
• http://www.youtube.com/watch?v=_W_lLh
Bt8Vg
Nuclear Medicine: use of radioisotopes in
diagnosis & treatment of disease.
is “normal”
iodine
131I has 4 extra
neutrons
127I
 and  radiation
Medical
Imaging ?
Treatment?
The Chemistry of Life
• Elements = Atoms
– Nucleus
• Protons
• Neutrons
– Orbit
• Electrons
Atoms
• Atomic number
• The number of protons,
usually also equals the
number of electrons.
• Atoms must be neutral
• Atoms/molecules that
are stable will not bond
with other
atoms/molecules.
Electron Bonding
• Outermost shell contains all pairs of
electrons
– Stable
• Outermost shell contains at least one
unpaired electron
– Unstable
• Lose, gain or share electrons to become stable
• An atom is most stable when each
electron is paired!
Chemical Bonds
Ionic: electrons pulled from one atom to
another: Na+ and ClCovalent: electrons shared equally
Hydrogen: weak attraction
-Causes surface tension in water.
Chemical Bonds
• Ions
– More (or less) electrons than protons
• Ionic Bonds
– Anions
• Negative
– Cations
• Positive
• Ions are often called electrolytes!
Ionic Bonds
• Give away or receive electrons to create
ions and for each ion to become more
stable
• Ions of opposite charge bind with each
other to form an ionic bond
• An ionic bond typically includes a metal
– NaCl
Ionic Bonding
Important Ions in
Physiology
cations
anions
Chemical Bonds
• Covalent
– Polar
– Non-polar
Covalent Bonds
• Strong bonds that occur when two atoms
share electrons in order to become more
stable
Covalent Bonds
• Non-polar Covalent Bonds
– If the electrons are shared equally between
atoms
• Polar Covalent Bonds
– If electrons spend more time around one atom
than the other
– Molecules develop regions of partial positive
and negative charges
Covalent Bonds
http://www.youtube.com/watch?
v=QqjcCvzWwww
Covalent bond: Water
The electrons are shared equally
If two electrons are shared, that is a
“double bond.”
Chemical Bonds
• Hydrogen Bonds
– Surface tension
– Attractive force
between water
molecules that causes
water to form spherical
droplets
– Weak attractive force
between hydrogen and
oxygen, nitrogen or
fluorine atoms
– Quickly forms and
quickly breaks
Reactions
• Types of Reactions
– Synthesis Reaction--Anabolic
• A+B
C
– Decomposition Reaction--Catabolic
• AB
A+B
– Exchange Reaction
• AB + C
AC + B
• Oxidation-Reduction Reactions (REDOX)
Chemical Reactions
• Reactants form Products
• First Type of Reaction
– Anabolic or Synthesis Reaction
Chemical Reactions
• Decomposition Reaction
– Catabolic
Acid Base Reactions
Acids
– The concentration Hydrogen ions free in
solution
• Protons
– H+
• Bases
– Are proton acceptors
• Bind with hydrogen ions
• Hydroxyl ion = OH• Bicarbonate ion = HCO3-
Buffers
• Buffers resist abrupt and large swings in
the pH of body fluids.
• To resist large changes in pH, the body
releases hydrogen ions when the pH rises
and binds hydrogen ions with bicarbonate
ions when the pH drops.
• Blood pH = 7.35 – 7.45
Buffers
• CO2 + H2O
H2CO3
H++ HCO3-
BIOMOLECULES
• Carbohydrates
• Fats
• Proteins
Organic Compounds
• Carbohydrates
– A group that includes things like table
sugars and starches.
– Includes Simple and Complex groups
Simple Carbohydrates
– Simple
• Monosaccharides
– Fructose
– Glucose
• Disaccharides
– Sucrose
– Lactose
Monosaccharides
Disaccharides
Polysaccharide
Organic Compounds
• Complex Carbohydrates
• Polysaccharides are long branching
chains of simple sugars, specifically
glucose.
– Starch is a storage carbohydrate in plants.
– Glycogen is a storage carbohydrate in animals.
• Liver and muscles
Lipids
• Most diverse group of biomolecules
• Solid at room temp = fat;
– liquid at RT = oil
• Contain much less O2 than CHOs
– Often long chains of C
• 4 categories:
 Fatty Acids can be (un)saturated
 Mono-, di-, and triglycerides
 Phospholipids (polar)
 Steroids
 Eicosanoids (prostaglandins et al.)
 Functions?
Triglycerides
Unsaturated (mono- &
polyunsaturated) fats
are liquid at room temp.
Trans fats have
added hydrogen
(hydrogenated) (p
29)
Triglycerides: 3 FA +
Glycerol
Saturated
Unsaturated
Polyunsaturated
Trans Fats
• In cis bonds, the two pieces of the carbon
chain on either side of the double bond are
either both “up” or both “down,” such that
both are on the same side of the molecule.
• In trans bonds, the two pieces of the
molecule are on opposite sides of the
double bond, that is, one “up” and one
“down” across from each other.
• Naturally-occurring unsaturated vegetable
oils have almost all cis bonds, but using oil
for frying causes some of the cis bonds to
convert to trans bonds.
• If oil is used only once like when you fry an
egg, only a few of the bonds do this so it’s
not too bad.
• However, if oil is constantly reused, like in
fast food French fry machines, more and
more of the cis bonds are changed to
trans until significant numbers of fatty
acids with trans bonds build up.
• The reason this is of concern is that fatty
acids with trans bonds are carcinogenic, or
cancer-causing.
Organic Compounds
• Lipids, Fats or Triglycerides
– Composed of Glycerol backbone plus 3 fatty
acid chains
– Saturated Fats
• Contains only single bonds between the carbons on
the fatty acid chains
• Solid at room temperature
– Unsaturated Fats
• Contains one or more double bonds between the
carbons on the fatty acid chains
• Semi-solid or liquid at room temperature
• Mono, di- and polyunsaturated fats
– Will only dissolve in other lipids and insoluble in
water.
• Like Dissolves in Like
Phospholipid
Phospholipids
Organic Compounds
• Phospholipids
– Modified triglycerides
– Phosphorous head and two fatty acid tails
– Amphipatic
• Hydrophilic, as well as
• Hydrophobic
– Found only in human cell membrane as a bilayer
• Hydrophobic – Tails on the inside of the membrane
• Hydrophilic – Heads on the outside of the membrane
Steroids
Cholesterol decreases
cell membrane
permeability to small
water-soluble
molecules.
Function?
Steroids
Organic Compounds
• Steroids
– Parent compound is cholesterol.
– Used for the production of steroid
hormones.
– Can dissolve in fatty substances.
– Dissolves through cell membrane and
nuclear membrane and attaches directly to
DNA
• Starts Transcription of proteins
– Such as enzymes
– Cholesterol can be produced through denovo synthesis
Organic Compounds
• Proteins
– composes 10 – 30% of cell mass and is the
basic structural material of the body.
– Some are structural.
• Bones, hair, connective tissue
– Some are functional.
• Antibodies, enzymes, protein hormones
Names of the 2
functional groups ?
Proteins
• Made up of amino acids
– Amino = - NH2
• Peptide → oligopeptide → polypeptide → protein
• Most versatile of biomolecules in structure and
function
Learn
these
Amino Acids
Organic Compounds
• Amino acids.
– The Building Blocks of Protein
– Composed of
• an amine groups
• a carboxyl group
• a “R” or Functional group.
– 20 different types of amino acids
• 9 Essential
– Must acquire these through the foods we eat
• 11 Non-essential
– Can be produced through de-novo synthesis
Peptide Bond
Peptide Bonds
• Two united amino acids form a peptide bond or
dipeptide.
• 50 or more amino acids are called a protein or
polypeptide.
• Most proteins contain from 1500 to 50,000 amino
acids in the human body.
Protein Structure
Structural Levels of Proteins
• Primary Structure
– Polypeptide chain
• Secondary Structure
– Alpha Helix
– Beta pleated sheet
• Tertiary Structure
– Alpha helix folds on itself.
• Quaternary Structure
– Hemoglobin molecule
Proteins
• Hydrogen bonds are created within the
Functional Group of the primary
polypeptide chain
• Hydrogen bonds form and break quickly
and can thereby change the protein shape
and its function
Protein Structure
• Globular Proteins
– Compact, spherical proteins
– Have tertiary or quaternary structures
– Also known as functional proteins
•
•
•
•
•
Antibodies
Hormones
Enzymes (catalysts)
Membrane Transporters
DNA Regulatory Proteins for transcription
Proteins
• Fibrous proteins are stable.
• Globular proteins are very unstable.
– Hydrogen bonds can form and break easily.
– Hydrogen bonds can break when:
• pH drops.
• Temperature rises above normal levels.
• Add a PO4 group or other molecules
Adenosine Triphosphate
• The transfer of a high energy phosphate
group to an enzyme causes a change in
confirmation
• The change in enzyme shape allows the
enzyme to quickly catalyze the reaction
Protein Structure
• Change in shape of protein =
– Change in conformation =
– Change in configuration
• Denatured
– When globular proteins lose their shape they
can’t perform their function any longer.
Cellular Metabolism
• Energy as it relates to Biology
– Energy for synthesis and movement
– Energy transformation
• Enzymes and how they speed reactions
• Metabolism and metabolic pathways
– Catabolism (ATP production)
– Anabolism (Synthesis of biologically important
molecules)
Enzymes
• Enzymes are globular proteins that
act as catalysts.
– A catalyst speeds up a chemical
reaction but it itself is not used up
– Enzymes are recycled
• The function of a globular protein depends on the
arrangement of the atoms
• A ligand is any molecule that binds to
another molecule
– A substrate is a ligand that binds to an
enzyme
Mechanism of Enzymes
• Three Basic Steps
– The Enzyme binds with a substrate at its
active site.
– The Enzyme-Substrate Complex is
rearranged to form a product.
– The Enzyme releases the product and
goes back to its original shape
• The Enzyme can be used again to catalyze
another reaction
Enzymes
– The shape of the substrate matches with the
shape of the active site.
– The shape of the active site changes when the
protein is denatured so the substrate can no
longer bind.
Enzymes
• The job of an enzyme is to lower the
activation energy
– Some enzymes carry a helper of “cofactor”
such as iron or copper.
• Vitamins, especially B complex.
Activation Energy
Fig 4-3
Enzyme = Biol. Catalyst
Some important characteristics of an enzyme:
1.
Enzymes are proteins
2.
 rate of chemical reaction by lowering activation
energy
3.
is not changed itself
1.
It may change DURING the reaction
4.
does not change the nature of the reaction nor the
result
5.
is specific
Some more characteristics of
enzymes:
• Usually end in –ase
• Inactive form: -ogen
• in few cases RNA has enzymatic
activity (eg: rRNA  peptide bond)
• Isoenzymes may be produced in different
areas of the body
– E.g., LDH
Naming of Enzymes
mostly suffix -ase
first part gives info on function
examples
• Kinase
• Phosphatase
• Peptidase
• Dehydrogenase
Protein Molecules
• Specificity
– The ability of a protein to bind to a certain
ligand or a group of related ligands
– Some proteins are very specific about the
ligands they bind, others bind to whole groups
of molecules
Affinity
• The degree to which a protein is attracted
to a ligand is referred to as its Affinity.
– High affinity proteins are more likely to bind a
certain molecule than a low affinity protein
Enzyme Activity

Proteolytic Activation (for some)

Cofactors & coenzymes (for some)

Temperature

pH
1.
Other molecules interacting with enzyme
1.
Competitive inhibitors
2.
Allosteric modulators
depends on
Which of the following statements
about proteins is false?
A. All proteins are enzymes
B. A given protein may contain over twenty
different amino acids
C. The tertiary structure of a protein results
from interactions between its amino acids
D. Proteins are gigantic polypeptides
E. All of the above statements are true.
Fatty acids with one or more double
bonds are
A. Unsaturated
B. Have less hydrogen than fatty acids with no
double bonds
C. Generally found in plants
D. All of the above
Cholesterol, while it is not an energy
molecule, has importance in the body
because:
A. It is a stabilizing component of the plasma
membrane and is the parent molecule of
steroid hormones
B. It helps provide essential nutrients to the
brain and lungs
C. It helps mobilize fats during periods of
starvation
D. It enters the glycolytic pathway without being
altered
When ketone bodies are present in the
blood and urine in large amounts, it
indicates increased metabolism of:
A.
B.
C.
D.
Amino acids
Fatty acids
Glycogen
Lactic acid
The atomic mass of an atom
indicates the average total number
of
A. Protons
B. Neutrons
C. Electrons
D. Protons, neutrons and electrons
E. Protons and electrons
Elements that have full outer
shells of electrons
A. Will form many compounds
B. Will normally form anions
C. Will normally form cations
D. Frequently form hydrogen bonds
E. Are inert, and don’t bond readily with
other atoms
Deuterium and Tritium are
examples of
A. Elements
B. Ions
C. Buffering compounds
D. Isotopes
E. None of these
When a molecule is referred to as
polar, it means that
A. The positive and negative charges of the
molecule are unevenly distributed
B. The molecule is ionized and now carries a
charge
C. The molecule is likely to dissolve in water
D. A and C are true
E. All of the Above
When a molecule is referred to as
polar, it means that
A. The positive and negative charges of
the molecule are unevenly distributed
B. The molecule is ionized and now carries
a charge
C. The molecule is likely to dissolve in
water
D. A and C are true
E. All of the Above
The number of protons in the
nucleus of an atom constitutes the
A. Atomic weight
B. Atomic number
C. Atomic mass
D. Nuclear number
A sodium ion, with 11 protons but 10
electrons is
A. Neutral
B. Positively charged
C. Negatively charged
D. Isotope
Suppose you dissolve a little acid in water and
determine that the pH of the solution if 5.2. Now
you add 100 times as much acid to the solution.
Which of the following is the best estimate of the
new pH?
A. 3.2
B. 6.2
C. 7.2
D. 8.2
A polypeptide consists of 100
amino acids. How many
peptide bonds does it contain?
A. 50
B. 100
C. 99
D. 101
E. Impossible to say without
knowing the exact amino acid
composition
Each of the following is a
function of proteins except
one. Identify the exception.
A. Support and structure
B. Transport
C. Carrying of messages
D. Body defense
E. Storage of genetic information
A fatty acid that contains three
double bonds in its carbon
chain is said to be
A. Saturated
B. Monounsaturated
C. Polyunsaturated
D. Hydrogenated
E. Carboxylated
Carbohydrates are stored in the liver
and muscles in the form of:
A.
B.
C.
D.
Glucose
Triglycerides
Glycogen
Cholesterol
The subunits of proteins are called
A.
B.
C.
D.
Fatty acids
Carboxyl groups
Sugars
Amino acids
The bond between an oxygen and
a hydrogen atom in a water
molecule is a(n)
A. Non-polar covalent bond
B. Polar covalent bond
C. Hydrogen bond
D. Ionic bond
4) Molecules interacting with enzyme, cont’d
Allosteric modulators: bind to enzyme away from
active site
change shape of active site
(for better or for worse)
Special case:
= end product inhibition
4) Molecules interacting with enzyme
Competitive inhibitors:
bind to active site
block active site
Fig 4-13
E.g.: Penicillin binds covalently (= irreversibly
to important bacterial enzyme active site)
Active Site:
Small region of the complex
3D structure is active (or
binding) site.
Enzymes bind to substrate
Old: Lock-and-key model / New: Induced-fit model
Reversible Reactions Follow The
Law of Mass Action
Isoenzymes = different models of same
enzyme (differ in 1 or few aa)
Catalyze same reaction but under different
conditions and in different tissues/organs
Examples:
1. Amylase
2. LDH → importance in diagnostics
–
(LDH) Lactate dehydrogenase - Total LDH
will begin to rise 2 to 5 days after an MI; the
elevation can last 10 days.
•
•
140-280 U/L
Normal Adult Range: 0 - 250 U/L
Optimal Adult Reading: 125
1) Proteolytic
Activation
Also
1. Pepsinogen
2. Trypsinogen
Pepsin
Trypsin
2) Cofactors & Coenzymes
Structure:
Inorganic molecules
Cu, Fe, Mg
Function:
conformational change of
active site
Structure:
Organic molecules (vitamin
derivatives, FADH2 ....)
Function:
act as receptors & carriers
for atoms or functional
groups that are removed
from substrate