Midterm Studies Flashcards
What are drugs?
-Pharmaceutical agents that have a biological effect on the human body or some other
living system
-For the purpose of this project, “drugs” include any agent that can elicit a desired
therapeutic effect
Therapeutic agents can be?
- Chemical compounds
- Proteins
- Nucleic Acids
What do drugs target?
1) Proteins
2) Carbohydrates
3) Nucleic Acids
4) Lipids and Membranes
Proteins can be?
- Receptors
- Enzymes
- Transport proteins
- Structural proteins
Carbohydrates can be?
- Cell surface carbohydrates
* Antigens and recognition molecules
Nucleic Acids can be?
- DNA
* RNA
Lipids and Membranes can be?
• Cell membrane lipids
What are the elements of life?
Carbon Hydrogen Nitrogen Oxygen Phosphorus Sulfur
What are the organic compounds?
Alcohol, aldehydes, ketones, carboxylic acid, thiol, primary/secondary/ tertiary amines
what are the functional groups?
hydroxyl, acyl, carbonyl, carboxylate, sulfhydryl, amino, phosphate, and phosphoryl
Fatty acids & lipids are typically comprised of?
Esters and ether
Proteins are typically comprised of?
Amide
Nucleotides are typically comprised of?
Phosphate ester, and phosphoanhydride
Define Macromolecules?
A chain (i.e. polymer) of smaller organic molecules (i.e. monomers)
What are carbohydrates?
- a.k.a. saccharides
- Mostly carbon, oxygen, and hydrogen
- Simple sugar = monosaccharide
- usually contain either 5 or 6 carbons
What are nucleic acids?
-Composed of nucleotides: Adenine (A), Thymine (T), Guanine (G), Cytosine (C), Uracil (U)
-Nucleotides possess: 5-C sugar, a nitrogenous base, at
least one phosphate
-DNA: deoxyribose sugar; RNA: ribose sugar
What is ATP?
Adenosine triphosphate, Central energy carrier in all living cells
What are lipids and membranes?
- Lipids are rich in carbon and hydrogen; possess few oxygen atoms
- Not soluble in water
- Polar, hydrophilic (“water-loving”) head
- Non-polar, hydrophobic (“water-fearing”) tail(s)
- Lipids preferentially form lipid bilayers in aqueous environments: structural basis for all biological membranes
PROPERTIES OF WATER
1) Polarity
2) Hydrogen Bonding
3) The Ultimate Solvent
4) Hydrophobicity
5) Nucleophilicity
BIOLOGICAL FUNCTIONS OF PROTEINS
Biochemical catalysis (i.e. enzymes)
Binding molecules for storage & transport
Membrane pores and channels
Cell structural support and shape
Mechanical work
Regulation during transcription & translation
Hormone and signalling molecules
Receptors
Specialized functions (e.g. antibodies, toxins)
PI STACKING
▪ Interaction between aromatic or heteroaromatic rings
▪ Aromatic rings have regions of high electron density above and below the plane
of the ring.
▪ The atoms in the plane of the ring have low electron density, resulting in a
quadrupole moment
AROMATIC PI STACKING
-quadrupole-quadrupole interactions and Van der Waals forces
▪ Arrangements: sandwich (face to face), T-shaped (edge to face) or parallel displaced
RELATIONSHIP BETWEEN PKA AND PI
pKa can be thought of as the point at which the overall charge of a functional group is zero
Isoelectric point (pI): the pH at which a zwitterionic molecule does not migrate in an electric field because its net charge is zero
POLYPEPTIDES
Linked amino acids in a polypeptide chain are referred to as residues
Amino acids in a chain are identified by either 3-letter code (e.g. Ala, Glu) or 1-letter code (e.g. A, E)
Due to polymerization, most charge from carboxy and amino groups is lost; charges come from side chains
Di-, tri-, oligo- and poly-peptide refers to chains of 2,3, several, or many amino acids
Globular proteins:
water-soluble, compact, roughly spherical; have a
hydrophobic interior and hydrophilic outer surface
Fibrous proteins:
provide mechanical support to cells; typically
assembled into large cables or threads
Transmembrane proteins:
embedded within membranes through stretches of hydrophobic amino acids; act as receptors or signal transducers
Conformation:
a spatial rearrangement of atoms that depends on the rotation of functional groups around single bonds (not dependent on bond breakage)
Configuration:
a spatial rearrangement of atoms that cannot be altered without breaking and re-forming covalent bonds (e.g. stereoisomers)
Transport proteins
▪ Transport polar molecules across the hydrophobic cell membrane
▪ Polar molecules transported include amino acids and neurotransmitters
Enzymes
- Act as catalysts for reactions within the cell
- Present on the inner surface of the cell membrane or within the cell
- Bind the substrates for a reaction and release products
Receptors
- Present in the cell membrane or within the cell
- Act as the cell’s ‘post boxes’
- Receive chemical messages from neurotransmitters and hormones
- Initiate or inhibit chemical signalling processes within the cell
What is X-RAY CRYSTALLOGRAPHY?
- The standard method for protein structure determination
- Involves purifying high concentrations of protein to generate a protein crystal
- X-ray beams are shot through the crystal to get a diffraction pattern, which is
then interpreted to obtain a structure
Challenges of X-RAY CRYSTALLOGRAPHY?
- Getting crystals is difficult
- Membranes do not form crystals
- Protein must be stable at high concentration
- Proteins that have flexible do not crystallize easily
What is CRYO-ELECTRON MICROSCOPY
- Involves the purification of high concentrations of protein, which are flashfrozen to preserve the structure (vitreous ice)
- Proteins are analyzed using a highly powerful electron microscope
- Useful for larger proteins and protein complexes, but only provides information about the surface shape of the protein
What is Nuclear magnetic resonance spectrometry
- Involves the study of proteins in solution; doesn’t need such high
concentrations - Protein is placed in a magnetic field; absorption of electromagnetic radiation of nuclei along with amino acid structure provides information about structure
ATOMIC FORCE MICROSCOPY
Based on the detection of movements of a flexible cantilever containing an atomically sharp probe across a
surface
Uses:
- Determining the molecular weight of a protein
- Protein complexes (including oligomeric state determination)
Advantages of Atomic Force Microscopy
- it is non-destructive
- straightforward sample preparation
- can operate in air or liquid on a wide range of physical properties of the sample
- Can study membrane proteins, including receptor: ligand interactions
define Genome
total genetic content (i.e. inheritable
material) of an organism, organized in one or
multiple chromosomes; can consist of DNA or
RNA
define Gene
a genetic unit which encodes information
necessary for the production of a protein or
RNA
define Catalyst
a substance that speeds up attainment of equilibrium by decreasing the energy required for reaction to proceed
define Substrate
the specific reactant for an enzyme
define Effector
a molecule or protein which elicits an effect on an enzyme (e.g. inhibitor)
define Metalloenzymes
enzymes whose cofactor is a metal
define Prosthetic groups
coenzymes that are bound covalently
six categories of ENZYME CLASSIFICATION
1) Oxidoreductases
2) Transferases
3) Hydrolases
4) Lyases
5) Isomerases
6) Ligases
Derive the Lineweaver-Burk equation from the Michaelis-Menten equation
1) Reciprocal:
2) Redistribute:
3) Lineweaver-Burk:
TYPES OF REVERSIBLE INHIBITION
1) Classical competitive inhibition
2) Non-classical competitive inhibition
3) Uncompetitive inhibition
4) Noncompetitive inhibition
IRREVERSIBLE ENZYME INHIBITION
- Inhibitor forms a stable covalent bond with enzyme, permanently altering it
- Serves to titrate functional enzyme out of the population
- Typically occurs by alkylation or acylation of active site residue side chain
- Can be used to investigate important residues in enzyme active sites
How can ENZYME REGULATION occur
- Total enzyme amount via gene expression and degradation – slow
- Substrate concentration and feedback inhibition - fast
- Allosteric modulation – fast
- Cooperativity - fast
ALLOSTERIC MODULATION
- Allosteric enzymes are those whose activity is altered by change in structure
- Controlled by an allosteric modulator (a.k.a. effector, inhibitor, or activator)
- Modulators are usually small molecules
- Typically reversible and due to non-covalent binding of the allosteric modulator
- Modulators will bind the enzyme at a regulatory (a.k.a. allosteric) site away from the catalytic site
ALLOSTERIC ENZYMES – GENERAL PROPERTIES
- Activities of enzymes are changed by metabolic inhibitors and activators, which do not resemble substrate/product.
- Allosteric effectors bind non-covalently to their cognate enzyme and are not chemically modified.
- Regulated enzymes are usually multi-subunit proteins.
- Enzymes usually has at least one substrate which Vo vs. [S] curve is sigmoidal rather than hyperbolic.
define Pathogen
a biological agent that causes disease or illness to its host
define Infectious Diseases
disorders caused by organisms, such as bacteria, viruses, fungi, or parasites.
define Principle of chemotherapy
A chemical can directly interfere with the
proliferation of microorganisms at concentrations tolerated by the host
define Selective toxicity
chemical shows greater toxicity to microbial cells than
host cells
Define Bacteriostatic
inhibit cell growth; rely on immune system to kill pathogens
Define Bactericidal
mechanism of action actively kills bacterial cells
Define Broad-spectrum
can target a broad range of bacteria (both Gram positive and Gram negative)
Define Narrow-spectrum
will target specific types or species of bacteria (e.g. only tuberculosis)
