BMS 1004

EXAM #1 review
negalizu
Basic Chemistry
• Molecules are made of atoms
• Atoms = nucleus + electrons around
in orbit
• Atom mass = protons + neutrons
• Atom identity = # protons in nucleus
 Bulk

• C-H-O-N-P-S-Na-Cl-K,Ca

Elements Trace

• Mg – Mn – V – Cu – Cr –
Co – Fe – Ni – Zn – Mo –
Se - I
 Elements – Valence E

1 2 3 4 5 6 7 8
H He B C N O F Kr
Na Mg P S Cl
K Ca I
Elements – Charges

1+ 2+ 3 4 -1 -2
+ +
H Mg B C Cl O
Na Ca I S
K OH
 Elements – Bonds

1 2 3 4 3 or 5 2 or 6
H O N C P S
Cl
Hydrogen Bonds
• Hydrogen bonds are an additional type of bond that exists
mostly between oxygen or nitrogen to only those
hydrogens that are covalently attached to oxygen or
nitrogen.
• H attached to O can H-bond to non-bonding electrons of O or N
• H attached to N can H-bond to non-bonding electrons of n or O
Water
molecule
• Polar – because O is more
electronegative than H
• Bent – because 2 bonds H
plus unpair electrons of O
form a tetrahedron shape
 As more polar groups such OH, Amines, Carboxylic
Acid, etc. more soluble. Just identify the functional
groups in the molecule to determine if molecule is
hydro-soluble, liposoluble, or amphiphilic

Organic When dissolve NaCL in water the negative part of

molecule water (-O) attaches to the positive part of salt (Na+),
and the positive part of water (H+) attaches to the
solubility negative part of salt (Cl-). (forming hydration shell).

in water When two Water molecules interact form Hydronium

(H3O). One H2O accept one proton.
Functional
Groups
Functional Groups
Considerations
• Lipophilic functional groups
• Alkanes , Alkenes, Aromatic hydrocarbons, Alkyl or Aromatic halides
• Hydrophilic functional groups
• Ionized, Amines, Carboxylic Acids, Hydroxyls
• Interactions
• Intermolecular – ion ion, ion-dipole, dipole-dipole, H-Bonds, Van Der Waals
• Adverse Events
• Drug Interactions
• Pharmacokinetic - (ADME)
Functional Groups

Auxophore – non-
Pharmacophore – essential (removing this
essential group will no affect any
important thing)
 • Phosphates are charged in biological systems
•  Physicochemical properties - refers to how the
functional groups present within a molecule

Cont.
influence its acid–base properties, water solubility,
partition coefficient, crystal structure,
stereochemistry, and ability to interact with
functional biologic systems
• electric effect (resonance, polar, non-polar)

groups • Steric effect – shape

• Solubility – Hydrophilic (aqueous media) or Lipophilic
(organic media)
• Hight logP = lipophilic
• Low LogP = Hydrophilic
Cont. functional groups
• Optical Activity
• Chiral
• Enantoimers – often have different activity
• Enantiopure- more active/potent enantiomer
Organics Reactions in Biological Systems

In Vivo
• Nucleophilic addition
• Redox

How drugs react in the body

• intermolecular reactions (commonly)
• Forming and Breaking bonds
• Drugs react mostly in GI system
• Amides and Esters could be hydrolyzed in vivo
Drug reactions
Acid Drugs Basic Drugs
Ionized (charged) in basic environment (intestine) Ionized (charged) in acid environment (stomach)

No ionize (neutral) in acidic environment (stomach) No ionize in basic environment

No ionize drugs – are liposoluble and pass-through biological membrane

Ionized drugs – are Hydro soluble and can't pass through biological membrane

In summary there are three things to figure it out

1. it’s the drug mostly acidic or basic
2. What’s the pKa (pH at which # ionized = # non ionized molecules)
3. pH into which the drug is going to be placed
pH and pKa
pH and pKa
• Neutral pH
• pH = pOH = 7
• For all other pH’s
• pH+pOH = 14
• pH>pka = acid
• pH<pka = basic
Cont…pH and
pKa

• For weak acids and bases
[A ]
pH  pK a  log
• pH=pKa

• Henderson –Hasselbach equation [ HA]

explain the relation between pH and
pKa
Cont... pH and pKa
• Titration curve
• Involves the gradual addition (makes solution more acid) or removal (makes
solution more basic) of protons (H+) by addition of a base
• Can be used to determine the equivalence point of an acid/base reaction
• Tell us when we can reach equilibrium point
• Must buffer work better within 1pH unit of its pKa
• The middle point of the titration curve = pKa
• Buffers are made using weak acid and its conjugated base
Life Basics
Live
organization
• Body-Organs-cells-organelles
 Nucleus – (replication takes place) – contains genetic
information (DNA, mRNA & tRNA).

Nucleolus – (transcription takes place) – contains DNA

for RNA Synthesis

Nuclear envelopment – double membrane continuous

Organelles to rER

rER – contain ribosomes. Is a system of channels that

transport proteins (its where protein chain grows)

Ribosomes – (translation takes place)- protein

synthesis in the cytoplasm
 sER – protein modification and membrane synthesis

Golgi complex – protein sorting

Peroxisomes – digestion using H2O2

Cont. Lysosomes – digestion using enzymes (needs low pH)

Organelles
Endosomes – contains extra cellular material and memebranes
Mitochondria – energy – ATP

Vesicles – transport

Cytoskeleton – structure
Cytoskeleton
• Function
• Cell structure
• Motility
• Adhesion
• Structure
• Microfilaments – two strands of actin. Related to movement when attached to
myosin
• Intermediate filaments – keratin - related to cell junctions
• Microtubules (MOTOR)
• Form cilia, flagella and centrioles
• Proteins
• Kynesin (+) (neuron axons)
• Dynein (-) (neuron axons)
• Myosin (muscle)
Cellular Junctions
Summary
Cellular
Junctions
• Tissues, Organs and
Systems are the result
of associations of
different types of cells
 • Tight junction
• Two epithelial cells attached together very
tight using proteins
Cellular • Claudins
• Ocludins
Junctions • Attached to the terminal web of actin
• Adherens junctions (Zonula Adherens)
between • Starts the process of join two epithelial cells
• Allows for stretch
epithelial • Connect microfilaments
• Main protein – Cadherins – need Ca+
cells
 • Desmosomes/Hemidesmosomes
• Stretch junctions (a lot in the skin)
Cont… • Cadherins attached to intermediate filaments
• Between contiguous cells of basal area
Cellular • Gap junctions

Junctions • “tunnels” or “bridges”connecting two cells that

allows transport of small molecules between
each other
between • Protein

epithelial cells • conexins

Cellular adhesion proteins
• Integrins
• attached to intermediate filaments
• Attach cells to its underlying membrane in the basal lamina
• Cadherins – Ca+ dependents
• IgG – overlapping iG domains, link cells
• CAM’s – no CA+ dependent
• Selectins – found in vascular system (P, L. E)
Osmolarity
 • Osmotic pressure – Pression must be applied to a
solution to avoid inward flow of H2O
• Diffusion - movement of molecules along

Osmotic concentration gradient

• Osmosis – movement of small molecules across

Pressure
semi-permeable membrane
• Oncotic pressure – Osmotic pressure exerted by
plasma protein
• Osmolality - # moles of osmotically active
molecules per Kg solvent
Cont…Osmotic Pressure
Osmolarity – Moles solute/L solvent
# of moles osmotically active per Liter of solvent
Independent of type of solute and ions
Electrolytes and non-electrolytes contribute to osmolarity.
Tonicity –ability of solution to cause cell shrink or
swell
Isotonic solution – no net water movement
Hypotonic solution – cause cell swell
• To low solute inside cell, so, to much water will move into the cell
Hypertonic solution – cause cell shrink
• To much solute inside cell, so, water will move outside the cell
 • Osmolarity of Non-Electrolyte = 1xM (M=Molar
concentration)
Cont…Osmotic • Osmolarity of Electrolyte = n x M (n= # of ions in
the electrolyte)
Pressure • NaCL (2 ions) if concentration is 1M then 1 x 2
= 2 Osmols
Homeostasis
Balance of internal environment
Components
• Sensor – stimulus – produce change to a variable
• Afferent pathway – (in-put) change detected
• Integration Center (CNS)
• Efferent Pathway (output)
• Effector (response)
Control mechanism
• Positive feedback
• Potentiate initiate stimulus
• Example – During childbirth Oxytocin Hormone intensifies and speeds up contraction
• Negative feedback
• Primary mechanism to keep homeostasis
• Reduce the original effect of the stimulus
• Example – Glucose control. When blood sugar levels raises, pancreas secret insulin to
low sugar level.
Biological membrane
summary
Membrane
Structure
• Lipids
• Phospholipid bilayer
• Cholesterol – fluidity
• Carbohydrates
• Proteins
Structure
• Lipids
• Phospholipids
• Principals responsible of the membrane function
• Two fatty acid chains attached to two C atoms in a
glycerol molecule
• Fatty acid chain – hydrophobic
• 3rd C of glycerol is attached to a phosphate group negative
charged makes it hydrophilic
Phospholipid
bilayer
• The amphipathic characteristic
and its cylindric shape are
responsible of the bilayer
formation
 • Proteins
Cont. Structure • Different sizes and shapes
• Associated or embedded to the bilayer in a mosaic pattern
Membrane proteins
• Function
• Anchor – (integrins)
• Transport – ion channels and gated ion channels
• Enzymatic (breakdown chemicals to terminate its effect)
• Receptors – (hormones)
• Markers – distinguish between body cells and foreign cells
• adhesion – occludins, adherins, desmosomes
Membrane permeability
• Permeable for some substances - if allows its passage trough
• Impermeable – It does not allow the pass of certain substances
• Fluid mosaic structure gave it a selective permeability characteristic
(semipermeable)
• Biological membranes are more permeable to non-polar substances
Membrane
transport
Simple diffusion

NO CARRIER NEEDED NET FLUX DETERMINED BY MOVEMENT OF MOLECULES

GRADIENT BASED ON THERMAL MOTION
Simple diffusion – factors affect the Flux

Inversely Directly
• Molecule weight • Concentration gradient
• Membrane thickness • Surface area
• Membrane permeability
• Temperature
cont… Simple diffusion
• Fick’s Law of diffusion (Flux) = rate at which diffuse over time

J=−DA ∆C/∆x
• ΔC = concentration gradient
• Diffusion coefficient (molecular weight, temperature)
• Δx = Membrane thickness
Membrane transport
• Passive diffusion: NO energy – Flow down gradient
1. Ion Channels (very fast flux)
• Very specific
• Gated (closed most of the time)
• Things can open it – Ligand bind, change in membrane potential, post translation modification
(Phosphorylation), pressure (put pressure on the skin)
• Movement of ions generates charge
2. Carrier mediated
• Specific
• From [high] to [low]
• Require binding molecule to carrier and to conformational change
> ion chanel > mediated carrier > simple
diffusion

Flux
Osmosis
• Passive diffusion of water
• No ATP require
• Move down the concentration
gradient
• Movement based on # of particle
present
• H2O will move From area of less solute
to area with more solute
Tonicity – • Isotonic - both environment has = solute concentration
• Water will no move

ability of a • Hypertonic – solute concentration is higher than the environment with which it is
compared

solution to • Hypotonic – solute concentration lower than environment with which it is

compared

cause cell to • WATER WILL ALWAYS MOVE FROM AREA WITH LOWER SOLUTE TO A HIGHER

shrink or SOLUTE
• the environment into which the water moves can swell

swell • the environment from which the water comes out can shrink
Tonicity and Osmolarity
• Glucose, Urea, Mannitol – permeable
• Ions – impermeable
• Take into consideration:
• Permeable solute not contribute to the tonicity
• In an exercise with permeable solute, you can ignore it because is like
placing the cell in pure water (very hypotonic).
Tonicity and Osmolarity

1. When put a cel 300mOsm in 1 L solution of 300 mOsm/L NaCl and 300 mOsm/L
Glucose.
Answer: 1. Don’t need to calculate osmolarity because is in the excersice (if was
Molarity instead, then you must calculate osmolarity). 2. then solution are
isoosmolar. 3. Cell Tonicity - isotonic.

2. When put a cell 300mOsm/L in 1 L solution of 150 mOsm/L NaCl and 150
mOsm/L Glucose
Answer: 1. Ignore Glucose. 2. Don’t calculate. 3. Solution is hypoosmolar in respect
to the cell 4. Cell tonicity will be hypotonic because Water will move from less
solute area (outside cell) to a higher solute area (inside cell) causing the cell to swell.
Fats and lipids
Main difference between fats and lipids
Fats
• Are form of lipids
• Oily material – under the skin and
surrounding organs (adipose tissue)
• Two kinds – saturated (single bonds)
and unsaturated (double bonds, cis or
trans)
• Solid
• Source of energy (fatty acids ester of
glycerol)
Lipds
• Large macromolecules in the body
• Organic molecules soluble in organic
solvents, insoluble in water
• Three main categories –
triglycerides, phospholipids and
steroids
• Solid or liquids
• Structural function and source of
energy
Adipose tissue (body fat)
• WAT – white adipose tissue • BAT – brown adipose tissue
• Subcutaneous region (upper and • Predominant in infant
lower body • Provides energy (babies)
• Barrier against dermal infection
• Insulator prevent heat loss
• Cushion protection
• Visceral region
• Around vital organs
Main lipid's role
• Component of the cell membrane's structure
• Production of hormones (most steroids such estrogen, testosterone, progesterone)
• Steroid hormones are lipids derived from cholesterol
• Meal digestion and absorption
• Signalling
Cont…Fatty acid's structure
• Carboxyl group (polar*) + Long Chains of C-H (non-polar**)
• As longer the C-H chain the higher the melting point but lower the water
solubility
• Saturated - Single bonds
• Solid at room temperature
• High melting points

*Polar-water soluble
**Non-polar – water insoluble
Cont…Fatty
acid's structure
• Unsaturated - Double bonds
• Monounsaturated – one double bond
• Polyunsaturated – multiple double bonds
• Liquid at room temp.
• Solid when chilled
• Cis – H are on the same side (in respect to a double bond)
• Bent shape
• Thermodynamically less stable – low melting point
• oils
• Trans –H are on opposite side (in respect to a double bond)
• Straight chain
• Solid at room temperature
• thermodynamically more stable - High melting points
• solids
Cont…Fatty acid's structure
• Polyunsaturated fatty acids
• Last C of the tail is called Omega
• Classified by their Omega #
• Omega3 (double bond between C 3-4)
• Omega6 (double bond between C 6-7)
• Omega9 (double bond between C 9-10)
Triglyceride
s
• Three fatty acids join to a
glycerol molecule by ester
bonds. Stored in
adipocytes. Insoluble in
water.
 • Are neutral because the fatty acid polar side are
bonding to a glycerol molecule by a covalent bond.
(ester bond=esterification=condensation reaction)
• The result of condensation is a triglycerol molecule +
3 H2O
• Ester bonds are important because they can’t be
Cont… broken down by enzymes in the body.
• To break down ester bonds there’s a needs of
Trigycerides Hydrolysis
• Lipases are water soluble enzymes that catalyzes
ester bonds hydrolysis in triglycrides

condensation (esterification)

Glycerol + 3 fatty acids = triglycerides + H2O

hydrolisis
Glycerophospholipids
• 2 fatty acids attached to the 1rst and 2nd C of glycerol by ester bonds
• Polar or charged group is attached to the 3rd chain via phosphodiester bond
• Glycerol is pro-chiral
• When phosphate is attached at one end, glycerol is converted to a Chiral compound
• Phospholipases degrade glycerophospholipids and catalyze hydrolysis at specific
positions within the structure
• Chirality importance
• Orientation and interaction with receptors or other drug molecules
• Chemical properties such MP
• Physical properties (Packing and orientation)
Glycerophospholipids
• All glycerophospholipids has
• Phosphate group negative charged
• The polar alcohol group may be negatively charged, positively charged or neutral.
 • Steroid lipid
• Major sterol in animals
• Precursor of steroid hormones (estrogens,
androgens, etc)
Cholesterol • Essential component of plasma membrane
• Fluidity
Sphingolipids
• Sphingosine instead of glycerol
• Three classes (All derivative of ceramides)
• Sphingomyelins
• Mainly found in nervous tissue membrane (Myelin and insulated axons)
• No charged
• Have a choline head group
• Glycosphingolipids
• Mainly found in the outer leaflet (outer layer of membrane)
• No phosphate group
• Head group with sugar
• Cerobrosides
• Sugar link to a ceramide
• In membrane of nonneural tissue
• Important as antigens and cell receptor
 Sphingosine + fatty acid
= ceramide
Cont.Sphingolipid Are abundant in nervous
s
summary tissue plasma membrane
Define human blood
groups (A,B,O)
Nucleotides
Nucleic acids
Nucleotides
MONOMERS
 Sugar
 N. Base (complementary bonded by H-BONDS)
 Phosphate group
•What keeps DNA strand together are the H-Bonds, Van Der Waals
forces and hydrophobic effect.
•Nucleotides has two synthetize Pathway and both uses PRPP
synthetase
• 1. De Novo Pathway
• 2. Salvage Pathway.
Nucleic Acids
linear POLYMER of nucleotides bonded by phosphodiester bonds
 DNA
o Form a double helix (two antiparallel strands)
o Function – store genetic information in sequences of N.Base that will be used
to build proteins.
 RNA
o Single strand
o Function – transcribe DNA information in a language that cell could read to
form proteins in the ribosomes
Gene expression
Regulation of gene
expression
1. It’s a multiple step process by
which genetic code is used to
make functional protein
2. Functional protein are essential for
the proper function of human
body
3. If the process of making functional
protein is disturbed, this leads to a
state of disease
Regulation of gene
expression steps
Transcription

Post transcriptional modification

Translation

Post translational modification

Functional protein
Transcription
• RNA polymerase makes RNA using DNA template
• Various proteins and enzymes work together to determine which part of DNA transcribe, when and how much
• Proteins that control what type of protein made = transcription factors
• Transcription factor can identify special sequences in a DNA called promotors
Transcription factors control the entire process – are very specific depending on the protein that going to be
synthetize
• Activators – regulatory proteins that bind to the promote regions (enhancer) and assits the binding RNA
polymerase to the adjacent promoter
• Are specific factors depending on the protein synthetizing
• increase transcription
• Repressors – decrease transcription
Cont… transcription
• In general, the process is
1. Activator bind to the enhancer region of the promotor
2. Step 1 causes DNA molecule bent
3. Transcription factors bind to the promoter site
4. RNA Polymerase start the transcription
5. Transcription ends in the termination site
Cont… transcription
IMPORTANT DETAILS
• Before all this steps, DNA are in form of chromatin wound around histones
proteins. The chromatin must be activated by acetylation (add an acetyl
group). When Methyl is added instead of acetyl chromatin is deactivated.
(slide 8 gene expression)
• transcription factors must be activated, how with a protein kinase. If we want
to deactivate them, a protein phosphatase is used.
• Housekeeping genes are genes that constitutively express no matter what
• Histones
• ATPase
Post transcriptional modification
• Once the transcription ends, the mRNA chain is created but it has
parts that code for the protein we want (exons) and parts that do not
code (introns)
• RNA made during transcription (hnRNA) must be modified and
processed in order to convert it to mRNA
• This modifications are Splicing (removal of introns), addition of PolyA
tail, and addition of 5 prime cap
• mRNA produced is transported to ribosome
Translation
1. mRNA enters a ribosome and with the use of amino acids, tRNA’s
and GTP, a protein is made
2. Protein trafficking - meaning that protein will be send to its
destination
1. Protein destined to stay inside cell ar made in cytosolic ribosomes
2. Protein destines to be excreted , reside in the plasma membrane or an
organelle are made in endoplasmic reticulum ribosome

Certain antibiotics work by inhibiting this step in bacterial cells

Post Translation Modification
• Proteins made during translation must be modified in order to be
functional
• Proteins can undergo several types of post translational modification
• Covalent alteration
• Cleavage
• Folding (using chaperon)
Summary
• Successful gene expression requires the ability to create proteins (transcription,
translation), regulate protein creation (gene regulation) and send protein to the correct
location (protein trafficking)

• Disturbance in any those process can lead to a disease