New Medical Education Curriculum- Semester 2 (2023)
Biomolecules
Dr Sheelan Ata Talabani
B.Sc. Biology (University of Baghdad)
M.Res. Biomolecular Sciences (University of York, UK)
Ph.D. Protein Structure & Function (University of York, UK)
Intended learning outcomes:
•
•
•
•
•
•
•
•
•
Chemical bonds in macromolecules.
Hydrophobic and hydrophilic molecules.
pH, pKa and buffers.
Amino acids structure & peptide bond.
Amino acid classification.
pH affect on amino acids’ charges.
Isoelectric point of a protein.
Amino acids & Proteins functions.
Other biomolecules: Nucleic acid, Lipids & carbohydrates.
The molecules of life
Water
Ions
Small energy molecules like ATP, GTP, NADH.
Small molecules: Sugars, vitamins, fatty acids, amino
acids and nucleotides.
Macromolecules: DNA, RNA, Proteins, Complex
Carbohydrates and lipids.
ja
Bonds in Biomolecules
1. Covalent bond: Formed between two atoms by
electron-sharing (strong bond).
Types:
a. All bonds that form
the small molecules.
Methane gas
notes
The easily formation
and breakdown
of
Hydrogen bonds are extremely important
be
considered
in water and DNA
Vanderwatsand hydrophobic interaction can
Vanderwals
there is
a
movement
occurs in all types
natural weak attraction
of atoms
between
regardless
of their charge
atoms resulting fromthe elliptical
of electrons around the nucleus
zwitterion is a compound that does not have an
aggregate electrical charge, but includes dif ferent
positively and negatively charged sections.
similar
b. Peptide bond: Joins amino acids in proteins. Form
between the carboxyl group of an amino acid and the
amino group of a second, during translation process.
carotid
amino
: Between two
cysteine amino acids.
stratum and contribute
helpstostabilize protein
in it's funition
d. Phosphodiester bond:
Between sugar and phosphate
group, in DNA and RNA.
e. Glycosidic bond: Joins sugars in complex carbohydrates.
f. Ester bonds: Forms lipids.
2. Hydrogen bond: A weak bond between a hydrogen
atom (bound to an electronegative atom like N, O) and an
electronegative atom.
Hydrogen bonds can be formed and broken easily.
Hydrogen bonds between water molecules
Hydrogen bonds within a protein chain
covalent
3. Ionic bond: Bonding oppositely charged ions. There is a
complete transfer of an electron.
4. van der Waals
A weak attractive force
between atoms or
nonpolar molecules
arising from a brief shift
of orbital electrons to
one side of one atom,
creating a similar shift in
adjacent atoms or
molecules.
5. Hydrophobic interactions: The tendency of nonpolar substances to
aggregate in an aqueous solution and exclude water molecules.
Hydrophobic interaction is the main cause for
protein folding.
Non-polar amino acids tend to “hide” away from
water molecules.
Phospholipid molecules arranging
themselves to form the typical double layer
of biological membranes
Bonds that
keep 3D
structure
in proteins
• Water is the solution of life.
• About 75-85% of the cell is water. Exceptions: Bone and
enamel.
• Extracellular water includes plasma and interstitial water.
• Essential for metabolic activity, removes waste from the cell,
and keeps cell’s temperature stable.
• Dissolves most biological molecules. Biomolecules cannot
function without interacting with water.
What is special about water?
1. Water is a highly polar molecule. It binds to
negatively and positively charged groups.
• Water dissolves polar and ionic materials.
Hydrophilic, Hydrophobic & Amphipathic
• Molecules that can
interact with water via
hydrogen bonds are
hydrophilic.
• Non-polar and noncharged molecules are
insoluble in water;
they are hydrophobic.
• Molecules that have
both hydrophilic and
hydrophobic
properties are said to
be amphipathic.
The dielectric constant (the ionization of molecules in a
solvent) of water is very high.
ions
those
water
means
in
separate
Na+
Cl-
When any substance dissolves in water, every molecules of that
substance is surrounded by several water molecules.
the
largerhigher
the the
molecule
mole
it
surround
water
the to
need
A protein molecule dissolved in water.
2. Water molecules link (to each
other and to other molecule)
through hydrogen bonds.
• Hydrogen bonding provides water
with characteristics like having high
boiling point, high surface tension,
and less density when frozen.
• Water molecules are rapidly making
and breaking hydrogen bonds.
Therefore substances move through
water, and water pass through
channels in cellular membranes.
Cell Ions
• The cytosol has a high [K+] ions and a low [Na+] ions.
Outside the cell these concentrations are opposite.
• There are also Ca+2, Cl-2, Mg+2, phosphate, bicarbonate,
amino acids ions.
• The difference in ion concentrations on both sides of
cell membranes, is critical for osmosis regulation and
cell signaling.
pH and Buffers
• Solutions are either neutral, acidic or
of
basic, based on the [H+]. conc
ions
• pH is a value used to indicate hydrogen
ion concentration
pH= -log10[H+]
• A solution of a pH higher than 7 is basic
(low [H+] and high [OH-]) ,and lower
than 7 is acidic (High [H+]), whereas 7 is
neutral.
• Most biological solutions are neutral.
pH in living systems
Compartment
pH
Gastric acid
0.7
Lysosomes
4.5
Urine
6.0
Neutral H2O at 37 °C
6.81
Cytosol
7.2
Cerebrospinal fluid (CSF) 7.3
Blood
7.34 – 7.45
Mitochondrial matrix
7.5
Pancreas secretions
8.1
• In cells, and the body, as a result
of continuous biochemical
processes, pH is bound to change.
• The pH of a solution will affect the
charge on biological molecules,
therefore their structure and
function, and ultimately all
biological processes.
• Therefore, keeping pH relatively
constant is very important, and
multicellular organisms achieve
this by using buffers.
pH differs at different cell compartments.
For your information only
Acid Base Reaction
• An acid is a substance that can donate protons (H+) and
a base is a substance that can accept protons.
• Many of the compounds produced in the cell and
dissolved in water contain chemical groups that act as
acids or bases.
Acid-base reaction: HA + H2O ↔ H3O+ + ADissociation constant (K) of this reaction: K=[H3O+][A-]
/ [HA][H2O]
ofproduct
ofreactants
Collective sons
conc
• K=[H+][A-] / [HA]
(cancelling the H2O)
is the tendency of an
acid to lose a proton.
Ka = [H+] [A-]/[HA]
➢[A−] is the concentration of the conjugate base.
➢[HA] is the concentration of the acid.
• According to their dissociation constant, acids are
classified as weak or strong acids.
• Almost all the molecules of a strong acid dissociate and release
their hydrogen ions.
• For example, HCl in water dissociates into H+ and Cl- ions so
that there are no molecules of HCl remaining.
• A mall percentage of the total molecules of a weak acid
dissociate when dissolved in water.
• Weak acids and their conjugate bases; are very important
biologically.
• Example of weak acid: Acetic acid (CH3COOH) present in many
biological systems CH3COOH
CH3COO- + H+
(HA)
(A-)
Ka values are usually converted to pKa values pKa = -log Ka
pKa is the pH at which 50% dissociation occurs.
Weak acids have higher pKa compared to strong acids.
There are also strong and weak bases.
In an aqueous environment, weak acids and bases exist
either in an
form or in an ionized form. Ionized
molecules are unable to penetrate cell membranes
because they are hydrophilic and poorly lipid soluble.
Unionized molecules are lipid soluble and can diffuse
across cell membranes.
The majority of medicines are weak acids or weak bases.
Drug absorption is determined by the drug’s
physicochemical properties, formulation, and route of
administration.
The degree of ionization of drugs is determined by their
pKa and the pH of the surrounding.
In the stomach, weak acids and bases are highly
protonated. At this site, the non-ionized form of weak acids
and the ionized form of weak bases will predominate.
Hence, weak acids are more readily absorbed from the
stomach than are weak bases.
Buffers
• Adding acids or bases to a neutral solution makes is acidic or
basic, respectfully.
• A buffer solution is one that resists small additions of strong
acid or strong base.
• A buffer consists of a weak acid and its conjugate base (or a
weak base and conjugate acid).
• A buffer has its greatest buffering capacity in the pH range
near its pKa.
• Titration curve shape is described by the
: pH = pKa + log [A-] / [HA]
The middle of the
curve is a flat region
where the addition
of acid or alkali only
results in a small
change in pH. This is
known as the region
of buffering.
In this region the
concentration of
ethanoate ion and
ethanoic acid is
appeared
similar.
Titration curve for ethanoic acid, the flat region is the Region of
Buffering, where addition of Acid or base causes only a small change
in the pH.
Biological Buffers
Maintaining body fluid pH,
the human body uses:
• Bicarbonate buffer system
controls the pH of blood of
air-breathing animals at 7.4
• Phosphate buffer system,
maintains the pH of
mammal cells at an average
of 7.2
• Amino acids and proteins.
• Amino acids are the basic building units of proteins.
• They also form short peptides, and exist as single molecules
and have several functions.
• An amino acid can act as either an acid or a base (ampholyte).
• Some amino acids are very soluble in water and some are
soluble in organic solvent.
The zwitterionic form (dipolar ion)
of the α-amino acids that occurs
at physiological pH values.
Amino Acid Classification
• Amino acids are most commonly
classified by the chemical nature of
their R group.
• The most common way to do this is
to classify them according to their
polarity.
• Amino acids can also be classified in
other ways. For example the
aromatic and aliphatic amino acids.
i
3D
structure
of some
standard
amino
acids
Glycine
Aspartate
Methionine
Tryptophan
Acid – Base Properties of amino acids
• Amino acids act as both weak acids and weak bases.
• The amino and carboxyl groups, and some of the R
groups can gain or lose protons.
• Amino acids that lack an ionisable R group exist as
zwitterions when dissolved in water at pH 7.
• The relative amount of the zwitterion, the fully
protonated or fully deprotonated forms are dependent
upon pH.
• This will affect the amino acids and proteins’ structure.
Amino acid titration curve
• The titration curve is of an amino
acid in an alkaline solution. Acid is
added gradually and the change in
pH of the amino acid solution is
recorded.
• At two regions, glycine shows
buffering capacity: pKa 2.34 (the
carboxyl group) and pKa 9.6 (the
amino group).
• The pI of glycine is the middle
point between the two pKas.
t
afar
The table and
image are only for
your information.
The 20 standard amino acids
Glycine, Alanine, Valine, Leucine, Isoleucine,
Proline, Methionine, Cysteine, Serine, Threonine,
Asparagine, Glutamine, Tyrosine, Phenlyalanine,
Tryptophan, Lysine, Arginine, Histidine, Aspartic
acid & Glutamic acid.
• They are they called Standard amino acids
because they are the only ones that are coded for
on genes.
everyprotein starts with Methionine
Glycine isthesmallest amino acid
Tryptophan is thebiggest amino acid
Essential and non-essential amino acids
Essential amino acids are those that the human
body cannot make, and therefore must be
obtained through the diet.
Plants and bacteria produce the essential amino
acids.
Non-essential amino acids are synthesized in the
human body.
Non-standard amino acids
• Amino acids that do not have codes on genes.
• Most are synthesized by the modification of standard a.a., after
protein synthesis, in the process of
.
• Like standard a.a., they exist as units of proteins, and as single
amino acids.
Examples:
• Hydroxyproline and hydroxylysine exist in collagen.
• γ-Carboxyglutamic acid in blood clotting proteins.
• Dopamine a neurotransmitter.
Amino acids Functions
1. Building units of proteins.
2. Messengers in cell- cell communication:
a. Neurotransmitters: Glycine, Glutamic acid, γ-aminobutyric acid, &
dopamine.
b. Paracrine signaling:
is important in allergic reactions.
c. As hormones:
is a thyroid hormone stimulating metabolism.
3. Important for metabolic processes:
• Citrulline and ornithine are intermediate in urea biosynthesis.
• In synthesis of nucleotides.
4. Participate in the cell’s buffering system
5. Some amino acids have protective functions in plants.
Peptides
• Dipeptides (2 a.a.), tripeptides (3 a.a.) and oligopeptides (3-10 a.a.).
• Peptides typically function as hormones and signaling molecules.
Some examples:
Oxytocin: A posterior pituitary hormone; causes uterine
contraction.
Bradykinin: Inhibits inflammation
Glutathione: Antioxidant, Cell division regulation, DNA repair, amino
acid transport, and many other functions.
Glucagon: A hormone that prevents blood glucose levels from
dropping too much.
Proteins are the functioning molecules in all
organisms.
They also make the structure of most of the body.
Proteins are the product of gene expression.
Our traits are either proteins or they are the result
of proteins action.
Your skin, eyes, hair, bones, blood, etc., all are composed entirely or
mostly of proteins.
Every action in the body, from transport, to receiving or sending signals,
to enzymatic reactions, to DNA replication and RNA synthesis, etc., are
done by proteins. This is true for all organisms.
• Proteins are usually composed of more than 50 amino acids, and
one or more polypeptides arranged in a biologically functional way.
• The 20 standard amino acids (and non standard a.a.) are like letters,
when linked in different ways they make different words, allowing
them to make unlimited types of words (proteins).
• Each protein has a unique molecular weight (measured in Daltons
(Da) or Kilo Daltons KDa), usually greater than 5000 Da.
• Show great diversity in structure, and therefore perform a wide
range of biological functions.
• To understand protein function we must understand protein
structure.
Isoelectric Point (pI)
• The isoelectric point (pI) is the pH at which a protein
has no overall net charge.
• Acidic proteins contain many negatively charged
amino acids and have a low pI
• Basic proteins contain many positively charged
amino acids and have a high pI
Protein functions
• They function as enzymes (Lysozyme).
• Transport and store biologically important substances
such as metal ions, O2, glucose, lipids and other
molecules (haemoglobin, ferritin).
• Generating mechanical motion: Protein fibers for
muscle contraction (actin & myosin), separating
chromosomes during cell division (microtubules), and
other functions.
• Protection: The proteins of the immune system, like the
immunoglobulins, are essential for biological defence
system in higher animals.
• Providing strength and structure: Proteins like collagen,
provide bones, tendons and ligaments with their
characteristic tensile strength.
• Transport across cell membranes: Proteins like Ion
channels and carrier proteins are responsible for the
movement of ions and other molecules across biological
membranes.
: Proteins receptors are responsible for
receiving different signals involved in communication
between cells.
Example: Opsin receptor proteins in the retinal cells of the
eye, receive light and are responsible for vision.
• Some
are proteins: Insulin and somatotropin
(growth hormone).
: Responsible for tissue adhesion.
• Participation in cell buffering.
Lysozyme
Hemoglobin
Ferritin
An Ion Channel
Adhesion proteins
An Immunoglobulin
Opsin
Insulin
DNA & RNA
DNA: Deoxyribonucleic Acid: DNA composes the genetic
information in all cellular life.
RNA: Ribonucleic Acid
• Messenger RNA (mRNA): Copy information for protein synthesis.
• Transfer RNA (tRNA): Delivers amino acids to ribosomes during
protein synthesis.
• Ribosomal RNA (rRNA): Part of ribosomes; functions in protein
synthesis.
• Other types have enzymatic and other functions.
• Made of nucleotide units.
Each nucleotide composed
of: A nitrogen base, sugar
(deoxyribose or ribose) and
a phosphate group.
• Nucleic acids are acidic
(due to the PO4- groups).
• RNA differs in structure
from DNA in: Strand (one),
sugar (ribose), and one of
the nitrogen bases (uracil).
Carbohydrates
• Energy source for the cell.
• Provide structural support to many organisms
• Part of glycoproteins and glycolipids (important in cell
communication).
• Monosaccharides: Linear or ring shaped.
• Glucose is made in plants from CO2 and H2O. Broken down
in cellular respiration to produce ATP.
• Glycosidic bond: Is the covalent bond that links
monosacchraides together.
• Disaccharides: Lactose, Maltose, Sucrose.
• Oligosaccharides: 3-10 sugar units. Normally linked
to lipids or to proteins. Functions: Cell recognition
and generally important role in immune response.
• Polysaccharides: Starch is the stored form of sugars
in plants. Glycogen is the storage form of glucose in
animals. Cellulose makes plant cell walls. Chitin
exists in the exoskeleton or arthropods (insects,
spiders and crabs).
Lipids
•
•
•
•
•
•
•
Hydrophobic molecules.
Fats, oils, waxes, phospholipids & steroids.
Long-term energy source.
Form cell and organelle membranes.
Provide insulation from the environment for plants and animals.
Steroid hormones are lipids.
Saturated lipids: Contain no double bond in their structures. Solid at
room temperature.
• Unsaturated lipids: Contain double bonds in their structures. Liquid
at room temperature.
• Fats and oils are made up of fatty acids and glycerol.
• Triglycerides are lipids composed of glycerol and three fatty
acids. They are the main constituents of body fat in humans
and other vertebrates.