Occupational Therapy and Nucleotides

1. Occupational Therapy
Nucleotides

3. Nucleotides
Nucleotides play key roles in nearly all biochemical processes,
including the following:
- 1. Nucleic acid synthesis: Nucleotides are the activated
precursors of DNA and RNA.
- 2. Energy transfer: ATP is used as a universal currency of
energy in biological systems and GTP is utilized in many systems
involved in movements or conformational changes of
macromolecules.
- 3. Coenzymes: Adenine nucleotides are components of some
major coenzymes.

4. Nucleotides
Nucleotides play key roles in nearly all biochemical processes,
including the following:
- 4. Metabolism: Nucleotide derivatives are activated intermediates
in many biosynthetic reactions, and they also serve as mediators
to regulate metabolism.
- 5. Signaling processes: Signal transduction processes often
involve non-enzymatic second messengers, including cyclic
nucleotides (cAMP, cGMP, cyclic di-GMP). These processes
allow cells to communicate with their environment (both internal
and external) and with other cells, modifying cellular activity
and gene expression.

5. Nucleotides
- Nucleotides consist of a nitrogen-containing base, a five-carbon
sugar and one or more phosphate groups.
- Cells contain many types of nucleotides, which are in constant
flux between free and polymeric states.
- Nucleotides play central roles in many cellular processes,
including metabolic regulation and the storage and utilization of
genetic information.
- The levels of nucleotides in cells are regulated efficiently due to
the small pools of free nucleotides, with an exception being
adenosine-5′ -triphosphate, which is at higher concentrations
due to its role as the universal currency of energy

7. Nucleotides
- Within cells, ribonucleotides are synthesized from simple
building blocks or they are obtained via the recycling of
preformed bases.
- Different types of cells have striking variations in their
nucleotide composition as these are linked to the rate of cell
growth; in mammals, the amounts of nucleotides and nucleic
acids as a proportion of cell weight vary from approximately 1%
in muscle to 15–40% in thymus gland and sperm cells
- Nucleotides play central roles in many cellular processes,
including metabolic regulation and the storage and expression
of genetic information

8. All nucleotides have three fundamental components
- Base: Also referred to as heterocycles, these nitrogen-containing
ring compounds are derivatives of purine or pyrimidine.
- The atoms within the purine/pyrimidine rings have a common
arrangement and they are given the same number in different
nucleotides.
- A variety of chemical groups can be bonded at different positions
to the ring constituents. Although one structure predominates
for each base, tautomeric forms occur in minor amounts

9. All nucleotides have three fundamental components
- Sugar: A five-carbon sugar, usually ribose, is linked to the base.
- Each carbon atom is numbered and, to allow their distinction
from atoms in the base, the number is followed by a prime mark:
thus, ribose has five carbon atoms, numbered 1′ to 5′
- The sugars are locked into a five-membered furanose ring by the
bond from C1′ of the sugar to the base

10. All nucleotides have three fundamental components
- Phosphate ester: Phosphate groups are attached to the sugar by
ester linkages, with the most common site of esterification in
natural compounds being via the hydroxyl at the C5′ position.
- Typically, one, two or three phosphates are joined, producing
mono-, di- and triphosphates, respectively

11. Nucleotides Overview
- Store and transmit genetic info and energy
A single nucleotide consists of 3 parts
- a sugar (2 possibilities)
- 1 or more phosphate groups
- 1 of 5 nitrogenous bases
- Sugars = ribose or deoxyribose(=ribose minus 1 Oxygen)
2 types of Nitrogenous bases
- 1. Purines- have a double ring structure- adenine (A),
guanine(G)
- 2. Pyrimidines-single ring structure- cytosine (C), thymine (T),
uracil (U)

14. Single Nucleotides
- Smallest nucleotides include- Adenosine triphosphate (ATP),
Adenosine diphosphate (ADP)= energy transferring compounds
- cAMP- (cyclic Adenosine monophosphate) transfer of signals
between ECF and cell
- Nicotinamide adenine dinucleotide (NAD) and Flavin adenine
dinucleotide (FAD)- energy transferring nucleotides

15. Nucleic Acids = nucleotide polymers
Nucleotides linked into long chains
- Sugar of one links to phosphate group of next
- Nitrogenous bases extend to the side of the chain
DNA and RNA- store and transmit genetic info
- DNA=deoxyribonucleic acid
- RNA=ribonucleic acid

21. Deoxyribonucleic acid (DNA) Overview
- Bases: Adenine, Guanine, Cytosine, Thymine (Pairing: A-T, G-
C)
- Two chains of nucleotides in a double helix molecules
- Hydrogen bonds between complementary base pairs hold
molecule together
- Function: storage of genetic information

24. Ribonucleic acid (RNA) Overview
- Bases: Adenine, Guanine, Cytosine, Uracil (Pairing: A-U, G-C)
- One chain of nucleotides
- Types: ribosomal RNA (rRNA), messenger RNA (mRNA),
transfer RNA (tRNA)
- Function: translate genetic information into protein synthesis.

25. Ribonucleic acid (RNA)

26. Protein Interactions
Most soluble proteins fall into one of 7 broad categories
1. Enzymes
- Speed up chemical reactions
2. Membrane Transporters
- Move substances in and out of cells via channels in membrane
or binding molecules and carrying them thru
3. Signal Molecules
- Hormones etc.
4. Receptors
- Bind signal molecules and initiate cellular responses

27. Protein Interactions
Most soluble proteins fall into one of 7 broad categories
5. Binding proteins
- Mostly in ECF bind and transport molecules through body e.g.;
Hb, LDL- cholesterol transport
6. Regulatory proteins
- Turn cell processes on/off or up/down e.g.; transcription
factors- bind DNA for gene expression and protein synthesis
7. Immunoglobulins
- Extracellular immune proteins = antibodies- immune protection

29. Common Features of Soluble Proteins
- All bind to other molecules non-covalently
- Binding site = location on protein molecule where binding takes
place
- Binding of a molecule to a protein binding site can initiate a
process
- Ligand = any molecule that binds to another molecule
- Substrate = ligand that binds to an enzyme or membrane
transporter
- Protein signal molecules and transcription factors are ligands

30. Induced-fit model of protein – Ligand binding

31. Induced-fit model of protein – Ligand binding
- For binding to occur the binding site and the ligand must be
compatible.
- In protein binding, when ligand and binding site come close,
non-covalent interactions allow the 2 molecules to bind.
- The binding site and ligand don’t have to fit exactly, they interact
via H-bonds and van der waals forces, then the binding site
changes shape(conformational change) to fit more closely to the
ligand

32. Binding site properties
Binding sites exhibit the following 4 properties
1. Specificity
2. Affinity
3. Competition
4. Saturation
1. Protein Specificity = ability of protein to bind a certain ligand
or groups of ligands
- Some are very specific, some will bind whole groups
- E.g.; Enzymes- peptidases will break apart any polypeptides
peptide bonds regardless of AA ( not very specific)
- Amino peptidases will only bind to the terminal end of a peptide
chain (specific)

33. Binding site properties
2. Affinity = degree to which protein is attracted to ligand
- Higher affinity = more likely to bind
- Binding can be reversible P + L ↔ PL
- Reversible reactions reach a state of equilibrium where rate of
binding = rate of unbinding(dissociation) A + B ↔ C + D

34. Binding reactions obey the law of mass action

35. Law of mass action
- In the body, concentrations of ligands or proteins are constantly
changing
- Protein–ligand binding reactions are often reversible
- Law of Mass Action states- when a reaction is at equilibrium, the
ratio of the concentration of products to substrates is always the
same. If the ratio is disturbed by adding or removing a product
or substrate, the reaction will shift in the direction that restores
equilibrium.
- If you add extra protein or ligand, the reaction will go in the
direction of increased binding of protein to ligand, until
equilibrium is restored

36. Law of mass action
- If you take away protein or ligand, the reaction will go in the
reverse direction where the protein-ligand complex will unbind
until equilibrium is restored.

37. Binding site properties
3. Competition
- Related ligands compete for binding sites
- Agonist= a ligand that mimics another ligands action.
- E.g.; nicotine mimics activity of ACh by binding to same receptor
- Drugs can be designed to be agonists
- A competitive antagonist = an inhibitor- will bind to a protein
and decrease its activity

38. Modulation of Binding Affinity
- A protein’s affinity for a ligand is not always constant as
chemical and physical factors can alter or modulate binding
affinity. Binding affinity can be removed altogether.
- Some proteins require activation before they have a functioning
binding site
- Modulator = a factor that influences either protein binding or
protein activity

40. Factors that alter protein binding
- Can be chemical or physical
- Isoforms = closely related proteins with similar functions but
different affinities for ligand

41. Activation
- Some proteins are inactive when synthesized in the cell.
- Proteolytic Activation = In order for these proteins to become
active, enzymes must chop off certain parts of the protein
molecule
- Inactive forms of proteins often have the prefix ‘pro’ or suffix
‘ogen’ eg; proinsulin is activated to form insulin, trypsinogen is
activated to form trypsin

42. Activation Co-Factors
- Some proteins require the presence of cofactors to activate
binding sites
- Cofactors are ions or small functional groups that must attach to
binding site before the ligand will bind
E.g.; Mg2+ ,Ca2+ , Fe2+
- Many enzymes can’t function without cofactors

43. Modulation
2 Basic Mechanisms- Modulator either
- 1. Changes ability of ligand to bind to binding site
- 2. Changes protein’s activity or ability to create a response
- Factors including temperature, pH and molecules that interact
with the protein, can all modulate protein activity

44. Chemical Modulators = molecules that bind covalently or non
covalently to proteins and alter their binding ability
- Can activate or enhance ligand binding, decrease binding ability,
or completely inactivate protein binding ability (inactivation may
be reversible or irreversible)
- Antagonists= inhibitors- bind to a protein and decrease its
activity
Competitive inhibitors= reversible antagonists
- They compete with the usual ligand for that binding site
- The degree of inhibition depends on the relative concentrations
of the ligand and inhibitor as well as the different affinities of
ligand and inhibitor for the binding site.

45. Competitive inhibitors= reversible antagonists
- Competitive inhibitors can be displaced from the binding site by
increasing the concentration of the usual ligand
Irreversible Antagonists= bind tightly to the protein and can’t be
displaced
- Some powerful drugs act in this way

46. Allosteric Modulation

47. Allosteric Modulators
- Can be activators or antagonists
- Bind reversibly to protein at a regulatory site away from the
binding site and this causes a change in shape of the binding site
- Allosteric inhibitors- decrease affinity of binding site for ligand
and decrease protein activity
- Allosteric activators- increase protein ligand binding and
enhance protein activity

48. Covalent Modulators = atoms or functional groups bind
covalently to protein and alter its properties
- Can activate or inhibit
E.g.; Phosphorylation
- Very common Phosphate group binds to protein
- Can activate or inactivate

49. Physical Modulators
- pH or Temperature
- Small changes act as modulators to increase or decrease activity
- A critical point is reached at which non-covalent bonds are
disrupted and tertiary conformation is lost = denatured (protein
loses shape and activity e.g.; cooked egg white. This is usually
not reversible hence body closely regulates pH and Temp

51. Regulation of Proteins
- The body regulates the amount of proteins in cells
- Up-regulation = complex signaling pathways direct cells to make
new proteins
- Down-regulation = proteins are removed
- Cells regulate protein concentration to control physiological
processes.
- Increased protein concentration means increased reaction rate
and vice versa

54. Saturation
- If protein concentration is constant then ligand concentration
determines reaction rate.
- At low ligand concentration response rate is directly
proportional to concentration
- Once the ligand molecules reach a certain level the protein will
have no more free binding sites so reaction rate reaches its
maximal value = saturation