BIO PHAY1003

Outline cell theory

All living organisms are composed of one or more units called cells

Each cell is capable of maintaining its own vitality independently

Cells can only arise form other cells

Viruses are not cells.

Viruses are cells

Cells reproduce by way of binary fission

Cells contain DNA, found specifically in the chromosome and RNA found in the cell nucleus & cytoplasm

All cells are basically the same in chemical composition in organisms of similar species

Prokaryotes

Large sizes due to central vacuole (responsible for growth)

Limited by efficient metabolism

Limited by surface area to volume ratio

Eukaryotic animal cells

Large sizes due to central vacuole (responsible for growth)

Limited by efficient metabolism

Limited by surface area to volume ratio

Plant cells (eukaryotic)

Large sizes due to central vacuole (responsible for growth)

Limited by efficient metabolism

Limited by surface area to volume ratio

What are viruses/virions...

Tiny particles visible through electron microscope

Tiny particles visible through light microscope

Cells

Contain genetic information in the form of DNA/RNA

Contain protein coat (capsid) which surrounds/protects genetic material

Non-infectious agent

In some cases envelope of lipids surrounds capsid when virus is outside of cell

Are cells because they carry genetic material, reproduce, & evolve through natural selection

Are not cells because they lack key characteristics (such as cell structure)

Viruses do not contain their own

Viruses only replicate by

Viruses multiply by

Virus particles released from the cell can cause

Viral infections in animals may cause

Artificial immunity can be induced by

Cells are

Surrounded by a plasma membrane with a viscous fluid (cytoplasm)

Eg bacteria

Units of which bodies of living organisms are made

Plants/animal clels

Every living cell is

Surrounded by a plasma membrane with a viscous fluid (cytoplasm)

Eg bacteria

Units of which bodies of living organisms are made

Plants/animal clels

Prokaryotic cells are

Surrounded by a plasma membrane with a viscous fluid (cytoplasm)

Eg bacteria

Units of which bodies of living organisms are made

Plants/animal clels

Eukaryotic cells are

Surrounded by a plasma membrane with a viscous fluid (cytoplasm)

Eg bacteria

Units of which bodies of living organisms are made

Plants/animal clels

Eukaryotic cells are simpler in their structure than prokaryotic cells

True

False

Bacteria cells major shapes

Bacillus (coils) spirilla (round) coccus (coils)

Coccus (round) bacillus (rods) spirilla (coils

Bacillus (round) spirilla (coils) coccus (rods)

Spirilla (round) coccus (rods) bacillus (coils)

Eukaryotic cells

Basic units of animals and plants

Not single celled types and fungi

And single celled types & fungi

Plant cells generally have large

Proteins and other lipids

Double layer of phospholipid

Chlorophyll for photosynthesis to trap sunlight => carbs.

Fluid filled vacuoles.

Cell walls. Animal cells do not.

Dynamic structures controlling contents of compartments they enclose

Plant cells have

Proteins and other lipids

Double layer of phospholipid

Chlorophyll for photosynthesis to trap sunlight => carbs.

Fluid filled vacuoles.

Cell walls. Animal cells do not.

Dynamic structures controlling contents of compartments they enclose

Plant cells have chloroplasts that contain

Proteins and other lipids

Double layer of phospholipid

Chlorophyll for photosynthesis to trap sunlight => carbs.

Fluid filled vacuoles.

Cell walls. Animal cells do not.

Dynamic structures controlling contents of compartments they enclose

Cell membranes consist of a

Proteins and other lipids

Double layer of phospholipid

Chlorophyll for photosynthesis to trap sunlight => carbs.

Fluid filled vacuoles.

Cell walls. Animal cells do not.

Dynamic structures controlling contents of compartments they enclose

Embedded in fluid mosaic are

Proteins and other lipids

Double layer of phospholipid

Chlorophyll for photosynthesis to trap sunlight => carbs.

Fluid filled vacuoles.

Cell walls. Animal cells do not.

Dynamic structures controlling contents of compartments they enclose

Membranes are not passive barriers but

Proteins and other lipids

Double layer of phospholipid

Chlorophyll for photosynthesis to trap sunlight => carbs.

Fluid filled vacuoles.

Cell walls. Animal cells do not.

Dynamic structures controlling contents of compartments they enclose

Plasma membrane

Same as outer membrane

Controls passage of materials into and out of cell

Receives messages that regulate behaviour of cell

Single layer phospholipid

3D network of membranes extending throughout cell

Rough: covered on cytoplasmic side with ...

Large surface area

Site of protein synthesis

All of the above

Golgi apparatus

3D network of membranes

Site of protein synthesis

Specialised region of membranes enclosing cisternae from which vesicles arise

Carbs added to proteins coming from ER to form glycoproteins

Where glycoproteins secreted at cell surface/sent to other parts

Where parts are rough or smooth

Small surface area

Mitochondria

Small elongated bodies

Electron micrograph: internal structure

Seen clearly through light microscope

Internal space/matrix has enzymes and some DNA

Produce glucose

Produce ATP to carry energy to processes in cell

Useful for muscle contraction/active transport/protein synthesis

Largest organelle within cell

Nucleus

Largest of organelles

Contains chloroplasts

Is where protein synthesis takes place

Not present in most cells

Found in prokaryotic cells

Encloses nuclear membrane

Double membrane surrounds it with pores (seen via electron micrograph)

Contains DNA attached to histones => chromatin

Groups of cells are organised into

Organs

Tissues

Self-contained part of organism (group of tissues) with a specific vital function

Respiratory, immune, circulatory, digestive

Large mass if specialized cells and their products making up part of an organism for a specific function

Smallest structural and functional unit of an organism

Organ systems

Group of organs that work together to perform one or more function

Epithelial, muscle, connective and nervous

Tissue examples:

Organs

Tissues

Self-contained part of organism (group of tissues) with a specific vital function

Respiratory, immune, circulatory, digestive

Large mass if specialized cells and their products making up part of an organism for a specific function

Smallest structural and functional unit of an organism

Organ systems

Group of organs that work together to perform one or more function

Epithelial, muscle, connective and nervous

Tissues are organised into

Organs

Tissues

Self-contained part of organism (group of tissues) with a specific vital function

Respiratory, immune, circulatory, digestive

Large mass if specialized cells and their products making up part of an organism for a specific function

Smallest structural and functional unit of an organism

Organ systems

Group of organs that work together to perform one or more function

Epithelial, muscle, connective and nervous

Organs may be organized into

Organs

Tissues

Self-contained part of organism (group of tissues) with a specific vital function

Respiratory, immune, circulatory, digestive

Large mass if specialized cells and their products making up part of an organism for a specific function

Smallest structural and functional unit of an organism

Organ systems

Group of organs that work together to perform one or more function

Epithelial, muscle, connective and nervous

Organ systems

Organs

Tissues

Self-contained part of organism (group of tissues) with a specific vital function

Respiratory, immune, circulatory, digestive

Large mass if specialized cells and their products making up part of an organism for a specific function

Smallest structural and functional unit of an organism

Organ systems

Group of organs that work together to perform one or more function

Epithelial, muscle, connective and nervous

Cell

Organs

Tissues

Self-contained part of organism (group of tissues) with a specific vital function

Respiratory, immune, circulatory, digestive

Large mass if specialized cells and their products making up part of an organism for a specific function

Smallest structural and functional unit of an organism

Organ systems

Group of organs that work together to perform one or more function

Epithelial, muscle, connective and nervous

Tissue

Organs

Tissues

Self-contained part of organism (group of tissues) with a specific vital function

Respiratory, immune, circulatory, digestive

Large mass if specialized cells and their products making up part of an organism for a specific function

Smallest structural and functional unit of an organism

Organ systems

Group of organs that work together to perform one or more function

Epithelial, muscle, connective and nervous

Organ

Organs

Tissues

Self-contained part of organism (group of tissues) with a specific vital function

Respiratory, immune, circulatory, digestive

Large mass if specialized cells and their products making up part of an organism for a specific function

Smallest structural and functional unit of an organism

Organ systems

Group of organs that work together to perform one or more function

Epithelial, muscle, connective and nervous

Organ system

Organs

Tissues

Self-contained part of organism (group of tissues) with a specific vital function

Respiratory, immune, circulatory, digestive

Large mass if specialized cells and their products making up part of an organism for a specific function

Smallest structural and functional unit of an organism

Organ systems

Group of organs that work together to perform one or more function

Epithelial, muscle, connective and nervous

Mitosis

Two identical daughter cells

Different from parent cells

DNA with histone proteins can be seen as threads = 'chromosomes'

Somatic cell division for growth/produce cells during repair/replacement

Produces half number of chromosomes as original

Produce gametes (Haploids)

4 main stages: Metaphas Interphase Anaphase Prophase

Humans contain

23 chromosomes

46 homologous pairs

23 homologous pairs

46 chromosomes

Before division a cell is

Merged, during the actual active process

Not visible

A granular body with one or more dense nucleoli

In interphase

Chromosomes in interphase are

Merged, during the actual active process

Not visible

A granular body with one or more dense nucleoli

In interphase

In interphase nucleus appears as

Merged, during the actual active process

Not visible

A granular body with one or more dense nucleoli

In interphase

Mitosis has stages which are

Merged, during the actual active process

Not visible

A granular body with one or more dense nucleoli

In interphase

Cell cycle

Largest part of cell cycle

2. Replication of DNA completed and duplication of histone proteins

Total process of growht and division by mitosis

3. Synthesis of organelles such as mitochondria

1. Synthesis of RNA and protein

Interphase

Largest part of cell cycle

2. Replication of DNA completed and duplication of histone proteins

Total process of growht and division by mitosis

3. Synthesis of organelles such as mitochondria

1. Synthesis of RNA and protein

G1 stage

Largest part of cell cycle

2. Replication of DNA completed and duplication of histone proteins

Total process of growht and division by mitosis

3. Synthesis of organelles such as mitochondria

1. Synthesis of RNA and protein

G2 stage

Largest part of cell cycle

2. Replication of DNA completed and duplication of histone proteins

Total process of growht and division by mitosis

3. Synthesis of organelles such as mitochondria

1. Synthesis of RNA and protein

S stage

Largest part of cell cycle

2. Replication of DNA completed and duplication of histone proteins

Total process of growht and division by mitosis

3. Synthesis of organelles such as mitochondria

1. Synthesis of RNA and protein

Cell cycle

Significance of meiosis

Cells produced are gametes

@ fertilisation, form zygote; 2 haploid cells fuse to form once cell

In sexual reproduction resulting organism exactly the same as parents

Cells produced diploids

Gametes have varied combination due to reassortment/recombination

Gametes have varied combination due to linkage analysis

Draw simple diagrams of typical viruses, bacteria, plant cells and animal cells showing the structure as revealed by electron microscopy, including; nucleus, mitochondria, chloroplasts, endoplasmic reticulum, Golgi apparatus, ribosomes, lysosomes, peroxisomes, plasma membrane, vacuoles, cell wall and cytoplasm.

Assign to the structures in objective 1 their major biochemical function.

Distinguish the differences in the structure of bacteria, plant and animal cells.

List at least five characteristics which could be used to distinguish prokaryotic and eukaryotic organisms.

Explain the terms; cell, tissue, organ and organ system

Describe the process of cell division by mitosis in terms of the major events that occur in interphase, prophase, metaphase, anaphase and telophase.

Show how the cell cycle can be divided into G1 phase, S phase, G2 phase, mitosis and cytoplasmic cleavage and represented as a pie-chart.

Describe the major events of meiosis in terms of prophase I, metaphase I, anaphase I, telophase I, followed by prophase II, metaphase II, anaphase II and telophase II.

Glycogen metabolism. Explain glycogen structure of glycogen

Glycogen metabolism roles of certain organs and storage.

Glycogen synthesis.

Glycogen breakdown.

What to kinases do

GDP/GTP?

Energy molecules

Guanosine triphosphate and guanosine diphosphate

Used in glycolysis

Glycogen storage diseases

Type V

McArdle's disease

Muscle unable to perform strenuous exervise

Gets powerful muscle cramps and fatigue

Muscle has abnormal glycogen structure but increased in amount

Genetic defect is presence of glycogen phosphorylase; cannot breakdown G1P to feed into glycolysis via G6P => decreased eneregy production in muscle

Type VI, Hers' deisease; dangerous as patients have glycogen phosphorylase absent from liver. => liver enlargement due to increased glycogen an dhypoglycaemia as they cannot breakdown glycogen to G1P to G6P and release glucose in blood. During fasting; struggle to maintain blood glucose.

Dietary fibre

Promotes gut motility/peristalsis

Insoluble fibre found in whole-wheat, nuts and veg

Soluble fibre in oats, peas, beans and fruis dissolves in water to make gel, slowing food movement

Help lower blood glucose as it slows sugar absorption. Reduce type 2 diabetes risk

Insoluble fibre in oats, peas beans and fruits dissolves in water to make gel, slowing food movement

Soluble fibre found in whole-wheat, nuts and veg

A-1,6 glucosidase

Hydrolysis a-1,6 linkage in glycogen => straight chain

Be used in TCA cycle in pyruvate form

Found on same bifunctional coenzyme as part of single 160,000 Da polypeptide chain

Be converted to glucose by glucose-6-phosphatase and released into bloodstream

Located on lumenal side of smooth ER to convert it to glucose

Phosphoglucomutase step as G-1-P>>>G-6-P

Glycogen breakdown transferase and phosphorylase activity

Hydrolysis a-1,6 linkage in glycogen => straight chain

Be used in TCA cycle in pyruvate form

Found on same bifunctional coenzyme as part of single 160,000 Da polypeptide chain

Be converted to glucose by glucose-6-phosphatase and released into bloodstream

Located on lumenal side of smooth ER to convert it to glucose

Phosphoglucomutase step as G-1-P>>>G-6-P

Glucose -1- phosphate is converted to Glucose - 6- phosphate due to reversal of

Hydrolysis a-1,6 linkage in glycogen => straight chain

Be used in TCA cycle in pyruvate form

Found on same bifunctional coenzyme as part of single 160,000 Da polypeptide chain

Be converted to glucose by glucose-6-phosphatase and released into bloodstream

Located on lumenal side of smooth ER to convert it to glucose

Phosphoglucomutase step as G-1-P>>>G-6-P

In skeletal muscle G-6-P will

Hydrolysis a-1,6 linkage in glycogen => straight chain

Be used in TCA cycle in pyruvate form

Found on same bifunctional coenzyme as part of single 160,000 Da polypeptide chain

Be converted to glucose by glucose-6-phosphatase and released into bloodstream

Located on lumenal side of smooth ER to convert it to glucose

Phosphoglucomutase step as G-1-P>>>G-6-P

In liver G-6-P will

Hydrolysis a-1,6 linkage in glycogen => straight chain

Be used in TCA cycle in pyruvate form

Found on same bifunctional coenzyme as part of single 160,000 Da polypeptide chain

Be converted to glucose by glucose-6-phosphatase and released into bloodstream

Located on lumenal side of smooth ER to convert it to glucose

Phosphoglucomutase step as G-1-P>>>G-6-P

G-6-P cannot diffuse out of cells therefore liver has enzyme

Hydrolysis a-1,6 linkage in glycogen => straight chain

Be used in TCA cycle in pyruvate form

Found on same bifunctional coenzyme as part of single 160,000 Da polypeptide chain

Be converted to glucose by glucose-6-phosphatase and released into bloodstream

Located on lumenal side of smooth ER to convert it to glucose

Phosphoglucomutase step as G-1-P>>>G-6-P

Phosphorolysis in that it is reversible in vitro (test tube) but in reality it is irreversible because

[Pi] is higher than [glucose 1 phosphate]

Active transport occurs using ATP to force reaction forward

More energetically favourable; formation of phosphorylated glucose with using energy ATP.

More energetically favourable; formation of phosphorylated glucose w/o using energy - ATP.

Phosphate group is energetically stabilised by resonance, but not the case when in ATP

[glucose 1 phosphate] is higher than [Pi]

Anabolic rxns

Catabolic rxns

Rxns not requiring oxygen (anaerobic)

Rxns requiring oxygen (aerobic)

Camdekat

Sanger sequencing method

Three aspects of chem of aa understand/:

Ionization

Structural characteristics

Optical isomerism

Isoelectric point

Ph where aa no net charge

PI = pK1+pk2

Ph where no charges exist

PI = (pk1+pk2)/2

Apart from ____ all aa contain a chiral centre, some more than 1

Glycine

Cysteine

Simplest aa

In biochem use system of relative configuration because

It gives the shape of the molecule

All molecules designated L relate to L-glyceraldehyde

It gives absolute configuration

precise arrangement of substituents at a stereogenic center

Arrangement of atoms in an optically active molecule, based on chemical interconversion from or to a known compound

There is no way of knowing just by looking at a structure whether the assignment of (+) or (-) is correlated to a particular isomer, R or S

Imino

phenylalanine (phe), tyrosine (tyr), tryptophan (trp)

Asparagine (asn), glutamine (gln)

lysine (lys), arginine (arg), histidine (his)

Serine (ser), threonine (thr)

glycine (gly), alanine (ala), valine (val), leucine (leu), isoleucine (ile).

Proline (pro)

aspartic acid (asp), glutamic acid(glu)

Cysteine (cys), methionine (met)

Sulphur

phenylalanine (phe), tyrosine (tyr), tryptophan (trp)

Asparagine (asn), glutamine (gln)

lysine (lys), arginine (arg), histidine (his)

Serine (ser), threonine (thr)

glycine (gly), alanine (ala), valine (val), leucine (leu), isoleucine (ile).

Proline (pro)

aspartic acid (asp), glutamic acid(glu)

Cysteine (cys), methionine (met)

Aliphatic

phenylalanine (phe), tyrosine (tyr), tryptophan (trp)

Asparagine (asn), glutamine (gln)

lysine (lys), arginine (arg), histidine (his)

Serine (ser), threonine (thr)

glycine (gly), alanine (ala), valine (val), leucine (leu), isoleucine (ile).

Proline (pro)

aspartic acid (asp), glutamic acid(glu)

Cysteine (cys), methionine (met)

Hydroxyl

phenylalanine (phe), tyrosine (tyr), tryptophan (trp)

Asparagine (asn), glutamine (gln)

lysine (lys), arginine (arg), histidine (his)

Serine (ser), threonine (thr)

glycine (gly), alanine (ala), valine (val), leucine (leu), isoleucine (ile).

Proline (pro)

aspartic acid (asp), glutamic acid(glu)

Cysteine (cys), methionine (met)

Amide

phenylalanine (phe), tyrosine (tyr), tryptophan (trp)

Asparagine (asn), glutamine (gln)

lysine (lys), arginine (arg), histidine (his)

Serine (ser), threonine (thr)

glycine (gly), alanine (ala), valine (val), leucine (leu), isoleucine (ile).

Proline (pro)

aspartic acid (asp), glutamic acid(glu)

Cysteine (cys), methionine (met)

Acidic

phenylalanine (phe), tyrosine (tyr), tryptophan (trp)

Asparagine (asn), glutamine (gln)

lysine (lys), arginine (arg), histidine (his)

Serine (ser), threonine (thr)

glycine (gly), alanine (ala), valine (val), leucine (leu), isoleucine (ile).

Proline (pro)

aspartic acid (asp), glutamic acid(glu)

Cysteine (cys), methionine (met)

Aromatic

phenylalanine (phe), tyrosine (tyr), tryptophan (trp)

Asparagine (asn), glutamine (gln)

lysine (lys), arginine (arg), histidine (his)

Serine (ser), threonine (thr)

glycine (gly), alanine (ala), valine (val), leucine (leu), isoleucine (ile).

Proline (pro)

aspartic acid (asp), glutamic acid(glu)

Cysteine (cys), methionine (met)

Basic

phenylalanine (phe), tyrosine (tyr), tryptophan (trp)

Asparagine (asn), glutamine (gln)

lysine (lys), arginine (arg), histidine (his)

Serine (ser), threonine (thr)

glycine (gly), alanine (ala), valine (val), leucine (leu), isoleucine (ile).

Proline (pro)

aspartic acid (asp), glutamic acid(glu)

Cysteine (cys), methionine (met)

Plasma membrane is responsible for

maintaining the internal environment (pH, osmolality, ionic - Na+, K+, Ca2+, Cl- etc.) so that the delicate biochemical machinery can function properly.

control the intake of food and fuel, and to get rid of waste products.

Other water soluble mol/ions selectively transported via channels/pumps/gates formed by transmembrane proteins. In general transport is of two types.

Passive diffusion

Active transport

Neuromuscular blockers do not

Block pain

Cause skeletal muscle paralysis

Consist of depolarising and non-depolarising substances

Sliding filament theory.

Destruction of an enzyme activity by protein denaturation e.g., strong acids or bases etc.

Is not regarded as enz inhibition

Is reversible

Is irreversible

Is regarded as enz inhibition

AChE Enzyme

Factors affecting Enzymes

Nomenclature; Oxidoreductases (or Dehydrogenases)

� transfer functional groups from donor to acceptor

. Pyruvate decarboxylase – break bonds such as C-C, C-O, C-N..

E.g. Alanine racemase – geometric or structural changes within a molecule

E.g. Glutamine synthetase – joins molecules together, forms bonds, requiring ATP energy

Enzyme Commission Number

E.g lactate dehydrogenase – catalyse oxidation and reduction reactions.

S e.g. esterases (acetylcholinesterase), proteases – hydrolysis of C-O, C-N and C-C bonds

Transferases e.g. Aspartate aminotransferase

� transfer functional groups from donor to acceptor

. Pyruvate decarboxylase – break bonds such as C-C, C-O, C-N..

E.g. Alanine racemase – geometric or structural changes within a molecule

E.g. Glutamine synthetase – joins molecules together, forms bonds, requiring ATP energy

Enzyme Commission Number

E.g lactate dehydrogenase – catalyse oxidation and reduction reactions.

S e.g. esterases (acetylcholinesterase), proteases – hydrolysis of C-O, C-N and C-C bonds

Hydrolases e.g. esterases (acetylcholinesterase), proteases

� transfer functional groups from donor to acceptor

. Pyruvate decarboxylase – break bonds such as C-C, C-O, C-N..

E.g. Alanine racemase – geometric or structural changes within a molecule

E.g. Glutamine synthetase – joins molecules together, forms bonds, requiring ATP energy

Enzyme Commission Number

E.g lactate dehydrogenase – catalyse oxidation and reduction reactions.

S e.g. esterases (acetylcholinesterase), proteases – hydrolysis of C-O, C-N and C-C bonds

Lyases

� transfer functional groups from donor to acceptor

. Pyruvate decarboxylase – break bonds such as C-C, C-O, C-N..

E.g. Alanine racemase – geometric or structural changes within a molecule

E.g. Glutamine synthetase – joins molecules together, forms bonds, requiring ATP energy

Enzyme Commission Number

E.g lactate dehydrogenase – catalyse oxidation and reduction reactions.

S e.g. esterases (acetylcholinesterase), proteases – hydrolysis of C-O, C-N and C-C bonds

Isomerases

� transfer functional groups from donor to acceptor

. Pyruvate decarboxylase – break bonds such as C-C, C-O, C-N..

E.g. Alanine racemase – geometric or structural changes within a molecule

E.g. Glutamine synthetase – joins molecules together, forms bonds, requiring ATP energy

Enzyme Commission Number

E.g lactate dehydrogenase – catalyse oxidation and reduction reactions.

S e.g. esterases (acetylcholinesterase), proteases – hydrolysis of C-O, C-N and C-C bonds

Ligases

� transfer functional groups from donor to acceptor

. Pyruvate decarboxylase – break bonds such as C-C, C-O, C-N..

E.g. Alanine racemase – geometric or structural changes within a molecule

E.g. Glutamine synthetase – joins molecules together, forms bonds, requiring ATP energy

Enzyme Commission Number

E.g lactate dehydrogenase – catalyse oxidation and reduction reactions.

S e.g. esterases (acetylcholinesterase), proteases – hydrolysis of C-O, C-N and C-C bonds

Subdivisions in each group according to the exact substrate allow a complete classification, each enzyme with its own

� transfer functional groups from donor to acceptor

. Pyruvate decarboxylase – break bonds such as C-C, C-O, C-N..

E.g. Alanine racemase – geometric or structural changes within a molecule

E.g. Glutamine synthetase – joins molecules together, forms bonds, requiring ATP energy

Enzyme Commission Number

E.g lactate dehydrogenase – catalyse oxidation and reduction reactions.

S e.g. esterases (acetylcholinesterase), proteases – hydrolysis of C-O, C-N and C-C bonds

For a given enzyme, Km is a constant and is thus

Calculating Michaelis - Menten enzyme kinetics we make assumptions:

Enzyme - Substrate complex is formed (Xray crystallography)

Km is always half of Vmax, measurement of affinity between enzyme and substrate. How good binding is.

Turnover rate is constant for every catalytic reaction

the equilibrium where the rate of ES formation is equal to its breakdown is reached instantaneously.

Equilibrium rate constant is achieved and shown by initial velocity on lineweaver burke plot

There is no k-2 I.e. There is no chance of E + P forming ES – it is an irreversible reaction.

There is reversible reaction of ES => E+S and E+S => ES

[substrate] in ES is negligible; [Enzyme] probably 0.001% of the substrate concentration, so the proportion of substrate locked up in the ES complex is very small.

[enzyme] in ES is neglibible; [Substrate] probably 0.001% of the enzyme concentration, so the proportion of enzyme in the ES complex is very small.

Allosteric Enz; cooperativity

show the simple hyperbolic Michaelis - Menten type kinetic pattern

Initial binding of substrate to one subunit rapidly deccelerates binding to other subunits as substrate concentration increases.

Allosteric regulatory site distinct from the catalytic active site

they produce a sigmoidal pattern on a LINEAR initial velocity vs. Substrate concentration graph.

Allosteric regulatory site equivalent to the catalytic active site

In these enzymes, binding of substrate to one subunit will increase the affinity of other subunits for the substrate

binding of an activator or inhibitor molecule (effector) which is structurally related to the substrate

stimulate or inhibit the enzyme activity by changing the shape of the active site and thus changing its affinity for substrate.

In some cases, the regulatory and catalytic sites are on different types of subunit

e.g Acetylcholinesterase

e.g lysozyme

e.g aspartate transcarbamylase

This enzyme has six catalytic subunits and six regulatory subunits.

This enzyme has three catalytic subunits and regulatory subunits.

Anionic subunit and esteratic subunit

One hydrolyses and another reduces

Called multienzyme

An enzyme with multiple molecular forms (in the same organism) but catalysing the same reaction is known as

Without inhibitor the intercept is -1//Km, with inhibitor it is -1/Km(1+[I]/Ki), so

The ratio (bigger over smaller so it is less than 1) is 1 + [I]/Ki.

The ratio (bigger over smaller so it is greater than 1) is 1 + [I]/Ki.

The ratio (smaller over bigger so it is greater than 1) is 1 + [I]/Ki.

The ratio (smaller over bigger so it is less than 1) is 1 + [I]/Ki.

The ratio (bigger over smaller so it is greater than 1) is 1 - [I]/Ki.

The ratio (bigger over smaller so it is less than 1) is 1 - [I]/Ki.

The ratio (smaller over bigger so it is greater than 1) is 1 - [I]/Ki.

The ratio (smaller over bigger so it is lesser than 1) is 1 - [I]/Ki.

Irreversible enz inhibition

To work in vivo as an enzyme inhibitor

compound is a nonspecific enzyme inhibitor

Enz activity is inhibited for times significantly longer than the assay times for the enz.

Turnover of enz protein in vivo

Turnover of enz protein in vitro

inhibition is reversible in theory but irreversible in practice.

tight-binding inhibitors, transition state analogues and slowly dissociating intermediates.

Timescale of inhibition similar to that of enz action, measured over few mins

A simple reversible inhibitor

Binds noncovalently (ionic interactions, hydrogen bonds, H-bonds) to the enzyme

Competitive inhibitors which are conformationally restricted and/or have many noncovalent interactions leading to long lasting complexes.

Conformationally Restricted Competitive Inhibitor

Higher affinity than substrate to enzyme active site

Strength of binding is of a higher order to the substrate I.e. Ki will be different size to Km.

Binds to Enz and decreases the Enz activity instantaneously and reverses within the time of the enzyme action.

Strength of binding is of a similar order to the substrate I.e. Ki will be of similar size to Km.

Binds to allosteric site on enzyme

A simple reversible inhibitor

Binds noncovalently (ionic interactions, hydrogen bonds, H-bonds) to the enzyme

Competitive inhibitors which are conformationally restricted and/or have many noncovalent interactions leading to long lasting complexes.

Conformationally Restricted Competitive Inhibitor

Higher affinity than substrate to enzyme active site

Strength of binding is of a higher order to the substrate I.e. Ki will be different size to Km.

Binds to Enz and decreases the Enz activity instantaneously and reverses within the time of the enzyme action.

Strength of binding is of a similar order to the substrate I.e. Ki will be of similar size to Km.

Binds to allosteric site on enzyme

Tight binding inhibitors

Conformationally Restricted Competitive Inhibitor

Binds to Enz and decreases the Enz activity instantaneously and reverses within the time of the enzyme action.

Competitive inhibitors which are conformationally restricted and/or have many noncovalent interactions leading to long lasting complexes.

Binds noncovalently (ionic interactions, hydrogen bonds, H-bonds) to the enzyme

Binds to active site on enzyme in competition with substrate

Quasi-irreversible inhibitor

Tight binding inhibitors

Conformationally Restricted Competitive Inhibitor

Binds to Enz and decreases the Enz activity instantaneously and reverses within the time of the enzyme action.

Competitive inhibitors which are conformationally restricted and/or have many noncovalent interactions leading to long lasting complexes.

Binds noncovalently (ionic interactions, hydrogen bonds, H-bonds) to the enzyme

Binds to active site on enzyme in competition with substrate

Quasi-irreversible inhibitor

Analogues of a transition state (or reaction intermediate) for the enzyme catalysed reaction.

Agonist

Drugs bind to receptors, often with high affinity, but do not activate the receptor so they have no intrinsic efficacy.

Rate constants for receptor activation and deactivation, respectively

Measure of the affinity of the drug for the receptor

Stabilise the receptor in the R * state.

Exhibit constitutive activity. In other words, the inactive R complex can convert to the active R * state in the absence of an agonist.

Agonists capable of binding to and stabilising the receptor in both the R and R * states such that although there is full occupancy of the receptor, the efficacy is lower because there are fewer receptors available for conversion to the active state.

A drug that binds to its receptor such that drug-receptor complex is more likely to be in the active R * conformation rather than the inactive R state

always given in molar (moles L−1 ) units and we can use this as a measure of drug POTENCY.

KA (koff / kon)

Stabilise the receptor in the R * state.

A drug that binds to its receptor such that drug-receptor complex is more likely to be in the active R * conformation rather than the inactive R state

maximum response achievable from an applied or dosed agent.

Rate constants for receptor activation and deactivation, respectively

Measure of the affinity of the drug for the receptor

always given in molar (moles L−1 ) units and we can use this as a measure of drug POTENCY.

Efficacy

maximum response achievable from an applied or dosed agent.

Measure of the affinity of the drug for the receptor.

Rate constants for receptor activation and deactivation, respectively

bonds formed are relatively weak (hydrogen bonds or van der Waals, for example). Very few involve covalent bonds which are essentially irreversible.

prevent an agonist from binding to the receptor and activating it.

Positive intrinsic activity

No intrinsic activity

kα and kβ

rate constants for receptor activation and deactivation, respectively.

Dissociation constants for drug receptor complex

Drug affinity function

Drug potency function

Drug efficacy function

Partial agonists

Exhibit constitutive activity. In other words, the inactive R complex can convert to the active R * state in the absence of an agonist.

Drugs bind to receptors, often with high affinity, but do not activate the receptor so they have no intrinsic efficacy.

Will act as an antagonist in the presence of a full agonist because it occupies sites on the receptor thus preventing it from being converted to the R * state.

A drug that binds to its receptor such that drug-receptor complex is more likely to be in the active R * conformation rather than the inactive R state

Inverse agonists

Exhibit constitutive activity. In other words, the inactive R complex can convert to the active R * state in the absence of an agonist.

A drug that binds to its receptor such that drug-receptor complex is more likely to be in the active R * conformation rather than the inactive R state

Agonists capable of binding to & stabilising receptor in both the R and R * states such that although there is full occupancy of receptor, the efficacy is lower because there are fewer receptors available for conversion to active state.

Inverse drug receptor complex from DR active state to DR inactive state

prevent an agonist from binding to the receptor and activating it.

Will act as an antagonist in the presence of a full agonist because it occupies sites on the receptor thus preventing it from being converted to the R * state.

Negative intrinsic activity

Bind to receptors, often with high affinity, but do not activate the receptor so they have no intrinsic efficacy.

Constituitive activity

Can be competitive or noncompetitive

A receptor which is capable of producing a biological-response in the presence of a bound-ligand is said to display

Drugs bind to receptors, often with high affinity, but do not activate the receptor so they have no intrinsic efficacy.

Displayed by receptors in neuromuscular junction

Displayed by inverse agonists

A receptor which is capable of producing a biological-response in the absence of a bound-ligand is said to display

Antagonists

A drug that binds to its receptor such that drug-receptor complex is more likely to be in the active R * conformation rather than the inactive R state

Activity can be competitive or noncompetitive

Inactive R complex can convert to active R * state in the absence of an agonist. Drugs that bind to the R complex now have the effect of reducing the response mediated by constitutively active receptors.

Drugs bind to receptors, often with high affinity, but do not activate the receptor so they have no intrinsic efficacy.

prevent an agonist from binding to the receptor and activating it.

Competitive antagonist

Competitive antagonism

Binds to rec site distinct from agonist or to element in cascade of events leading to biological respones. Not reversible/effect overcome by ^[agonist]

Competitively binds to active site of agonist and overcome by ^[agonist]

Non competitive antagonist

Competitive antagonism

Binds to rec site distinct from agonist or to element in cascade of events leading to biological respones. Not reversible/effect overcome by ^[agonist]

Competitively binds to active site of agonist and overcome by ^[agonist]

May appear irreversible as dissociation may occur slowly

Competitive antagonism

Binds to rec site distinct from agonist or to element in cascade of events leading to biological respones. Not reversible/effect overcome by ^[agonist]

Competitively binds to active site of agonist and overcome by ^[agonist]

Competitive antagonism

Binds to rec site distinct from agonist or to element in cascade of events leading to biological respones. Not reversible/effect overcome by ^[agonist]

Competitively binds to active site of agonist and overcome by ^[agonist]

Explain the basic principles of drug-receptor binding and be familiar with the terms efficacy and potency.

Define the terms full agonist, partial agonist, competitive and non-competitive antagonist and be able to represent their effects graphically.

Define the term pA2 and explain, in general terms, how this value can be derived for a competitive antagonist.

Describe, in general terms, allosteric modulation at a named receptor.

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