IMMS (summary Sheets) Flashcards
What is the structure of DNA?
- Double helix
- Complimentary base pairs (A - T & G - C)
- Coils around nucleosomes —> supercoils —> chromosomes
What is a autosome?
Any chromosome which isn’t sex determining
How many pairs of chromosomes are there in humans?
22 pairs of autosomes & a pair of sex chromosomes
What are the sex chromosomes in males and females?
XY - males
XX - female
Define karyotype
Number and appearance of chromosomes in a cell
What does each chromosome contain?
A continuous DNA duplex of 10^7 base pairs and contains several hundred genes
How many genes does each individual have?
30,000
What is the structure of a chromosome?
Has a long arm (q) and a short arm (p) separated by a centromere
What is the purpose of mitosis?
To produce 2 daughter cells, genetically identical to parent cells
What is mitosis used for?
Growth and to replace dead cells
What is the DNA structure called when not in replication?
Chromatin
What is the DNA structure called when in replication?
Chromosomes
What is the DNA structure called when after replication?
Chromatids
What must happen for mitosis to occur?
The cell must be in cell cycle - interphase
What is the longest phase of mitosis?
Interphase
What happens in G1 of interphase?
- No visible activity
- Rapid growth
- Normal metabolic function
- New organelles produced
- Protein synthesis of proteins involved in spindle formation
What happens in S (synthesis) of interphase?
- DNA doubles through DNA replication
- Histone proteins double through protein synthesis (2x as much DNA at end of S)
- Centrosome replication
What happens in G2 of interphase?
- Chromosomes condense (coil up and become visible)
- Energy stores accumulate
- Mitochondria and centrioles double
What happens in prophase in mitosis?
- Chromatin condenses into chromosomes
- Centrosomes nucleate microtubules and move to opposite poles of nucleus
What happens in prometaphase in mitosis?
- Nuclear membrane breaks down
- Microtubules invade nuclear space
- Chromatids attach to microtubules
- Cell no longer has a nucleus
What happens in metaphase in mitosis?
- Chromosomes line up along equatorial plane (metaphase plate)
What happens in anaphase in mitosis?
- Sister chromatids separate, and are push to opposite poles of the cells, centromere first, as spindle fibres contract
What happens in telophase in mitosis?
- Nucelar membrane reforms
- Chromosomes unfold into chromatin
- Cytokinesis begins
What happens in cytokinesis in mitosis?
- Cell organelle become evenly distributed around each nucleus
- Cell divides into two daughter cells with a nucleus in each and 46 chromosomes
Histologically, how can you tell if a cell is undergoing mitosis?
If the nucleus is dark and the nuclei are not the same size
When is something defined as malignant?
If there are too many mitotic figures e.g. lots of dark nuclei of different sizes
What are mitotic figures used for?
Determine how bad cancer is - more there are, the worse it is
What differentiates meiosis from mitosis?
Meiosis:
- Only in gametes
- Recombination of genetic material results in genetic diversity
- Two cell divisions
- 4 haploid (HALF number of chromosomes - 23) cells produced, which are genetically distinct from each other and the parent cell
- Not a cycle
What happens in meiosis I?
- Chromosome number is halved
- In prophase I, crossing over occurs between non-sister chromatids (genes sort independently thus if 1 gene switches over, doesn’t mean another one will), resulting in genetic diversity
- In metaphase I, random assortment occurs on the metaphase plate - also resulting in genetic diversity
What happens in meiosis II?
- Sister chromatids separate
- Haploid cells produced
What is the first stage of gametogenesis?
The proliferation of primordial (undifferentiated) germ cells (developing gametes) by mitosis
What is the process of gametogenesis in males?
- Primordial germ cells to lots of mitoses to spermatogonia (mature sperm)
- Some mitosis occurs in embryonic stages to produce primary spermatocytes present at birth
What is the process of gametogenesis in males at puberty?
- Mitosis really begins during puberty and continues throughout life
- Cytoplasm divides evenly
- After meiosis 2 - four equal size gametes
- Millions of mature sperm continually produced
How long does the production of mature sperm take?
60-65 days
How many sperm are there per ejaculate?
100-200 million
What is the process of gametogenesis in females?
- Primordial germ cell to 30 mitoses to oogonia
- Oogonia enter prophase I of meiosis 1 by 8th month of in-utero life
- Process then suspended
What is the process of gametogenesis in females at puberty?
- Cells enter ovulation
- Cytoplasm divides unequally (1 egg and 3 polar bodies - PB apoptose)
- Meiosis I is completed at ovulation (there is 1 big cells 1 small cell each with diploid DNA)
- Then goes on to divide again each (after fertilisation) to form 1 big cell (egg) and 3 small cells (polar bodies)
- Meiosis 2 is only completed if fertilisation occurs
What is non-disjunction?
Failure of chromosome pairs to separate in meiosis I or sister chromatids to separate properly in meiosis II
When does gonadal mosaicism occur?
When precursor germline cells to ova or spermatozoa are a mixture of two or more genetically different cell lines
Gonadal mosaicism mainly causes which genetic problems?
Autosomal dominant or X-linked
What are the 3 causes of diseases?
Genetic, multifactorial and environmental
Give 4 examples of genetic diseases
- Down’s syndrome
- Cystic fibrosis
- Huntington disease
- Haemophilia
Give 4 examples of multifactorial diseases
- Spina bifida
- Cleft lip/palate
- Diabetes
- Schizophrenia
Give 4 examples of environemental diseases
- Poor diet
- Infection
- Drugs
- Accidents
Define autosomal
Chromosomes 1-22, all chromosomes except the sex chromosomes (X/Y)
Define locus
The position of a gene/DNA on the genetic map
Define genotype
Genetic constitution of an individual
Define phenotype
Appearance of an individual which results from the interaction of the environment and the genotype
Define allele
One of several alternative forms of a gene at a specific locus
- Normal allele is also referred to as wild type
- Disease allele carries the pathogenic mutation
Define polymorphism
Frequent hereditary variations at a locus. Doesn’t cause problems. They make you more/less efficient or more/less susceptible to disease
Define consanguinity
Reproductive union between two relatives
Define autozygosity
Homozygous by descent e.g. inheritance of the same mutant allele through two branches of the same family
Define homozygous
Both alleles are the same at a locus
Define heterozygous
Alleles at a locus are different
Define hemizygous
Describes genes that are carried on an unpaired chromosomes. Refers to a locus on an X chromosomes in a male
Define penetrance
Proportion of people with a gene/genotype who show the expected phenotype
Define complete penetrance
Gene or genes for the trait are expressed in all the population
Define incomplete penetrance
The genetic trait is only expressed in parts of the population
Define variable expression
Variation in clinical features (type and severity) of a genetic disorder between individuals with the same gene alteration
Define sex limitation
Expression of a particular characteristic limited to one of the sexes
Define multifactorial condition
Diseases due to a combination of genetic and environmental factors. In relation to family: if a male has condition, then female relatives are more at risk and vice versa (if condition is more prevalent in one sex)
Define late-onset
Condition not manifested at birth
Define congenital onset
Condition manifested at birth
Define autosomal dominant (Mendelian)
- A disease that only manifests in the heterozygous state
- Affects both males and females in equal proportions
- Affected individuals in multiple generations
- Transmission by individuals of both sexes to both sexes
- Only way to pass disease male to male
Define autosomal recessive (Mendelian)
- A disease that manifests in the homozygous state
- Two defective genes required
- Healthy siblings have a 2/3 chance of being carriers
- Male and females affected in equal proportions
Define X-linked (sex-linked) inheritance (Mendelian)
Caused by a mutation in genes on the X-chromosome
Why are X-linked conditions never passed from father to son?
Due to sons getting their X-chromosome from their mother
What are the outcomes to offspring of males with an X-linked condition?
- All daughters are carriers
- All sons are unaffected
- Males can never be carriers
Define lyonisation
The process of X chromosome inactivation
What happens to one of the two X chromosomes in every cell in a female and why?
- It is randomly inactivated early in embryonic development
- To prevent female cells having twice as many gene products compared to males
What happens to the inactive X chromosome in females?
Packaged in heterochromatin (can’t be transcprited)
What causes sporadic cancers?
2 acquired mutations
What causes hereditary cancers?
1 inherited mutation and 1 acquired mutation
What is an ideogram?
Diagrammatic form of chromosome bands, bands are numbered according to distance to centromere
What are the classifications of genetic disease?
- Chromosomal
- Mendelian (autosomal dominant/recessive or X linked)
- Non-traditional e.g. mitochondrial, imprinting, mosaicism
What does a square mean in a genetic pedigree?
Male
What does a circle mean in a genetic pedigree?
Female
What does a coloured-in object mean in a genetic pedigree?
Affected
What is epithelia?
One or more layers of cells that line a body cavity
What are the 3 functions of epithelia?
Protection, absorption or secretion
Name 4 supporting tissues of the body
- Cartilage
- Bones
- Tendons
- Blood
What is the function of supporting tissues?
Structure and protection
What are the three types of muscle?
Smooth, skeletal and heart
What are the 3 broad types of nerves?
Brain, peripheral and visceral
What are the two germ cells?
Ova and sperm
What does haemtoxylin stain and what colour?
Acid things - blue
What colour does eosin stain and what colour?
Alkaline things - pink
What colour does haemotoxylin stain cell nuclei and RNA?
Blue
What colour does eosin stain cytoplasm and colloidal proteins?
Pink
What colour does eosin stain keratin?
Orange/red
What colour does eosin stain extracellular fibres (e.g. collagen and elastic)?
Pink
What doesn’t stain with H&E?
Extra-cellular jelly & fat
What colour does alcian blue stain GAG rich structures?
Blue
Where are GAG rich structures found?
In all connective tissue and extracellular matrix
What colour does alcian blue stain mucous goblet cells?
Blue
What colour does alcian blue stain mast cell granules?
Blue
What colour does alcian blue stain the cartilage matrix?
Blue
What colour does iron haemotoxylin stain nuclei and elastic fibres?
Black
What colour does PAS stain hexose sugars?
Magenta
What colour does toluidine blue stain nuclei, ribosomes and cytoplasm?
Dark blue
What colour does toluidine blue stain the cartilage matrix and mast cell granules?
Pale blue
What colour does toluidine blue stain GAG-rich components?
Bright purple
What is the structure of the nucleus of the cell?
- Brain of the cell
- Double nuclear membrane
Where in the cell houses DNA?
The nucleus - in the form of chromatin within the nucleus
What is the site of rRNA formation?
The nucleolus
What is the site of oxidative phosphorylation?
Mitochondria
What is the structure of the mitochondria?
- Double membrane
- Inner membrane is highly folded
What happens in the outer membrane of the mitochondria?
- Lipid synthesis
- Fatty acid metabolism
What happens in the inner membrane of the mitochondria?
Respiratory chain (electron transport) ATP production
What happens in the matrix of the mitochondria?
TCA (Krebs’) cycle
What happens in the intramembranous space of the mitochondria?
Nucelotide phosphorylation (ADP to ATP)
What makes RER rough?
Due to numerous ribosomes on the surface
What is the site of protein synthesis?
RER
What is the structure of the RER?
Highly folded flattened membrane sheets
What is the site of membrane lipid synthesis?
SER
Where in the cell processes and stores synthesised proteins?
The SER
What is the structure of the SER?
Highly folded flattened membrane sheets
What is the structure and general function of the Golgi apparatus?
- Parallel stacks of membrane
- Processes and modifies macromolecules synthesised in the ER
What is the function of the cis Golgi?
- Receives SER vesicles
- Protein phosphorylation occurs here
What is the function of the medial Golgi?
- Modifies products by adding sugars
- Forms complex oligosaccharides by adding sugars to lipids and proteins
What is the function of the trans Golgi network?
- Proteolysis of peptides into active forms
- Sorting molecules into vesicles which bud from the surface
In which cells can the Golgi apparatus be clearly seen?
Plasma cells
What are vesicles?
Very small, spherical membrane-bound organelles which transport & store material and exchange cell membrane between compartments
Name 4 types of vesicles
- Cell-surface derived (pinocytotic & phagocytotic)
- Golgi-dervied
- ER-derived
- Lysosomes & peroxisomes
How does the waste-dsiposal system of the lysosomes work?
- H ions are pumped onto membrane
- Creates a low pH to enable acid hydrolases to function
- Break down debris from dead cells
What are the functions of peroxisomes?
- Involved in the process which fatty acids are broken down
- Used to destroy hydrogen peroxide which is a product of FA breakdown.
What is the cytoskeleton and what is its function?
- Filamentous proteins which brace the internal structure of the cell
- Helps cells maintain their shape and internal organisation
Are cytoskeletons visible in light microscopy?
No
Name the 3 filaments of the cytoskeleton in increasing size
- Microfilaments (5nm)
- Intermediate filaments (10nm)
- Microtubules (25nm)
Name a microfilament?
Actin
How does actin work as a microfilament?
Forms a bracing mesh on the inner surface of the cell membrane
How do intermediate filaments work?
Anchored transmembrane proteins which can spread tensile force through tissues
Where can cytokeratins be found?
Epithelial cells
Where can desmin be found
Myocytes
Where can glial fibrillary acidic protein be found and what is its function?
- Astrocytic glial cells
- Supports neurones in the brain
Where can neurofilament protein be found?
Neurones
Where can nuclear laminin be found?
Nuclei of all cells
Where can vimentin be found?
Mesodermal cells
Name a type of microtubule
Tubulin
Where do microtubules originate from?
A centrosome
In what cells can microtubules be found in?
All cells except from erythrocytes
What is lipofuscin?
- Membrane-Bound orange-brown pigment
- Peroxidation of of lipids in older cells
Where is lipofuscin common?
In the heart and liver (sign of wear and tear)
How does lipid appear as a storage product?
- Non-membrane bound vacuoles
Where is lipid stored in the body?
In adipocytes and liver
How does lipid appear histologically?
As empty space
What is the structure of glycogen as a storage product?
CHO polymer in cytoplasm
Which elements are the molecular building blocks?
Carbon, hydrogen, oxygen, nitrogen, sulphur and phosphate
What are macromolecules and what are their functions?
- Simple molecules such as sugars, lipids and amino acids which can form complex large molecules
- Have osmotic, structural, optical, enzymatic and other complex functions
Give 5 examples of macromolecules
- Haemoglobin
- DNA
- Glycogen
- Rhodopsin
- Collagen
What is the general formula of carbohydrates?
Cn(H2O)n
Give 4 examples of general carbohydrates?
- Monosaccharides
- Disaccharides
- Oligosaccharides
- Polysaccharides
What is maltose compromised of?
2 x glucose
What is sucrose comprised of?
Glucose & fructose
What is lactose compromised of?
Glucose & galactose
What is the general structure of a monosaccharide?
Chain of carbons, hydroxyl groups and one carbonyl (C=O) group
What is an aldose?
A monosaccharide with an aldehyde group
What is an ketose?
A monosaccharide with a ketone group
What is a chiral centre?
A carbon with 4 different chemical groups
What is the difference in D&L monosaccharides?
Have the same chemical properties but different biological ones
Are most sugars in living organisms in the D or L form?
D
What is a glycosidic bond?
When he hydroxyl group of a monosaccharide can react with an OH or an NH group of another monosaccharide
Where are O-glycosidic bonds found?
In disaccharides, oligosaccharides and polysaccharides
Where are N-glycosidic bonds found?
In nucleotides and DNA
What is an oligosaccharide?
Disaccharide joined by a O-glycosidic bond
What is a proteoglycan?
Long, unbranched polysaccharides radiating from a core protein
What is the structure of starch?
- Storage in plants
- Made of amylose (glucose alpha 1,4) and amylopectin (glucose alpha 1,4 & alpha 1,6 glycosidic bonds)
What is the structure of glycogen?
- Storage in animals
- Branched polysaccharide formed of glucose residues
- Linking is both alpha 1,4 & alpha 1,6
What is a triglyceride compromised of?
3 fatty acids bound to glycerol
What happens to the melting point of a lipid with increased fluidity?
Decreases
What are the building blocks of DNA?
Nucleotides
What are nucleotides compromised of?
A nitrogenous base, pentose sugar and a phosphate group
What are the bonds between bases in-between nucleotides?
Hydrogen bonds
What are the bonds between phosphate and sugar in nucleotides?
Phosphodiester bonds
What is the source of energy in nucleotides?
The phosphate bonds
What are the building blocks of proteins?
Amino acids
How many amino acids are there?
20
What are the structures of amino acids?
Carbon with amino group, carboxyl group and side chain
How is the charge of an amino acid determined?
By all three components. Charge changes somewhat with the pH of the solution
How is the polarity of the amino acid determined?
By the side chain
Are the carboxyl groups of amino acids positive or negative?
Negative
Are the amino groups of amino acids positive or negative?
Positive
Are amino acids naturally in the D or L form?
L
How are peptide bonds formed?
By condensation reaction (water released) between carboxyl group and amino group
How are proteins formed?
By linked amino acids which are bonded together by peptide bonds
What is the folding of a protein determined by?
- Charged interactions
- Flexibility
- Physical dimensions
How is the identity of the protein determined?
By the sequence of amino acids, folding and structure
Are peptide bonds stable?
Yes - very
How are peptide bonds cleaved?
Proteolytic enzymes - proteases or peptidases
What is a protein?
A large polypeptide, usually form 10s to 1000s of amino acids
What is the function of a protein dependent on?
Structure
What is the primary structure of a protein?
A linear sequence of amino acids, held together by covalent bonds
What is the secondary structure of a protein?
Formation of either alpha helix or beta pleated sheets due to hydrogen bonds between amino acids - determined by the local interactions between the side chains and sequence of amino acids
What is a super-secondary structure of a protein?
Combination of secondary structures
What is the tertiary structure of a protein?
- Overall 3D conformation of a protein
- Bonding involved is electrostatic, H-bonds and covalent bonds
- This occurs due to ionic bonds, disulphide bridges or Van Der Waals forces
What is the quaternary structure of a protein?
- 3D structure of protein composed of multiple subunits
- Same non-covalent interactions as tertiary structures
- 2 or more tertiary structure joined together to form a protein
What are the 5 forces which hold proteins together?
- Van der Waals forces
- Hydrogen bonds
- Hydrophobic forces
- Ionic bonds
- Disulphide bonds
What is a Van der Waals force?
Weak attractive/repulsive force between all atoms due to fluctuating electrical charge
What is a hydrogen bond?
Interaction between polar groups
What is a hydrophobic force?
As uncharged and non-polar side chain are repelled by water, these hydrophobic side chains tend to form tightly packed cores in the interior of proteins, excluding water molecules.
What is an ionic bond?
- Between fully/partially charged groups
- Weakened in aq systems by water molecules and other ions in solution
What are disulphide bonds?
Very strong covalent bonds between sulphur atoms
Name 6 factors which influence the rate of reaction
- Temperature
- pH
- Conc of reactants
- Catalyst
- SA of solid reactant
- Pressure of gaseous reactants/products
How can enzymes be used for diagnostic purposes?
As they control metabolism they can be used for disease markers
What is the primitive function of enzymes?
Provide an alternative reaction pathway with a lower activation energy
How do enzymes work?
Bind the substrates and convert them to products, they then release the products and return to their original form
How can enzymes be regulated?
By altering the concentration of substrates, products, inhibitors or activators
What is a isoenzyme?
Enzymes which have a different structure and sequence but catalyse the same reaction
What is a coenzyme?
They can’t catalyse a reaction themselves, but can help enzymes to do so. They can bind with the enzyme protein molecule to form the active enzyme
What are activation-transfer coenzymes?
Form a covalent bond and are regenerated at the end of the reaction
What are oxidation-reduction coenzymes?
Involved in reactions where electrons are transferred from one compound to the other
What is haemoglobin and where is it found?
- Found in red blood cells
- Oxygen carrier in blood
What is myoglobin and where is it found?
- Serves as a reserve supply of oxygen
- Facilitates the movement of oxygen in muscles
- Found in muscles
Are myoglobin and haemoglobin the same?
They have the same tertiary structure but not quaternary
What is at the core of both haemoglobin and myoglobin?
The porphyrin ring which holds an iron atom
Name 3 broad factors which influence haemoglobin saturation?
- Partial pressure of O2 in blood, as it increases so does haemoglobin saturation
- Temperature, H+ and partial pressure of CO2
- Sickle cell anaemia
How do temperature, H+ and partial pressure of CO2 influence haemoglobin saturation?
All modify the structure of haemoglobin and alter its affinity for O2
What is another name for immunoglobulins?
Antibodies
What is the main function of immunoglobulins?
To bind to antigens
What are antibodies produced for?
To bind to antigens on toxins or proteins
Is antibody-antigen binding specific?
Yes - one antibody only matches one antigen
How are antigens bound to the antibody?
- By the variable domain
- Amino acid in the variable domain can be varied to produce an infinite variety of foreign antigens
Where is DNA found?
- The nucleus
- The mitochondria (purely maternal DNA)
What is the structure of DNA in prokaryotes?
No nuclear membrane, DNA arranged often in single chromosome
What is the structure of DNA in eukaryotes?
- DNA is in the nucleus, bound to proteins (chromatin complex)
What are the functions of DNA?
- A template and regulator for transcription and protein synthesis
- DNA is the genetic material thus the structural basis of hereditary and genetic diseases
What is the structure of nucleic acids
- The building blocks to make new DNA
- Free phosphate groups provide energy for the reaction to go through
How does DNA polymerase read the template strand?
From 3’ to 5’ thus DNA is synthesised on the daughter strand from 5’ to 3’ as DNA runs antiparallel
What is phosphate at 5’ of DNA used for?
A source of energy for the reaction of DNA synthesis to occur
Why is DNA replication semi-conservative?
Because each resulting DNA double helix retains one strand of the original DNA
What are the enzymes and proteins involved in DNA replication?
- Topoisomerase
- DNA helicase
- DNA polymerase
- Primer
- Single strand binding protein
- Primase enzyme
- RNAse H
What is the function of topoisomerase?
Unwinds the double helix by relieving the supercoils
What is the function of DNA helicase?
Separates the DNA apart, by breaking hydrogen bonds between bases, exposing nucleotides
What is the function of DNA polymerase?
Reads 3’ to 5’ and synthesises DNA on daughter strand 5’ to 3’ - creates DNA by working in pairs to make 2 new strands of DNA. Starts at primer.
What is the function of a primer?
A short strand of DNA that is the start point for DNA synthesis as DNA polymerases can only add nucleotides on to an existing strand of DNA
What is a single strand binding protein?
Keeps two strands of DNA apart whilst synthesis of new DNA occurs - prevents annealing to form double stranded DNA
What is the function of primase?
RNA polymerase that synthesises the short RNA primers needed to start the strand replication process
What is the function of RNAse H?
Removes the RNA primers that previously began the DNA strand synthesis