IMMS Flashcards
What is the protein in tight junctions?
Occludins
What is the type of protein in adhering junctions?
(E-) Cadherins
What is the transmembrane protein in desmosomes?
Cadherin - e.g. Desmogeins & desmocollins
What is the intermediate filament in epithelial desmosomes?
Keratin
What is the intermediate filament in desmosomes in cardiac cells?
Desmin
What is the transmembrane protein in hemidesmosomes?
Integrin
What is the name of the channel between gap junctions?
Connexon - formed from connexins
What is gametogenesis?
Formation of mature haploid gametes.
This is either through meitotic division of diploid cells or mitotic division of haploid cells
What is Mendel’s second law?
Law of Independent assortment:
Biological selection of an allele has no affect on the selection of another allele
What is the definition of homeostasis?
The state of equilibrium (balance between opposing pressures) in the body with respect to various functions and to chemical compositions of the fluids and tissues.
Essentially, the mechanism in which the body maintains a regulated and stable internal environment
What is the total water content of the body in litres for an average 70kg man?
42L
What is the average water content in litres of the intracellular fluid?
28L
What is the average water content of extra cellular fluid in litres?
14L
What are the two types of extra cellular fluid?
1) interstitial fluid
2) blood plasma
What is the definition of penetrance?
The proportion of people with a gene/genotype which show the expected phenotype.
Can be:
Complete - expresses by all in that genetic population
Incomplete - expressed by only parts of that population
What is an allele?
One of several alternative forms of a gene at a specific locus
What is variable expression?
Variation in clinical features (type & severity) of a genetic disorder between individuals with the same gene alteration
What is sex limitation?
Where the expression of a particular characteristic is limited to one of the sexes
What is meant by genotype?
The genetic constitution of an individual
What is meant by phenotype?
The appearance of an individual which is down to a combination of environmental & genetic factors
What is an autosomal dominant genetic disorder?
A disease that can manifest in a heterozygous state - only one allele needed as it is dominant.
If one parent has an autosomal dominant condition what are the chances the offspring have the condition?
50%
What is a common example of an autosomal dominant condition?
Huntigtons
What is meant by an autosomal recessive disease?
A disease that can only manifest in a homozygous state - two of the alleles are needed
What percentage of offspring would have the recessive condition if the parents were both carriers?
25%
What percentage of offspring would be carriers of the recessive allele if both parents were carriers?
50%
What is meant by X-linked (sex-linked) genetic diseases?
Diseases that are a result of a mutation of the X chromosome
Can there be male to make transmission of X-linked genetic diseases? Why?
No. This is because if a man has a son he will have passed a Y chromosome onto the son, not an X chromosome.
Can males be carriers of X-linked genetic diseases?
No. It would manifest as they only have one X chromosome, there’s no other chromosome to counteract.
What percentage of daughters would be affected if the father had an X-linked genetic disease?
100% would be affected in some way.
If recessive - they would be carriers
If dominant - they would have the condition
What is meant by the term lyonization?
It is where one of the X-chromosome in a female are inactivated. The inactive form is known as a Barr body
What is Kudson’s 2-hit hypothesis?
The idea about genetic mutations being inherited or acquired.
Sporadic cancer - 2 acquired mutations
Hereditary cancer - 1 inherited & 1 acquired
What enzyme converts glucose to glucose-6-phosphate?
Hexokinase
What stages of glycolysis use ATP?
1 and 3
What stages of glycolysis release ATP?
1,3-biphosphoglycerate to 3-phosphglycerate
And
Phosphoenolpyruvate to pyruvate
What is the overall yield of glycolysis
2 ATP, 2 NADH and 2 pyruvate molecules
Where does glycolysis occur?
In the cytosol of the cell
Glycolysis requires oxygen. True or false?
False - it is an oxygen independent process
How many enzyme catalysed reactions are their in glycolysis?
10
What are the molecules in the Krebs cycle starting with pyruvate?
Pyruvate > acetyl CoA > Citrate > Isocitrate > alpha-ketoglutarate > Succinyl CoA > Succinate > Fumarate > L-Malate > Oxaloacetate
What enzyme converts Citrate to Isocitrate?
Aconitase
What enzyme converts Isocitrate to alpha-ketoglutarate?
Isocitrate dehydrogenase
What enzyme converts alpha-ketoglutarate to Succinyl CoA?
Alpha-ketoglutarate dehydrogenase
What enzyme converts Succinyl CoA to Succinate?
Succinyl CoA synthase
What enzyme converts Succinate to Fumarate?
Succinic dehydrogenase
What enzyme converts Fumarate to L-Malate?
Fumarase
What enzyme converts L-malate to Oxaloacetate?
Malate dehydrogenase
What is the yield of the Krebs cycle in one round?
1 ATP’s, 3 NADH’s and 1 FADH2 per glucose molecule
What is the maximum potential ATP yield from aerobic respiration?
38
Where does the Krebs cycle occur?
In the matrix of the mitochondria
Where does oxidative phosphorylation occur?
Across the inner membrane of the mitochondria
How many protein complexes are there in the electron transport chain?
5
What is the energy released from the electrons used to do as they pass along the electron transport chain?
Pump hydrogen ions into the inter-membrane space
What is chemiosmosis?
Where the hydrogen ions that have been pumped into the inter membrane space pass down their concentration gradient through ATP synthase (ATPase). This movement is used to generate the ATP
When does ketogenesis occur?
Where there is an unavailability of blood glucose. E.g. During fasting
What can happen if ketogenesis is insufficient?
Hypoglycaemia
What can happen if ketogenesis is excessive?
Ketoacidosis
What is beta oxidation of fatty acids?
The process of which fatty acids are broken to form acetyl CoA
Where does beta oxidation of fatty acids occur?
In the mitochondria
What is the process of beta oxidation of fatty acids?
1) Fatty acids are activated and transported across the membrane by binding to coenzyme A
2) Oxidation of the beta carbon to a carbonyl group occurs
3) Cleavage of two carbon segments results in the production of acetyl-CoA
4) Acetyl-CoA feeds into the Krebs cycle
5) Cycle repeats until full fatty acid breakdown
What is a buffer?
A compound that resists a change in pH, by preventing an increase or decrease in hydrogen ion concentration, when a small amount of acid or alkali is added
What are the main sources of hydrogen ions?
1) Oxidation of amino acids
2) anaerobic respiration
3) Aerobic respiration through formation of CO2
What does ROS stand for?
Reactive Oxygen Species
What is a reactive oxygen species?
A chemically reactive molecule containing oxygen
What are the two types of Reactive oxygen species?
1) Endogenous - Generated in the body e.g. In oxidative phosphorylation
2) Exogenous - Produced from external sources e.g. Pollutants, tobacco, smoke, drugs, xenobiotics or radiation
What is an endogenous source of superoxide (.O2)
Oxidative phosphorylation (0.1-2% of electrons that pass down the electron transport chain and incompletely reducing oxygen to superoxide)
Note: oxygen is supposed to be reduced to water
What is a respiratory burst?
The rapid release of reactive oxygen species (superoxide and hydrogen peroxide) from cells.
Forms hydroxyl radical and HOCl
What role do respiratory bursts play?
They are important in the immune response. They are important in phagocytosis to degrade internalised particles and bacteria.
E.g. Immune cells use NADPH oxidase to reduce O2 to an oxygen free radical and then to hydrogen peroxide. This is combined with chloride (hypochlorite) and this is used to destroy bacteria.
What is the rate determining step in glycolysis?
Step 3 - phosphofructokinase reaction
What is the normal pH of the blood?
pH 7.4 (7.35-7.45)
What cells have a lifespan of a persons entire life?
Nerves, cardiac muscle, germ cells
What cells have a lifespan of nearly a whole life, they have limited regeneration?
Skeletal muscle
What cells survive for years but are regenrated?
Bones and tendons
What cells have a turnover of a few months?
Blood, skin, connective tissues
What cells have a turn over of days or less?
White blood cells
Cells lining the gut
Euchromatin is found in the nucleus, what is it?
Lightly packed chromatin that is usually under active transcription
Heterochromatin is found in the nucleus, what is it?
Densely packed chromatin that is not under active transcription
What is a nucleolus
It is a ribosome “factor” found in the nucleus of a cell
What is chromatin?
It is a complex of DNA and proteins that forms chromosomes within the nucleus of the cell
What are two characteristics of mitochondria?
1) Have their own DNA
2) Have a double membrane - the inner is highly folded
What is the main function of mitochondria?
The site of oxidative phosphoryation
What is the function that occurs in the outer membrane of mitochondria?
Lipid synthesis and fatty acid metabolism
What is the function that occurs in the inner membrane of the mitochondria?
Respiratory chain and ATP production
What is the function that occurs in the matrix of the mitochondria?
The krebs cycle
What is the function that occurs in the intermembraneous space of mitochondria?
Nucleotide phosphorylation (ADP to ATP)
What is the function of Rough Endoplasmic Reticulum
Site of protein synthesis
What is the function of smooth endoplasmic reticulum?
Lipid synthesis and processing of synthesised proteins
What is the function of Golgi apparatus?
Processes macromolecules synthesised in the ER
How does the Golgi apparatus modify macromolecules?
1) Adds sugars
2) Proteolysis of peptides into active forms
3) Sorts macromolecules
What function occurs at the cis face of the Golgi apparatus?
Recieves transport vesicles from smooth ER and phosphorylates some proteins
What function occurs at the medial part of the Golgi body?
Forms complex oligosaccharides by adding sugars to lipids and peptides
What function occurs in the Trans Golgi network?
Proteolysis and the sorting of the macromolecules into vesicles which bud from the surface
What are the types of vesicles?
1) Cell-surface derived: Pinocytotic and phagocytotic
2) Golgi-derived transport vesicles
3) ER-derived transport vesicles
4) Lysosomes
5) Peroxisomes
What are lysosomes?
Derived from Golgi apparatus
H+ - ATPase on memebrane creates low pH (pH5)
Contains acid hydrolase
What are peroxisomes?
Small membrane-bound organells containing enzymes that oxidise long-chain fatty acids
What are endolysosomes?
They result when hydrolase vesicles fuse with endosomes with the correct membrane proteins
What are the enzymes in peroxisomes?
D-amino acid oxidase
Catalase
Ureate oxidase
What is the cytoskeleton?
Filamentous proteins which brace the internal structure of the cell
What three types of filamentous proteins compose the cytoskeleton?
1) Microfilaments
2) Intermediate filaments
3) Microtubules
What type of filamentous protein is actin?
Microfilament
What proteins are microtubules made up of?
Alpha and beta tubulin
Microtubules are found in all cells except what?
Erythrocytes
Where do the microtubules arise from? what is this structure composed of?
Arise from centrosome which is comprised of 2 centrioles
What is the general function of intermediate filaments?
They are anchored to transmembrane proteins and thus spread tensile forces through tissues
What type of intermediate filament is found in epithelial cells?
Cytokeratins
What type of intermediate filament is found in neurons?
Neurofilament protein
What is lipofuscin?
They are membrane-bound with an orange-brown pigment.
They are involved in the peroxidation of lipids and are common in the heart and liver
What is an oligosaccharide?
A carbohydrate polymer comprised of three to twelve monosaccharides
What is a polysaccharide?
A carbohydrate polymer comprised of a long chain of monosaccharides
Monosaccharides can exist in two optically different forms, why?
They have a chiral center - a carbon with four different chemical groups around it
Molecules can exist in both L and D arrangements, which are the majority in living organisms?
D
How does a glycosidic bond form?
When a hydroxyl group reacts with an OH or an NH to form glycosides
Where are O-glycosidic bonds found?
Diasaccharides, oligosaccharides and polysaccharides
Where are N-glycosidic bonds found?
In nucleotides and DNA
What is starch composed of?
Glucose in two forms.
Amylose (Alpha 1,4 glycosidic bonds)
Amyopectin (Alpha 1,6 glycosidic bonds)
What are proteoglycans?
Long, unbranched polysaccharides that radiate from a core protein
What is glycogen?
A storage form of glucose.
A polysaccharide of glucose with alpha 1,4 and alpha 1,6 glycosidic bonds
What is a fatty acid?
A chain of carbon atoms with a methyl group at one end and a carboxyl group at the other
What are Eicosanoids?
Synthesised from 20 C atom acids with 3,4,5 double bonds
What are nucleotides composed of?
Nitrogenous base, sugar and phosphate
Whta is the name for the part of the nucleotide not containing the phophate
Nucleoside
Whta type of bond holds amino acids together in a chain?
Peptide bond
What is a peptide bond?
(C=O)N(H)
What forces hold proteins together?
Van der Waals Hydrogen bonds Hydrophobic forces Ionic bonds Disulphide bridges
What are Van der Waals forces?
Weak attractive interactions between atoms due to fluctuating electrical charges
What are hydrogen bonds?
The strongest type of Van der Waals force.
Where a Hydrogen atom is bonded to an oxygen/fluorine/nitrogen
Hydrogen becomes partially positively charged, other atom partially negative
What are hydrophobic forces?
Where uncharged and non-polar side chains are poorly soluble in water and effectively repel water
What are ionic bonds?
Occur between fully or partially charged groups. these are weakened in solution as shielded by water molecules
what are disulphide bridge bonds?
Convalent bonding between two sulphur atoms in the side chains of cysteine residues
What are isoenzymes?
Enzymes that have a different structure and sequence but catalyse the same reaction
What are coenzymes?
Complex organic structures that help maximize the repertoire of enzymes functional groups - can be metal ions or organic (derived from vitamins)
What are activation-transfer coenzymes?
Coenzymes that form covalent bonds and a re regenerated at the end of the reaction
What are oxidation-reduction coenzymes?
Coenzymes that are involved in reactions that involve the transfer of electrons from one compound to another
What is the heme part of haemoglobin formed from?
Porphyrin ring that contains iron
Describe the process in which CO2 is taken into a RBC and O2 is released
1) CO2 combines with H2O to form carbonic acid
2) Carbonic acid dissociates to HCO3- and H+
3) H+ binds to Hb
4) Hb releases O2
Describe the process in which O2 is taken into RBC and CO2 is released
1) O2 binds to protonated Hb
2) Hb releases H+
3) H+ binds to HCO3- to form carbonic acid
4) Carbonic acid is cleaved to H2O and CO2
What are 6 enzymes used with human DNA?
1) Polymerases
2) Helicase
3) Ligase
4) Nuclease
5) Primase
6) Topoisomerase
In what direction does DNA polymerase read?
3’ to 5’
In what direction does DNA polymerase print?
5’ to 3’
What are the substrates for DNA polymerase?
Deoxyribonucleotide triphosphates
What is the function of Helicase?
Opens the two strands of DNA
What is the function of Topoisomerase?
Unwinds the DNA - relieves the supercoiling
What does 10 e6 mean?
10 to the power of 6
What does kDa mean?
KiloDaltons - 1000 atomic mass units
Note: 1 Dalton is the mass of a H atom
What does “S” mean?
It stands for Svedberg unit - it refers to the mass and shape of cellular organelles
Note: S values are not additive e.g. ribosome 70S is made up of 50S and 30S
Describe the structure of an mRNA molecule
A long, linear transcript (thats a copy of DNA) with a 5’ CAP and a 3’ Poly A tail
What is the name for the coding regions on mRNA?
Exons
What is the name for non-coding regions on mRNA?
Introns
What is the process in which Introns are removed from mRNA called?
Splicing
At what end is the amino acid on in a tRNA molecule
3’ end
What does degenerate mean in terms of DNA?
That each amino acid can be coded for by more than one codon (but each codon only codes for one amino acid)
Whatis the name for the molecules that are able to initiate gene transcription?
Transcription factors
What do transcription factors do?
1) They bind to specific sequence of 5’ end of first exon called promoter region
2) Collection of transcription factors form transcription complex
3) Helix opens, DNA seperation
4) RNA pol II starts building mRNA
What factors turn off expression of genes?
1) Activation of repressors that inhibit RNA polymerase
2) Prevention of transcription complex formation
3) Enzymes not activated
4) RNA stability
What are mutant alleles?
Pathogenic mutations
What are polymorphyisms?
Benign variations in alleles
What is an out of frame deletion?
Where a one or more nucleotides are deleted but not a whole number of codons
What is an in frame deletion?
Where a whole number of codons are deleted
Which is more serious an in frame or out of frame deletion?
Out of frame as this can affect all codons after the deletion whereas in frame will only affect those deleted
What is a non-sense mutation?
Where the mutation results in the formation of a stop codon which means a gene is not fully transcribed
What is a mis-sense mutation?
This is a single base substitution.
This means it may or may not change the amino acid and if so may not be pathogenic
What is Allelic heterogeneity?
Where lots of different mutations in one gene cause a condition e.g. in cystic fibrosis
What is locus heterogeneity?
Where mutations in different genes give rise to the same clinical condition e.g. hypertrophic cardiomyopathy
What is an automsome?
Any chromosome other than the sex chromomsomes that occur in pairs in diploid cells
What is the definition of homozygous?
Presence of identical alleles at a given locus
What is the definition of heterozygous?
Presence of two different alleles at a given locus
What is the definition of allele?
One or more alternative forms of a gene at a given locus
What is the definition of a locus?
The position of a gene
What is consanguinity?
A reproductive union between two relatives
What is autozygosity?
Homozygosity by descent - the inheritance of the recessive allele through two branches of the same family
What is trisomy?
Where someone has three of one chromosome e.g three of chromosome 21 instead of just the normal two
What is monosomy?
Where there is only one copy of a chromosome not the usual two
How can chromosomal abnormalities be detected?
F.I.S.H
Fluorescence in situ hybridization - this is where DNA probes are used to detect chromosomes
hat does hereditability mean?
The proportion of the aetiology that can be ascribed to genetic factors as opposed to environmental factors
What are the characteristics of multifactorial inheritance?
1) Incidence is greatest in the relatives of the most severely affected
2) The risk is greatest for first degree relatives, it decreases with more distant relatives
3) If there is more than one close relative affected then the the risk for the other relatives is increased.
What is used to identify what alleles cause conditions or increase risk?
Genome wide association studies (GWAS)
These involve doing genetic tests on ill patients and healthy controls and seeing if there are certain alleles that arise more frequently in the ill group
How much energy do you get per gram of carbohydrate, protein, alcohol and lipid?
Carbohydrate - 4kcal/g
Protein - 4kcal/g
Alcohol - 7kcal/g
Lipid - 9kcal/g
What is the Basal Metabolic Rate (BMR)?
The energy required to keep the body alive at rest
Roughly what is the BMR worked out to be?
1kcal/kg/hour
What are the major factors that can decrease BMR?
1) Age (increasing)
2) Gender (women are less)
3) Dieting/starvation
4) Hypothyroidism
What factors can increase BMR?
1) Increased BMI
2) Hyperthyroidsim
3) Low ambient temperature
4) Fever/infection
5) Caffeine/stimulants
6) Pregnancy
7) Lactation
What is the Daily Energy Expenditure?
It is the energy required to support BMR + physical activities + energy to process food intake
(all the energy you require in a day)
What are the three main ways the body stores excess energy?
Triglycerides - 15kg
Protein - 6kg
Glycogen - 200g liver, 150g muscle
What is meant by essential amino acids?
They are the amino acids we need but cannot synthesise in the body - we have to get it from our diet
What is the definition of bioenergetics?
Part of biochemistry concerned with the energy involved in making and breaking chemical bonds in molecules found in biological organisms
If Gibb’s free energy is negative what does this mean?
That a reaction could happen spontaneously - doesn’t mean it will however
What type of molecule are the bases adenine and guanine?
Purines - two carbon nitrogen rings
What type of molecule are the bases cytosine and thymine?
Pyrimidines - one carbon nitrogen ring
What is ATP made up of?
Adenine
Ribose
3 Phosphates
What are adenine and ribose together known as?
Adenosine
What is the bond that is broken in ATP hydrolysis?
Phosphoanhydride
How many phosphoanhydride bonds are there in ATP?
Two
What is the rate limiting enzyme in glycolysis?
Phosphofructokinase
What is the equation for anaerobic glycolysis?
Glucose + 2ADP + 2Pi = 2Lactate + 2ATP + 2H2O + 2H+
What does AMP do in glycolysis?
It is an activator of phosphofructokinase-1
What does citrate do in glycolysis?
Inhibits phosphofructokinase-1
For fatty acids to be used to produce energy they are activated, but by what enzyme?
Fatty acyl-CoA ligase
What does each round of beta oxidation produce?
1 NADH
1 FADH2
1 acetyl-CoA
Where in the Krebs cycle is GTP formed that then forms ATP?
Between succinyl CoA and Succinate
Where is NADH formed in the krebs cycle?
Between:
Isocitrate - alpha-ketoglutarate
Alpha-ketoglutarate - Succinyl-CoA
Malate - Oxaloacetate
Where in the krebs cycle is FADH2 formed?
Between Succinate and Fumarate
What is a free radical?
A molecule with an unpaired electron in the outer shell making it highly reactive
Hydrogen peroxide is a free radical. True or False?
False - It is an oxidising agent in the presence of Fe2+ or other transition metals.
It generates hydroxyl radicals and is lipid soluble
What is the Fenton Reaction?
H2O2 + Fe2+ -> Fe3+ + OH. + OH-
What is the Haner-Weiss reaction?
O2- + H2O2 -> (H+) -> O2 + H2O + OH.
What is the most reactive radical?
Hydoxyl
What produces an organic radical?
When an organic molecule is attacked by a hydoxyl radical
When is organic peroxide produced? (RCOO.)
During lipid degradation
What is the consequence of free radicals?
1) Damage to proteins, lipids and carbohydrates
2) Damage to membranes of nucleus, mitochondria, ER and the cells
3) Increased permeability of calcium, water and sodium
What defences are there against oxygen toxicity?
1) Antioxidant enzymes
2) Cellular compartmentalization
3) Antioxidant vitamins
4) Repair
What are examples of antioxidant enzymes?
1) Superoxide dismutase
2) Catalase
3) Gluthathione peroxidase
What does Superoxide dismutase do?
Turns superoxide to hydrogen peroxide
What does Catalase do?
Converts hydrogen peroxide to water and oxygen
What are the antioxidant vitamins?
Vitamin E
Vitamin C
Carotenoids
What does vitamin E do in terms of free radicals?
Terminates free radical propagation in membranes (Lipophilic)
What does vitamin C do in terms of free radicals?
Reacts with superoxide and hydroxyl anion
Regenerates reduced vitamin E
What is the definition of Homeostasis?
The maintenance of a constant internal environment
In what ways can cells communicate?
1) Hormones
2) Electrical
3) Ions
What is autocrine cell communication?
Cells communicate with themselves
What is paracrine cell communication?
Cells communicate with nearby cells.
Signal diffuses across gap, inactivated locally so doesn’t enter blood stream
Neurotransmitter is an example
What is endocrine cell communication?
Where cells communicate with cells anywhere in the body.
This is done through hormones
What are the endocrine organs?
1) Hypothalamus
2) Pituitary gland
3) Thyroid gland
4) Parathyroid gland
5) Adrenals
6) Pancreas
7) Ovaries
8) Testes
What are the 6 hypothalamic hormones?
1) Gonadotrophin-releasing hormone
2) Growth hormone-releasing hormone
3) Somatostatin
4) Thyrotropin-releasing hormone
5) Corticotropin-releasing hormone
6) Dopamine
What are the 6 Anterior Pituitary gland hormones?
1) Follicle stimulating hormone
2) Lutenising hormone
3) Growth hormone
4) Thyroid stimulating hormone
5) Prolactin
6) Adrendocorticotrophic hormone (ACTH)
What are the 2 posterior pituitary hormones?
1) Oxytocin
2) ADH (Vassopressin)
What type of hormones are: Adrenaline, thyroid hormone, insulin and growth hormone?
Peptide hormones
What type of hormones are testosterone, oestrogen and cortisol?
Steroid hormones
Are peptide hormones fast or slow acting?
Fast
Are steroid hormones fast or slow acting?
Slow
What is an oedema?
Excess water in the intercellular tissue spaces
What is a serous effusion?
Excess water in a body cavity
What is the Henderson-Hasslebalch equation?
pH = pK + log([HCO3-]/[CO2])
What are the main groups of buffers in the body?
1) Intracellular proteins
2) Carbonic acid/bicarbonate
3) Red blood cells
4) Plasma proteins
