IMMS Flashcards
Where is DNA found? What is the structure of DNA?
Nucleus and mitochondria. Double helix with strands in opposite directions. Complementary base pairs between strands. A-T = 2 bonds, C-G = 3 bonds
How is DNA packaged into a chromosome?
DNA coils around histones to form nucleosomes, coils again into supercoils + again into chromosomes
How many chromosomes are there to each cell? What are the two chromosome arms?
46 chromosomes (23 pairs). Long arm (q) + short arm (p(etite)) separated by centromere
Which two dyes are used to stain chromosomes?
- Giemsa = G banding - Quinacrine = Q banding, each band = 6-8 million base pairs
What is the purpose of mitosis?
- To produce 2 genetically identical daughter cells - For growth + to replace dead cells
What stage must a cell be in for mitosis to start? What happens in the synthesis stage for the cell cycle?
Cell must be in interphase. S phase = DNA and centrosome replication
What happens in the first stage of mitosis? Remember IPPMAT
Prophase: - Chromatin condenses into chromosomes - Centrosomes nucleate microtubules + move to opposite poles of nucleus
What happens in the second stage of mitosis?
Prometaphase. - Nuclear membrane breaks down - Spindle fibres begin to form
What are cells called that are permanently in the cell cycle? How about cells that never enter the cell cycle?
Permanently in = labiles. Never in = myocytes
What is the third stage of mitosis?
Metaphase. - Chromosomes line up along equatorial plane
What is the fourth stage of mitosis?
Anaphase. - Sister chromatids separate + pushed to opposite poles of cell
What is the last stage of mitosis?
Telophase. - Nuclear membranes reform - Chromosomes unfold into chromatin - Cytokinesis begins
What is the clinical relevance of studying cells undergoing mitosis?
- Can detect chromosomal abnormalities - Can categorise tumours as benign or malignant - Can grade malignant tumours - lots of mitosis = high grade
Which drugs can be used to disrupt mitosis?
To break mitotic spindle: - Taxol -Vinca alkaloids, e.g. vinblastine To break spindle poles: - Ispinesib To stop anaphase: - Colchicine-like drugs
What is meiosis? How is different to mitosis?
Only occurs in gametes, has 2 cell divisions to create 4 genetically varied haploid daughter cells. It is also not a cycle
What is crossing over? Where in meiosis does it take place?
Crossing over = sorting genes independently. Takes place in Prophase 1. - 1: Interphase G1, Interphase S, Prophase 1, Metaphase 1, Anaphase 1, Telophase 1 - 2: Prophase 2, Metaphase 2, Anaphase 2, Telophase 2, Cytokinesis
What is the difference between sperm and egg production?
Sperm: cytoplasm divides evenly, 4 equal gametes after meiosis 2 Egg: cytoplasm divided unequally to give 1 egg and 3 polar bodies (that apoptose). Meiosis completed at ovulation, meiosis 2 only completed if fertilisation occurs
What is non-disjunction?
The failure of chromosome pairs to separate in meiosis 1 or sister chromatids to separate properly in meiosis 2, e.g. Down syndrome = extra chromosome on 21
What is gonadal mosaicism?
All or part of parental germline is affected by disease mutation, but the parental somatic cells are not affected. Parent = healthy, foetus may have genetic disease. Risk increases with parent age
What are the 3 categories of disease causation?
- Genetic, e.g. Down’s syndrome - Multifactorial, e.g. Spina bifida - Environmental, e.g. scurvy from poor diet
What do phenotype and genotype mean?
- Genotype = genetic constitution of an individual - Phenotype = appearance of an individual = result of genotype + environment
What do the terms allele and polymorphism mean?
- Allele = one of several forms of a gene - Polymorphism = frequent hereditary variations at a locus
What do homozygous, heterozygous and hemizygous mean?
- Homozygous = both alleles the same at a locus - Heterozygous = alleles different at a locus - Hemizygous = only one allele refers to a locus on an X chromosome in a male
What are the 3 categories of genetic disease?
- Chromosomal - Mendelian, e.g. autosomal dominant/recessive, X-linked - Non-traditional, e.g. mitochondrial, imprinting (one allele active, other inactive) + mosaicism (error in cell division, same cells have different genetic makeup)
What are acrocentric chromosomes?
Chromosomes with a short arm
What is autosomal dominant inheritance? How does this compare to autosomal recessive inheritance?
- Autosomal dominant inheritance = disease which is manifest in the heterozygous state. Only one defected gene needed. Affects multiple generations. Both parents can sometimes be unaffected, e.g. gonadal mosaicism, mother has reduced penetrance, mother has variable expression. IF THE TRAIT IS DOMINANT, ONE OF THE PARENTS MUST HAVE THE DISEASE. Example = Huntington’s disease - Autosomal recessive inheritance = disease manifest in homozygous state. Requires 2 defected genes. Affected individuals are in single generation. Chance of having disease = 25%, chance of being carrier = 50%. If a child has an affected sibling, their chance of being a carrier increased to 2/3 (66%), as one possibility removed. Example = Cystic fibrosis
What is X-Linked inheritance?
Caused by mutation in a gene on X chromosome. Never male to male - sons always get X chromosome from mother. Transmitted usually through unaffected female. All daughters from affected males are carriers. Can be recessive (Duchenne’s muscular dystrophy) or dominant (Alpert’s syndrome)
Why can’t males pass on mitochondrial diseases?
Mitochondria = bulky, so can’t fit into sperm
What are amino acids?
- Building blocks of proteins - Side chain often determines polarity (hydrophilicity) or non-polarity (hydrophobicity) - Charge determined by all 3 components (NH2, COOH and R) - 20 different R groups
What are the bonds between amino acids called? How strong are they?
Peptide bonds. Very stable. Cleaved by proteolytic enzymes.
What are proteins?
Large polypeptides, function dependent on structure
What is the primary structure of proteins?
Sequence of amino acids
What is the secondary structure of proteins? What are the 2 secondary structures?
Folding of primary structure. - Alpha helix = H-bonding across folded chain - Beta sheet = bonding between parallel chains. The bonding is due to the sugar-phosphate backbone
What are super secondary structures?
Helix turn helix, beta alpha beta, zinc fingers, leucine
What is the tertiary structure of a protein?
Folding of secondary structure into 3D shape of protein. Forces involved include electrostatic, hydrophobicity, H-bonds and covalent bonds. Bonding due to R group
What is the quaternary structure of a protein?
Multiple protein chains, e.g. haemoglobin has alpha and beta chains
Which forces and bonds are involved from the primary to quaternary structure?
- Van der Waals = weak interactive forces caused by temporary dipole - Hydrogen = dipole between H and O, N or F - Hydrophobic = uncharged and non-polar side chains poorly soluble in water, so are ‘repelled’ = hydrophobic side chains tend to form tightly packed cores in interior of proteins - Ionic = between fully or partially charged groups - Disulphide = between side chains of cisteine (amino acid) residues
How can we determine protein structure?
X-ray diffraction of protein crystals
What is an antibody? What is the portion of an antigen bound to the antibody called?
Antibody binds to antigen. Portion of antigen bound is called epitope
What are the functions of DNA?
- Storing and transferring genetic information - Template and regulator for transcription + protein synthesis - Structural basis of hereditary + genetic diseases
What is DNA like in prokaryotes?
DNA arranged in single chromosomes, no nuclear membrane
What is DNA like in eukaryotes?
DNA in a nucleus, bound to histones (chromatin). During mitosis, chromatin condenses into chromosomes (2 chromatids joined by centromere)
What happens in DNA replication?
- Topoisomerase unwinds DNA + DNA helicase separates H-bonds to expose 2 DNA strands. Replication takes place at both strands - Single stranded binding proteins (SSB’s) coat single DNA strands to prevent reannealing or snapping back together - Primase enzyme then uses original DNA sequence to synthesise short RNA primer. Primers = necessary since DNA polymerase can’t start a nucleotide chain, only extend - DNA polymerase begins to synthesise a new DNA strand (via complementary base pairing using free nucleotides) by extending an RNA primer in 5’ and 3’ direction. Each parental strand copied by one DNA polymerase (lead and lagging strand as chains antiparallel) - As replication proceeds, RNase H recognises RNA primers bound to DNA + removes them by hydrolysing the RNA - DNA polymerase can then fill the gap left by RNase H - DNA replication completed when ligament enzyme joins short DNA pieces (Okazaki fragments) from lagging strand into a continuous strand
What happens in the first stage of transcription?
- Topoisomerase unwinds double helix by relieving the supercoils - DNA helicase then separates the DNA strands, exposing nucleotides - SSBP’s coat single DNA strands to prevent DNA re-annealing
What happens in the second stage of transcription?
- AUG = start codon - Free mRNA nucleotides line up next to their complementary bases on template strand = U-T + C-G - Template runs 3’ to 5’, coding strand runs 5’ to 3’
What happens in the third stage of transcription?
- RNA polymerase joins mRNA nucleotides, forming phosphodiester bonds between them - Forms antiparallel mRNA strand (5’ to 3’) starting at promoter - Stops at stop codon - UAA/UAG/UGA
What is the final stage of transcription?
- Splicing = introns (non-coding) removed to leave exons (coding) - mRNA leaves nucleus through nuclear pores
How does translation work?
- mRNA attaches to 80S ribosome - mRNA strand read 5’ to 3’ - At ribosome, the mRNA sequence (bases read in codons) is used as a template to bind to complementary anticodons on tRNA molecule - tRNA molecules are attached to specific amino acids - Enzymes remove amino acid from tRNA + amino acids are linked together by peptide bond, creating polypeptide chain
What are the features of DNA code?
- Degenerate = many amino acids coded for by more than one codon - Almost universal = all organisms use same code (except a few) - Non-overlapping = each nucleotide read once
What are nucleotides?
- Building blocks of DNA, made from nitrogenous base, sugar + phosphate - Hydrogen bonds between bases - Phosphodiester bonds between sugar and phosphate - Phosphate bonds = source of energy
What are polysaccharides made up of? How do monosaccharides appear?
Monosaccharides. Have one hydroxyl group + generally exist as ring structures. Aldose has an aldehyde, ketose has a ketone
What are the bonds between carbohydrates?
Glycosidic bonds. Hydroxyl group reacts with either -OH or -NH group
What are the 2 glycosidic bonds?
- O-glycosidic bonds form di-,oligo- + polysaccharides - N-glycosidic bonds found in nucleotides in DNA
What are di-, oligo- and polysaccharides?
- Disaccharides = 2 monosaccharides - Oligosaccharides = 3-12 monosaccharides - Polysaccharides = 1000s of monosaccharides joined by glycosidic bonds, e.g. glycogen
Name and explain some common structural anomalies in chromosomes.
- Translocation = portion of chromosome breaks and re-attaches to another chromosome - Inversion = a segment of chromosome is reversed end to end - Deletion = portion of chromosome removed (either out of frame, where sequence shifts so that reading frame of gene is changed, or in frame, where one codon removed so reading frame unchanged) - Duplication = portion of chromosome duplicated
What do consanguinity and autozygosity mean?
- Consanguinity = reproductive union between 2 relatives, increases risk of AR conditions - Autozygosity = homozygosity by descent, i.e. inheritance of same altered allele through two branches of same family
What do penetrance and variability mean? How about sex limitation?
- Penetrance = % of individuals with specific genotype showing expected phenotype - Variability = range of phenotypes expressed by specific genotype - Sex limitation = genes present in both sexes but only expressed in one + remains turned off in the other one
What is the difference between somatic and gonadal mosaicism?
- Somatic mosaicism = genetic fault present at only some tissues in body - Gonadal mosaicism = genetic fault present in gonadal tissue (de novo mutation = genetic alteration present for first time in a family member as a result of a mutation in a germ cell (egg or sperm) of one of the parents
What do these terms mean: - Late-onset - Sex-limited - Predictive testing
- Condition not manifest at birth - Condition inherited one AD pattern that affects one sex more - Testing for a condition in a pre-symptomatic individual to predict chance of developing condition
What does lyonization mean?
Inactivation of an X chromosome, happens in females to prevent twice as many gene products from the X chromosome as males
When referring to mitochondrial inheritance, what do the terms homoplasmy and heteroplasmy mean?
- Homoplasmy = eukaryotic cell whose copies of mitochondrial DNA are identical - Heteroplasmy = denotes mutations which affect only a proportion of the molecules in the cell
Examining a histological section, a pathologist sees a cell undergoing mitosis. The chromosomes are moving towards opposite poles of the cell and there are no nuclear membranes. Which phase of mitosis is this? - A. Anaphase - B. Cytokinesis - C. Metaphase - D. Prophase - E. Telophase
A
Which is the last phase of mitosis? - A. Anaphase - B. Cytokinesis - C. Metaphase - D. Prophase - E. Telophase
B
During mitosis, chromosomes attach themselves to microtubules that propagate from centrosomes. What are these microtubules made of? - A. Actin - B. Cytokeratin - C. Desmin - D. Tubulin - E. Vimentin
D
A 33-year-old woman presents with an unusual rash which the dermatologist biopsies. A dashing pathologist examines a section of skin under the microscope. He observes some cells which he believed are mast cells. Which stain, which turns the granules in mast cells purple, can he use to confirm his hypothesis? - A. Alcian blue - B. Giemsa - C. Haemotoxylin - D. Perls stain - E. Toluidine blue
E
A student examines a section of liver tissue and notices some brown pigment within the liver cells. She wonders if the patient could have haemochromatosis (a form of iron overload). What stain, which turns iron-containing pigment blue, would confirm her hypothesis? - A. Alcian blue - B. Haemotoxylin - C. Iron haemotoxylin - D. Perls stain - E. Van Gieson’s trichrome
D
This pedigree is consistent with which pattern of inheritance? - A. Autosomal dominant - B. Autosomal recessive - C. X-linked dominant - D. X-linked recessive - E. Y-linked
A
A tumour cell in the synthesis phase of the cell cycle begins the process of DNA replication. Which of the substances below splits the two DNA strands apart? - A. Cytosine - B. DNA Polymerase - C. Helicase - D. Topoisomerase - E. Uracil
C
While analysing human genetic material, a geneticist observed that sample A contains single-stranded nucleic acids, and sample B contains double-stranded nucleic acids. Which one of the substances below will be found only in sample A and not in sample B? - A. Adenine - B. Cytosine - C. Guanine - D. Thymine - E. Uracil
E
A forensic scientist is presented with a minute quantity of cellular material from a crime scene. The sample contains only a few cells. In order to produce a sample that is large enough for analysis, he adds the component of DNA to the sample. Assuming that the DNA strands have been split apart, which other substance must be added to catalyse the amplification of the sample? - A. Adenosine - B. DNA polymerase - C. Helicase - D. Topoisomerase - E. Uracil
B
What are the different types of situations where genetic testing is offered?
- Testing for genetic conditions, e.g. diagnostic, predictive - Testing to clarify familial relationships, e.g. paternity testing - Testing to determine identity, e.g. genetic finger printing
What are the different types of genetic tests for genetic conditions? What are they each for?
- Chromosome analysis = tests for abnormalities of chromosome number + structure - Chromosomal microarray analysis = abnormalities of chromosome number + chromosome microdeletions/duplications - Fluorescence in situ hybridization (FISH) = abnormalities of chomosome number + chromosome microdeletions/duplications - Single gene sequencing = single nucleotide changes - Deletion/duplication analysis = whole or partial gene deletions + duplications - Targeted mutation analysis = single nucleotide changes - Multi-gene panels = tests for single nucleotide changes but all others may be picked up by this technique - Whole exome/genome sequencing = tests for single nucleotide changes but all others may be picked up by this technique
What is Sanger sequencing?
- Useful for single gene testing, uses PCR to amplify regions of interest. Very accurate and simple to analyse but time consuming.
What is next generation sequencing (NGS)?
- Multi-gene panels, whole exome/genome. Can sequence whole genome in one day. Fast + moderately accurate but huge amounts of data to interpret
How is the NGS data analysed?
- NGS generates millions of short DNA fragments (reads). Reads are aligned to a reference sequence + can be identified
What are the different types of variants?
- Pathogenic variants = these cause the disease, e.g. mutation in exon 12 causes hypertrophic cardiomyopathy - Variant of unknown significance = require more research, e.g. AAA on exon 12, we know GGG is normal but we don’t know enough about this - Normal variation = genetic info. present into 95% of the population, e.g. 95% have GGG on exon 12 - Benign = coding found in 5% or less of the population (rare), but upon research it’s found that it doesn’t cause disease (not pathogenic)
What are secondary findings?
Additonal findings concerning a patient that are discovered during investigation, but are beyond aims of original investigation
What are targeted panels?
Where we select specific genes to sequence, it means there are fewer variants of uncertain significance
What do these types of variant mean? - Duplications - Deletions (out of frame and in frame) - Variants within regulatory sequence - Non-sense - Mis-sense - Splice site - Tri-nucleotide repeat (and anticipation)
- sections repeating, incorrect protein generated - out of frame = bases removed, causes reading frame of gene to change (frame shift) - in frame = one codon removed (one a.a. lost), reading frame unchanged - coding sequence still intact, but gene itself is switched on or off - non-sense = mutation that produced stop codon, usually results in non-functional protein, e.g. Duchenne’s muscular dystrophy - mis-sense = single nucleotide change results in codon that codes for different a.a. - may or may not be pathogenic, e.g. Sickle cell disease (CAG replaced with CTG) - splice site variants = affects accurate removal of intron - codon repeated. Pathogenic if past certain threshold, e.g. Huntington’s disease = >36 CAG - anticipation = repeats bigger when transmitted to next generation, so earlier symptoms of greater severity
What do allelic and locus heterogeneity mean?
- Allelic heterogeneity = lots of different variants in one gene, e.g. cystic fibrosis - Locus heterogeneity = variants in different genes give the same condition, e.g. hypertrophic cardiomyopathy
What are the three mechanisms of dominance?
- Loss-of-function variants = only one allele functioning - Gain of function variants = increased gene dosage + increased protein activity - Dominant-negative variants = where protein from variant allele interferes with protein from normal allele
The genetic test given depends on the clinical context. Who would be tested in: - diagnostic tests - predictive tests - carrier tests - pre-natal tests - genetic screening?
- patient who has symptoms suggesting particular diagnosis - an at-risk family member = usually for dominant condition - for autosomal recessive + X-linked disorders, couples are tested - performed in pregnancies where there is an increased risk of specific condition affecting fetus - target population, not high risk families
How do we get from a sample to something we can analyse cytogenetically?
- sample - add to culture medium - incubate at 37 C - add colcemid to stop mitosis in metaphase (max. no. of cells) - add hypotonic solution - fix cells + spread onto slide by dropping - staining - banding - karyotyping (putting chromosomes into pairs)
What are the numerical chromosomal abnormalities?
- trisomy, e.g. 47, XX, +21 (trisomy 21 causes Down syndrome) - monosomy, e.g. 45, X - polyploidy = whole set of chromosomes increased, e.g. 69, XXY
How does non-disjunction cause trisomy and monosomy?
Non-disjunction occurs in meiosis. Can occur in M1 (both of chromosomal pair go into one cell, other blank) or in M2 (both chromosomes go into 1 cell, 2 normal and one blank). Therefore, trisomy = 2 + 1 and monosomy = 0 + 1
What are the structural chromosomal abnormalities?
- Translocation - Inversion - Duplication - Deletion
What is reciprocal translocation?
Portions from different chromosomes are swapped. After drawing a cross, it’s clear to see that 1 child will be normal, one will have balanced portions, and 2 children will have unbalanced portions.
What is roberstonian translocation?
This only happens with acrocentric chromosomes (centromere located near end), so p arm = extra small + q arm = extra long. Acrocentric chromosomes are 13, 14, 15, 21 + 22. Example: person will have one 13 and 14 chromsome, and these become stuck together, so they have 45 chromosomes - they are a carrier. If this person reproduces with someone, and they pass on the mixed chromosome along with either 13 or 14, the child would have either two 13’s and three 14’s or three 13’s and two 14’s (an extra chromosome 13 or 14), so will have 47 chromosomes
What is unbalanced arrangement?
This is a deletion of part of a chromosome. Deletion on 5p = Cri du chat, deletion on 15q = Prader Willi
What is F.I.S.H?
- Fluorescence in situ hybridisation. DNA probes labelled with fluorophores are hybridised to the target DNA (has been split into single strands) - Allows us to ‘count’ chromosomes in interphase nuclei. We can look for submicroscopic deletions. - Also helps us identify the origins of marker chromosomes. Assign colours. Can’t do this with G banding
What are microarrays?
Technology that improves the resolution for detection of cytogenetic abnormalities. Assess colour ratios (more patient DNA = red, more control DNA = green).
What is the difference between acquired and constitutional abnormalities?
- Acquired = changes occur during lifetime, restricted to malignant tissue, not heritable - Constitutional = affects all cells of body, heritable
What are the two main mechanisms by which chromosome abnormalities can cause cancer? What is Knutson’s 2-hit hypothesis?
- Fusion genes = breakpoints occur within 2 genes involved, their fusion creates hybrid which gives rise to chimaeric protein - Deregulation = juxtaposition of gene to a regulating gene, altered regulation can result in increased transcription
What is metabolism?
Metabolism refers to the sum of the chemical reactions that take place within each cell of a living organism
What are the two main metabolic processes?
- Anabolic = synthesise larger molecules from smaller components
- Catabolic = break down larger into smaller
What are the 4 main pathways that dietary components are metabolised?
- Biosynthetic (anabolic)
- Fuel storage (anabolic)
- Oxidative processes (catabolic)
- Waste disposal (either)
What is the Cori cycle?
It is a form of gluconeogenesis. It is a metabolic pathway where lactate produced by anaerobic glycolysis in the muscles moves to the liver and is converted to glucose, which then returns to the muscles and is metabolised back to lactate
How are glucose levels controlled?
Insulin from pancreas. Increase in glucose = increase in insulin. Adipocytes = converted to triglycerides, skeletal muscle = converted to glycogen, liver = converted to glycogen
What are the 3 main dietary fuels? Where are they stored?
- Carbohydrates (as glycogen in liver + muscle)
- Protein (muscle)
- Lipids (adipose tissue, fat = most efficient energy store)
What is the Basal Metabolic Rate (BMR)? What increases and decreases BMR?
Estimate of energy needed to stay alive at rest, e.g. respiration. Falls with age, male to female, starvation, hypothyroidism + decreased muscle mass (muscle cells require lots of energy to maintain). Increases with body weight, hyperthyroidism, cold environment + fever
What happens in starvation?
- Insulin switched off, glycogen stores used up.
- Gluconeogenisis from non-carbohydrate stores, e.g. amino acids and lactate
What are the dangers of re-feeding syndrome?
Re-feeding syndrome happens after a period of starvation. Insulin re-distributes phosphate, potassium, magnesium etc. Carbohydrate is used as main fuel again, requires phosphate + thiamine for TPP in Krebs cycle, can become thiamine deficient
What are micronutrients? What role do they play within the body?
Micronutrients = trace elements + vitamins. Used as co-factors in metabolism, e.g. TPP (Vitamin E1) required for acetyl co-enzyme A to function in Krebs cycle, gene expression + structural components
In multifactorial inheritance, what are the 3 ways of identifying a condition that has a genetic component?
- Family studies
- Twin studies
- Adoption studies
What are family studies? What would be true if it was a multifactorial condition?
Compare incidence of disease amongst relatives of an affected individual with general population. In multifactorial condition:
- Risk of condition in relatives greater than risk in general population
- Risk varies directly with degree of genetic relationship
- Risk varies with severity of affected individual’s illness
- Risk varies with number of relatives affected
What are twin studies? What is the concordance rate?
- Compare genetically identical (monozygotic) twins with non-genetically identical (dizygotic) twins
- Concordance rate = % of twin pairs studies that both have condition. Gives rough figure for hereditability of multifactorial disorder
- If condition has genetic component, expect concordance rate of MZ twins to be higher than DZ twins. There will still be a high risk for separated MZ twins if genetic, as environmental factors redundant
What are adoption studies?
Adopted children of parent with multifactorial disease have high risk of developing disease. Normal biological parents or adopting parent with multifactorial disease = low risk
What is hereditability?
Proportion of aetiology (factors leading to development of disease) that can be ascribed to genetic factors as opposed to environmental
What are the characteristics of multifactorial inheritance?
- Incidence of condition greatest among relatives of most severely affected individuals
- Risk greatest for first degree relatives
- More than one 1 relative affected = increased risk for other relatives
- If condition more common in particular sex, relatives of affected individual of less frequently affected sex = higher risk than relatives of affected individual of more frequently affected sex, e.g. women in high-risk family more at risk than men in general population, even if men affected more generally
What is the Liability/Threshold model?
Shows increasing incidence of disease in relatives compared to general population. Closer the relationship = greater shift to right
What is ATP? What is it made of? What happens in ATP hydrolysis?
Major source of energy for cell. Made of adenine, 5-carbon ribose + 3 phosphate groups.
ATP + H20 = ADP + phosphate + H+
Glucose is used by ALL cells to generate ATP during respiration
What are the overall products of glycolysis?
1 molecule of glucose produces 2x ATP, 2x NADH + 2x pyruvate.
Especially learn the steps which use and release ATP
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What happens in the first step of glycolysis?
Glucose goes to glucose-6-phosphate. Enzyme is hexokinase or glucokinase in liver. ATP to ADP + Pi
What happens in the second step of glycolysis?
Isomerise glucose-6-phosphate to fructose-6-phosphate via phosphoglucose isomerase.
What happens in the third step of glycolysis? Why is this step important?
Fructose-6-phosphate to fructose-1,6-bisphosphate via phosphofructokinase and ATP to ADP + Pi.
Phosphofructokinase is the rate-determining step
What is the fourth step of glycolysis?
Fructose-1,6-bisphosphate converted to dihydroxyacetonephosphate and glyceraldehyde-3-phosphate (type of triose phosphate) via aldolase. Dihydroxyacetonephosphate then converted to glyceraldehyde-3-phosphate via triose phosphate isomerase. We have 2x glyceraldehyde-3-phosphate
What is the fifth step of glycolysis?
Oxidation of 2x glyceraldehyde-3-phosphate to 2x 1,3-bisphosphoglycerate via glyceraldehyde-3-phosphate dehydrogenase (2 Pi in and 2 NADH produced). 2x 1,3-bisphosphoglycerate to 2x 3-phosphoglycerate via phosphoglycerate kinase 2 ADP to 2 ATP (x2 so 4 ATP produced)
What is the final step of glycolysis?
2x 3-phosphoglycerate to 2x 2-phosphoglycerate via phosphoglyceromutase. 2x 2-phosphoglycerate to 2x phosphoenolpyruvate via enolase and removal of water molecule. 2x phosphoenolpyruvate to 2x pyruvate via pyruvate kinase and 2x ADP to ATP.
What is the summary of products and reactants in glycolysis?
Draw out glycolysis (remember about enzymes).
What happens to pyruvate?
- Aerobic = Krebs cycle
- Anaerobic = lactate
Draw out the Krebs cycle.
Occurs in mitochondrial matrix. Acronym for reactants: can I keep selling socks for money officer?
What is oxidative phosphorylation?
- Electron transport chain, takes place in the inner mitochondrial membrane
- NADH + FADH oxidise to deliver electrons to power proton pumps. Complex I removes electrons from NADH, Complex II removes electrons from FADH. Complexes III, IV and cytochrome C donate these electrons to cytochromes containing iron
- Work via electrochemical gradient, H+ pumped into intermembrane space, build up this gradient. H+ ions then flow down gradient, through ATP synthase to form ATP
- Electrons then transferred to O2 (acts as final electron acceptor) to split to form water
- Total ATP from one molecule of glucose is 34 ATP, one molecule of NADH = 3 ATP, one molecule of FADH = 2 ATP
How are ingested lipids absorbed into cells?
- Lipids emulsified by bile salts in small intestine, forming micelles
- Lipases degrade triacylglycerols
- Fatty acids + other products taken up by intestinal mucosa + converted into triacylglycerols
- Triacylglyerols converted, with cholesterol + apoproteins, into chylomicrons
- Chylomicrons move through lymphatic system + bloodstream to tissues
- Lipoprotein lipase releases fatty acids + glycerol
- Fatty acids enter cells + oxidised as fuel or reessterifed for storage
Before fatty acids are used as energy store, they must be activated in the cytoplasm. How is this done?
What happens to the acyl Co-A if it has less than 12 carbons or more than 14 carbons?
- <12 carbons = can diffuse through membrane to mitochondria
- >14 carbons = takes through mitochondrial membrane using carnitine shuffle
Draw out fatty acid oxidation.
Fatty acid oxidation is the production of ATP from fat consumption + occurs in the mitochondria
What happens to the product, acetyl Co-A?
- Krebs cycle
- If there are high rates of fatty acid oxidation, no need for all acetyl Co-A, so converted to ketones
Which factors affect ketogenesis (forming ketones)?
- Release of free fatty acids
- Demand of ATP, e.g. more ATP required = more Krebs = less ketones
- Fat oxidation dependent on amount of glucagon (activation) or insulin (inhibition)
- Low conc. of glycerol-3-phosphate in liver = increased ketone production
What is active transport? What are the two types?
- Active transport requires input of energy, low to high:
- Primary = directly uses source of energy, usually ATP
- Secondary = transport of substance against gradient coupled to transport ion which moves down its gradient (co-transport), uses energy from generation of ions
Name a couple of drugs that target membrane receptors.
- Proton pump inhibitors
- Loop diuretics
What is homeostasis?
Maintenance of a constant internal environment, e.g. temperature
What are the 5 types of cell junction?
- Tight junction = seals neighbouring cells together in an epithelial sheet to prevent leakage of molecules between them
- Adherens junction = joins an actin bundle in one cell to a similar bundle in a neighbouring cell
- Desmosome = joins the intermediate filaments in one cell to those in a neighbour
- Gap junction = allows the passage of small water-soluble ions + molecules
- Hemidesmosome = anchors intermediate filaments in a cell to the basal lamina
What are the 4 types of communication?
- Autocrine
- Paracrine
- Endocrine
- Exocrine
What is autocrine communication?
- Messenger molecules bind with receptors in the cell where they are produced. Cells ‘talk’ to themselves, e.g. chemical messengers
What is paracrine communication?
- Cells communicating to neighbouring cells a short distance away. Signal diffuses across gap between cells, doesn’t enter bloodstream
What is endocrine communication?
- Cells communicating to other cells in the body, via secretions in the blood, e.g. thyroid, pancreas
What is positive feedback?
Amplification of signal
What is negative feedback?
End product in turn reduces stimulus of process, basis for homeostasis
What are phospholipids made of?
Glycerol, 2 fatty acids + phosphate group (+ either serine, choline or inositol). Fatty acid tails = hydrophobic, phosphate head = hydrophilic
What is the diffusion potential?
Diffusion potential is the potential difference generated across a membrane when an ion diffuses down its concentration gradient. Increase in ion conc. on one side of membrane = increase in tendency for ion to diffuse in one direction, so a larger diffusion potential is required to prevent further net diffusion. Example: Na+ conc. intracellular = 14mmol/l, Na+ conc. extracellular = 142mmol/l. Na+ diffuses to intracellular, so diffusion potential = +61.87mV (intracellular becomes depolarised). Number generated from an equation.
What are the prominant electrolytes in intracellular and extracellular fluid? Can all fluid losses be measured?
- ICF = potassium
- ECF = sodium, chloride, bicarbonate + Ca2+ especially in heart and muscles
Fluid losses either sensible (measured, e.g. urine) or insensible (cannot be measured, e.g. evaporation)
What is extracellular fluid comprised of?
Extravascular fluid and intravascular fluid (plasma = circulates as extracellular component of blood). Extravascular fluid comprised of interstitial fluid (surrounds cells but doesn’t circulate) and transcellular (makes up CSF, digestive juices, mucus etc.)
60% of the body’s weight is water. How is this water spread?
Total body water = 42L (60% of 70kg). ICF = 28L, ECF = 14L. Intravascular fluid = 3L, interstitial = 11L
What do these terms mean?
- Osmosis
- Osmolality
- Osmolarity
- Osmotic pressure
- Oncotic pressure
- Hydrostatic pressure?
- Net movement of solvent molecules through semipermeable to higher solute conc. (lower water conc.)
- Measure number of dissolved particles per L of fluid, higher osmolality = greater amount of substance dissolved
- Measure number of dissolved particles per kg of fluid
- Pressure applied for a solution, by a pure solvent, required to prevent inward osmosis, through a semipermeable membrane
- Form of osmotic pressure exerted by protein that tends to pull fluid into its solution = water moves from interstitial fluid into plasma
- Pressure difference between capillary blood (plasma) + interstitial fluid = water and solutes move from plasma into interstitial fluid
What are the causes and effects of dehydration?
- Causes: water deprivation, vomiting, diarrhoea, burns, heavy sweating, diabetes insipidus (too little ADH, loads of urine), diabetes mellitus + drugs
- Consequences: thirst, inelastic skin (won’t go back down after pinching), sunken eyes, raised haemocrit (viscosity of blood), weight loss, confusion + hypertension
What are the causes and consequences of water excess?
- Causes: High intake/decreased loss of water, excess ADH
- Consequences: Hyponatraemia (low sodium levels), cerebral over-perfusion (due to high blood volume and thus pressure, causes headaches, confusion + convulsions)
What happens when there is excess water in the ECF?
Decreases ECF osmolarity. Osmoreceptors in hypothalamus detect this and inhibit the release of ADH from the posterior pituitary. Increased urine volume
What is serous effusion? What is an oedema? What are the different types of oedema?
- Serous effusion = excess water in body cavity (fluid-filled space that holds and protects internal organs). Example = pleural effusion, results from disruption of balance between hydrostatic and oncotic forces in visceral and parietal pleural vessels
- Oedema = excess water in intracellular tissue space. Types:
- Inflammatory
- Venous
- Lymphatic
- Hypoalbuminaemia
What is an inflammatory oedema?
Proteins leak out due to increased vascular permeability. They bring water, so dilutes toxins.
What is a venous oedema?
Due to increased venous pressure or venous obstruction from a thrombus
What is a lymphatic oedema?
Blockage in lymphatic system, prevents fluid from draining
What is a hypoalbuminaemic oedema?
Lower oncotic pressure. Lower albumin levels
What are enzymes? What are the two types of enzyme?
- Catalysts = provide alternative reaction pathway with lower Ea
- Enable reactions to occur that otherwise would not be able occur at body temperature + conditions
- Bind to reactants + convert them to products, release products + return to original form
- Speed up reactions + provide a way to regulate rate of reaction
- Can alter concentration of substrates, products, inhibitors or activators
- Rate of reaction affected by temperature, surface area, pressure/concentration, presence of enzymes
Two types:
- Isoenzymes: enzymes that have different strcuture + sequence but catalyse same reaction
- Coenzymes: cannot catalyse a reaction but help enzymes to do so - bind with enzyme protein molecules to form active enzymes
Autosomal recessive
Autosomal dominant
Sex-linked
What are the stages 1-6?
1) Anaphase
2) Telophase
3) Prophase
4) Metaphase
5) Cytokinesis
6) Interphase
The image is a sample obtained from a patient who died after an episode of chest pain. Which of the following statements is true?
- A. This is cardiac muscle
- B. This is smooth muscle
- C. The nuclei are in register
- D. The myofibrils are in register
- E. It is from the myometrium
D
Which enzymes catalyses this part of the aerobic glycolysis pathway?
- A. Aldolase
- B. Phosphfructokinase
- C. Phosphglucose isomerase
- D. Phosphoglycerate kinase
- E. Triose phosphate isomerase
D
Which of the following statements about this epithelium is true?
- A. It can stretch
- B. It is keratinized
- C. It lacks a basement membrane
- D. It lines the trachea
- E. It secretes mucus
A
What is most likely represented by the x axis on the graph?
- A. Renin
- B. Sodium concentration
- C. Plasma osmolality
- D. Blood pressure
- E. Potassium concentration
C
A diagramatic representation of the relative amounts of intracellular actions and anions is shown. Which of the following are most likely represented by the letters Y and Z?
- A. Na and K
- B. K and lactate
- C. Na and lactate
- D. Na and HCO3
- E. K and HCO3
E
Picture of pedigree charts.
Picture of cell.
What are the different parts of mitochondria? What are their functions?
Table of cell structures and their function.
What is lipofuscin, lipid and glycogen?
What does the phospholipid bilayer contain? What is its function?
What are the three modes of secretion?
Diagram of RAAS.
What is the karytoype?
Number + visual appearance of the chromosomes in the nuclei of an organism or species
What is Mendel’s second law (law of independent assortment)?
What are some genetic, multifactorial and environmental diseases?
What is an acid? What is a base? How about strong and weak acids/bases? What is a buffer?
What is the Henderson-Hasselbach equation? What are some body buffer systems?
What is a reactive oxygen species? What is the Fenton reaction? What is the Haber-Weiss reaction?
What you need to know from IMMS histology.
