MCGB Revision Lecture 1b Flashcards

(143 cards)

1
Q

DNA replication is

A

sem-conservative

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2
Q

DNA replication is a 3 stage process

A
  • initiation
  • elongation
  • termination
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3
Q

in DNA replication the chain grows in a

A

5’ to 3’ direction

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4
Q

what drives DNA replication

A

pyrophosphate hydrolysis

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5
Q

outline DNA replication

A

1) Topoisomerase unwinds the DNA and Helicase breaks the hydrogen bonds between the parental double helix
2) DNA primase synthesises RNA primers, which allow DNA polymerase to bind to single strand
3) Leading strands is read in the 3’ to 5’ direction and synthesised continuously in the 5’ to 3’ direction by DNA polymerase
4) Lagging trans is synthesised discontinuously- primase synthesises numerous short primers which are extended by polymerase to form Okazaki fragments
5) After the primer is replaced by DNA, DNA ligase joins the Okazaki fragments

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6
Q

termination of DNA replication occurs when

A

two facing repclication forks meet and DNA ligase joins the final frgaments

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7
Q

telomeres

A

repetitive DNA sequences that protect the integrity of chromsosmes

  • prevents degradation of coding material
  • ensure genomic stability
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8
Q

telomerase

A

prevents telomeres shortening

  • -> when there is not enough DNA for primers (oligonucleotides) to bind to = uneven length of both strand s of DNA= degradation of longer strand
  • -> telomerase lengthens the DNA so primers can bind- preventing loss of DNA
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9
Q

Hayflicks constant

A

maximum number of times a cell can divide without telomerase = 61.3 in human cells

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10
Q

mitosis order

A
prophase
prometaphase
metaphase
anaphase
telophase
cytokinesis
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11
Q

mitosis: prophase

A
  • Nuclear envelop disintegrates
  • Chromosomes condense
  • Mitotic spindle starts to forms
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12
Q

mitosis: prometaphase

A

spindles form from centrioles and connect with kinetochore of chromosomes

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13
Q

mitosis: metaphase

A

chromosomes randomly line up at the metaphase plate

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14
Q

mitosis: anaphase

A
  • Kinetochore microtubules pull chromatids towards the poles

- Go to different poles (now become chromosomes (not called chromatids anymore)

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15
Q

mitosis: telophase

A
  • Spindle disappears
  • Nuclear membrane reforms
  • Nucleolus reappears
  • Chromosomes decondense
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16
Q

mitosis: cytokinesis

A

cleavage of daughter cells with equal number of chromosomes

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17
Q

mitosis overview

A

cell division for somatic cells
–> Production of two identical daughter cells
o Same number of chromosomes content as parental cell
- Important during development (~50 mitotic rounds) and mitotic growth (epidermis, mucosae, bone marrow, spermatogenesis)

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18
Q

in humans the haploid cells created by meiosis are

A

sperms and eggs

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19
Q

meiosis is

A

division for germ line cells

  • Oogenesis
  • Spermatogenesis
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20
Q

meiosis produces

A

4 non-identical cells - half chromosome content of parental cell (2n–> n)

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21
Q

how many rounds of replication and division in meiosis

A
  • one round of replication

- two rounds of division- to separate sister chromatids

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22
Q

outline meiosis I

A

1) Prophase I: 1) Chromosomes begins to condense and pair up (homologous chromosomes (from mums and dad) will look for each other)

2) Metaphase I: spindle begins to capture chromosomes and move them towards the centre of the cell- metaphase plate
- Each chromosome attaches to microtubule from just one pole of the spindle
- Homologous pairs not individual chromosomes line up for separation.

3) Anaphase I: homologues are pulled apart and move apart to opposite neds of the cell
- Sister chromatids of each chromosome remain attached to one another and
don’t come apart

4) Telophase I: chromosomes arrive at opposite poles of the cell
- Cytokinesis occurs at the same time as telophase I
- Cleavage- formation of two haploid non-identical daughter cells

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23
Q

when does homologous recombination occur and how

A

during Prophase I via crossing over

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24
Q

explain crossing over

A

o DNA is broken at the same spot on each homologue and exchange part of their DNA
o Crossing over occurs as chiasmata- cross shaped structures where homologues are linked together
o Chiasmata keep homologues connected
o Can have multiple cross overs

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25
meiosis II
Cells move from meiosis I to II without copying their DNA. Meiosis II is a shorter and simpler process than meiosis I basically ‘mitosis for haploid cells’. - Cells that enter meiosis II are made in meiosis I - Cells are haploid and have one chromosome from each homologues pair - But chromosomes still consists of two sister chromatics - In MII sister chromatids separate, making haploid cells with nonduplicated chromosomes
26
outlines meiosis II
1) Prophase II: Chromosome condense and nuclear envelop breaks down- if needed - Centrosomes move apart - Spindle forms between them - Spindle microtubules begin to capture chromosomes - Two sister chromatids are captures by microtubules from opposite spindle poles 2) Metaphase II: the chromosomes line up individually along the metaphase plate. 3) Anaphase II: sister chromatids separates and are pulled towards opposite poles of the cell 4) Telophase II: nuclear envelopes form around each set of chromosomes and the chromosomes decondense. - Cytokinesis splits the chromosome set into new cells - Forming 4 haploid cells in which each chromosomes has just
27
describe oogenesis
1) Primary oocyte (2n) divides to form 1 secondary oocyte (1) and 1 polar body 2) The secondary oocyte (n) divides to form ovum (n)
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polar bodies in oogenesis
4 polar bodies in total produced (2 from original polar body and one from secondary oocyte
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describe spermatogenesis
1) Primary spermatocyte (2n) divides to form 2 secondary spermatocyte (n) 2) Secondary spermatocytes divide to form 4 spermatids 3) 4 spermatids mature into sperm
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importance of meiosis
introduces variation
31
meiosis introduces variation via
- random segregation - independent assortment - crossing over
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non-disjunction
results in variations in chromosome number, which can occur in both meiosis I and II - e.g. aneuploidy
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which meiosis is non-disjunction most harmful in
meiosis I | - non of the cells face a correct number of chromsomes
34
sources of DNA damage
endogenous exogenous
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endogenous sources
- replication stress - reactive oxygen species - intrinsic instability of DNA (hydrolysis, oxidation, methylation)
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exogenous DNA damage
- chemical radical - ionising irradiation - UV light
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name some types fo DNA damage
``` ss break mismatch damaged base ds break intrastrand cross link interstrand crossline ```
38
DNA damage response (3)
- senesence - proliferation - apoptosis
39
replication stress defined as
‘Inefficient replication that leads to replication fork slowing, stalling and/ breakage.’
40
Replication stress can be caused by:
1) Replication machinery defects 2) Replication fork hindrance • Forward and backward slippage • e.g. Trinucleotide repeats 3) Defects in response pathway
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1) Replication machinery defects
* Misincorporation by DNA polymerase | * Proofreading error by DNA polymerase
42
2) Replication fork hindrance
Repetitive DNA can lead to fork slippage Forward slippage (deletion mutation) • New strand has an extra nucleotide (A) • Newly synthesised strand loops out Backward slippage (insertion mutation) • New strand is missing a nucleotide (A) • Template strand loops out
43
example of a disease caused by replication fork progression hindrance
Fork slippage leads to trinucleotide expansion e.g. Huntington’s (backward slippage) * HTT gene * Trinucleotide CAG repeats- polyglutamine repeats
44
increased CAG repeats in Huntington's causes
neurone degeneration
45
replication machinery defects
DNA polymerase has a 3’ to 5’ DNA exonuclease domain and proofreads leading to the right nucleotide in its place. However, sometimes mismatches occur. Other enzymes involved in the replication can also be faulty such as topoisomerase or helicase.
46
defects in response pathway
repair doesn't occur at the checkpoints
47
DNA repair techniques
1) Base excision repair | 2) Nucleotide excision repair
48
Double strand break repair mechanisms (high energy radiation)
- non-homologous end joining | - homologous recombination (better)
49
what can proteins act as
RITE
50
R
receptors
51
I
ion channels
52
T
transporters
53
E
enzymes
54
structural unit of proteins
amino acids
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what joins amino acids
peptide bonds
56
properties of peptide bond
planar rigid stereosiosmerism
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amino acids are classified according to their
R groups properties
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pKa is a
pKa value is one method used to indicate the strength of an acid. pKa is the negative log of the acid dissociation constant or Ka value. A lower pKa value indicates a stronger acid. That is, the lower value indicates the acid more fully dissociates in water.
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if there is a negatively charged froup
loss of hydrogen has occured
60
if an R group can donate hydrogen
it is acidic
61
lower pKa
more acidic
62
if pH
R group is protonated
63
if pH> pKa
R group is deprontonated
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pKa equation
pKa = -log (Ka)
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pI
isoelectric point
66
isoelectric point
pH at which there is no overall net charge
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if pH
protein protonated
68
if pH>pI
protein is deprotonated
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protein folding
- primary - secondary - tertiary - quaternary
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primary structure
linear amino acid sequence
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secondary structure
local spatial arrangement of polypeptide backbone to for an alpha helix or beta pleated sheet
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tertiary structure
3D configuration with further folding
73
quaternary structure
different polypeptides join, sometimes with a prosthetic group
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bonds in primary structure
Covalent - peptide - disulphide (between cysteine)
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bonds in secondary structure
- hyrogen - peptide - disulphide
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bonds in tertiary structure
- hydrophobic bonds - hydrogen bonds - ionic bonds - van der waal forces - disulphide
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bonds in quaternary structure
- hydrophobic - hydrogen - ionic - van der waals - disulphide
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fibrous proteins
Long and anrrow- role in providing structural support
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fibrous protein solubility
mostly insoluble
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sequence of amino acids in fibrous proteins
repetitive
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stability of fibrous proteins
less sensitive to changes in heat and pH
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examples of fibrous proteins
collagen and keratin
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globular proteins
rounded/spherical- role is functional (catalysts and transport)
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solubility of globular proteins
soluble
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sequence of amino acids in globular proteins
irregular
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stability of globular proteins
more sensitive to changes in heat and pH
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examples of globular proteins
hb, insulin and catalse
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enzyme models
- lock and key | - induced fit
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enzymes
lower the activation energy required for a reaction to occur
90
which equations can be used to predict the Vmax and Km of an enzyme
Michaelis- menten and Lineweaver Burk Plot
91
how to recognise Michaelis menton
hyperbole shape | - Velocity vs [substrate]
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how to recognise Lineweaver Burk plot
straight lines
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Vmax
rate of reaction when the enzyme is fully saturated by substrate, indicating that all the binding sites are constantly reoccupied
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Km is the
substrate concentration that give gives half Vmax
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the lower the Km
the higher the affinity for the substrate
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types of enzyme inhibition
competitive non-competitive
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competitive
inhibitor binds to active site - directly blocking the active site for the substrate
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non-competitive
changes the shape of the active site by bnidnign to allosteric site
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inhibitors are molecules which
slow down of prevent enzyme reaction. they can be irreversible or reversible
100
reversible competitive inhibitors
adding more substrate can override the effect on the enzyme | - as a result the Vmax is unaffacted but the Km will increase
101
reversible non-competitive inhibitor
the Vmax decreases but Km is unaffected
102
what can cause irreversible damage to enzymes
denaturation, pH and temp
103
energy is the capacity to
do work and exists in may forms
104
food has stored
chemical enegry
105
humans require energy for
- biosynthesis work - transport work - mechanical worj - electrical work
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what is the official SI unit of food enegry
Kj
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what do doctors usually use to explain energy in food
calories
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1kcal is equal to how many KJ
4.2KJ
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catabolism
catabolism breaks large molecules into smaller ones
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anabolism
anabolism builds complex molecules from simpler ones
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what are essential components of the diet
- carbohydrates - proteins - fats - mineral - vitamins - fibre
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examples of carbohydrates
starch, sucrose, fructose, glucose, maltose, glycogen
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monosaccharides
glucose fructose galactose
114
disaccharides
maltose lactose sucrose
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maltose
glucose-glucose
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lactose
galactose-glucose
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sucrose
glucose-fructose
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list the 9 essential amino acids (pneumonic)
``` If Learned This Helpful List May Prove Truly Valuable ``` ``` Isoleucine Leucine Threonine Histidine Lysine Methionine Phenylalanine Tryptophan Valine ```
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why may children and pregnant women require amino acids added to their diet
high rate of protein synthesis | e.g. need extra arginine, tyrosine and cysteine
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fat contains less
oxygen compared to hydrogen than carbohydrates or proteins
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fat has less oxygen and this means
it becomes more reduced and yields more oxygen when oxidised
122
fats provide a source of
essential fatty acids ( linoleum and linolenic) which can't be synthesised in the body
123
minearls
required to maintain ion gradients, calcium and phosphorus for structure, signalling, enzyme cofactors (iron, magnesium, copper, zinc, manganese) and haemoglobin
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vitamins
e.g. A, D, K, C, folate, B6 essential for life and can lead to deficiency diseases
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Vitamin A deficiency
xerophthalmia
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Vitamin D deficiency
rickets
127
Vitamin K deficiency
defective blood clotting
128
Vitamin C deficiency
scurvy
129
folate deficiency
neural tube defects and anaemia
130
B6 deficiency
dermatitis
131
BMI calculation
weight (kg)/ height (m^2)
132
obesity is due to
excessive energy intake which is stored in adipose tissue
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when does obesity occur
when energy intake> energy expenditure
134
what can obesity cause?
T2D CHD Osteoarthritis Cancers
135
underweight BMI
<18.5
136
normal BMI
18.5- 24.9
137
overweight BM
>25
138
obese BMI
>30
139
severely obese BMI
>40
140
main two conditions which occur in malnutrioned children
- Marasmus | - Kwashiorkor
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Marasumus characterised by
not having too low protein (non oedema)
142
outline marasmus
- calorific deficiency and protein deficiency - children under the age of 5 - muscle wasting - emaciated - loss of body fat - thin hair - diarrhoea - anaemia
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outline kwashiorkor
- protein deficiency - children displaced from breastfeeding - ascites and oedema (starling forces`) - hepatomegaly (fat deposition- causes abdominal distension) - thin limbs