L4 & L5 : Molecular Adaptations for Survival Flashcards

(57 cards)

1
Q

How can extremophiles be categorised?

A

By specific conditions (eg. thermophile)
Extreme environments may pose combined challenges (eg. haloalkaliphiles)
Extremophiles adapt, defend, exploit

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2
Q

As an example, what challenges do extremophiles face in deep sea vents?

A

High pressure
High temperature
Lack of light

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3
Q

What are important functions of the cell membrane in extremophiles?

A
  1. Barrier function to prevent unregulated in/outward transport
  2. Regulates proton transport and maintains gradients for energy production
  3. Ensure membrane fluidity for protein function
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4
Q

How does membrane fluidity change with temp and pressure?

A

Increases at high temps

Decreases at low temps or high pressure

Affects protein mobility and membrane function

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5
Q

How do extremophiles adapt the cell membrane?

A

Different membrane compositions to alter fluidity and stability
Maintain function under extreme conditions

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6
Q

How do archaeal thermophiles decrease membrane fluidity?

A

Isoprenoid ether lipids
- Liquid crystalline
- Provide low permeability from 1-100 deg

Tetraether-linked lipids
- Increase rigidity
- Can span entire membrane

  • Less space between phospholipids
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7
Q

How does piezophilic Colwellia increase membrane fluidity

A
  • More polyunsaturated FAs in phospholipids
  • Express delta-9-acyl phospholipid desaturase to introduce douvle bonds
  • No cis to trans isomerases
  • Metabolism adapted to create required fatty acids
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8
Q

Why is proton impermeability important for acidophiles?

A

Preserves proton gradient
- Used for ATP synthesis
- Prevents cytoplasmic acidification

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9
Q

How does S. acidocaldarius lower proton permeability?

A

Thermophilic acidophile

Lipids form liposomes with low proton permeability across range of temperatures

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10
Q

How do acidophiles maintain membrane potential?

A

Mesophile typically have ~-73 mV

Degrade weak acid uncouplers
- Prevent disruption of pH balance
Actively pump in K+
- Maintain positive intracellular environment against high external proton conc

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11
Q

How do alkaliphiles use proton gradients as source of energy?

A

Rely on proton-motive force for ATP synthesis

  • Use ATP synthase to import protons and maintain neutral internal pH
  • Mutations give adaptations that allow enhanced ability to bind H+ at high pH
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12
Q

How do alkaliphiles create localised lowered extracellular pH

A
  • Make and secrete acids produced through fermentation
  • Produce acidic, negative components for cellular surface
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13
Q

How are proteins structurally adapted in extremophiles?

A
  • Denser core and tighter packing in high pressure environment
  • Surface residues of proteins may be altered to cope with altered internal conditions
  • Different chaperones required for different conditions to maintain stability under stress
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14
Q

How are psychrophile enzymes adapted?

A
  • More flexible active sites
  • Allows function despite low kinetic energy
  • Also results in lowered substrate affinity and decreased specificity
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15
Q

Why is Fe2+ oxidation exploited by acidophiles but not in neutral pH?

A

At neutral, Fe2+ rapidly oxidises to Fe3+
- Unusable
Acidic conditions stabilise Fe2+
- Viable energy source

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16
Q

How do psychrophiles exploit increased oxygen solubility at low temps?

A

Upregulate aerobic metabolism enzymes
Use oxygen-dependent acyl desaturases to maintain membrane fluidity

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17
Q

Risks of lower temps and increased oxygen solubility? How do psychrophiles cope?

A

Increased ROS production

Decrease production of oxidisable residues
Deletion of ROS-producing pathways
Upregulate SOD and glutathione synthetase

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18
Q

Why are extremophiles hard to cultivate?

A

~1% of bacteria in samples are cultivatable

Many require:
- Complex growth conditions
- Specific symbiotic factors
- Often grow very slowly (eve in optimum)

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19
Q

How can extremophiles be studied using bioinformatics?

A

Phyla can be classified on basis of 16S rRNA genes

High throughput sequencing allows:
- Bioinformatic analysis
- Predict gene function based on homology
- Infer metabolic pathways

Large proportion of genes may have no predicted function

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20
Q

What are challenges of adapting to environments?

A

Evolution suited to particular habitat with limited variation

Acute or chronic respone changes may not be suitable or sustainable

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21
Q

Why is oxygen important?

A

Terminal electron acceptor of aerobic respiration
Complex IV (cytochrome oxidase) of ETC reduces oxygen

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22
Q

What challenges do hypoxic environments pose to organisms?

A

Limited oxygen availability
Reduced aerobic respiration
Need for rapid or sustained physiological and molecular adjustments

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23
Q

How does oxygen concentration vary in different environments?

A

At sea level:
21% O2
0.03% CO2

Underground
7.2% O2
6% CO2 (lower ratio)

Higher altitude
= decreased pressure
= same proportions but lower concentrations

24
Q

What are some general responses to cope with hypoxia?

A
  1. Reduce need for oxygen
    - decrease metabolic rate
    - switch to anaerobic metabolism
  2. Improve delivery of oxygen
    - changes to cardiovascular and respiratory system
  3. Modify oxygen-sensing machines
25
What does acute response entail?
Immediate - nervous system mediated
26
What does chronic response entail?
Acclimatisation - changes in gene expression - altering behaviour and number of cells
27
What does adaptation response entail?
Improve survivability (including next gen) - Changes in allele frequency - Spontaneous mutations/admixture - Strategies differ between populations
28
Examples of established high altitude human populations and adaptability?
Tibetan plateau - largest, most studied Andean - most recent, seem less well-adapted Ethiopian highlands - longest, least studied Studies typically compare genetics with local sea-level populations
29
What is the main physiological controller of breathing rate?
Ventilatory drive Primarily regulated by CO2 levels and pH Via central chemoreceptors in brainstem
30
How is breathing regulated in response to pH changes?
Acidosis - low pH Stimulates hyperventilation Alkalosis - high pH Suppresses ventilation
31
What organ besides brain contributes to long term pH regulation, how?
Kidneys Help buffer blood pH by producing and excreting bicarbonate ions
32
What is the hypoxic ventilatory response and role of carotid bodies?
HVR is increased breathing triggered by low oxygen levels Detect decreased O2 levels Signal to nervous system Result in hyperventilation
33
What is the role of pulmonary smooth muscle cells in hyopxia?
Constrict vessel in response to local low O2 Optimise ventilation perfusion matching
34
How does the strength of HVR compare to CO2 driven ventilation control?
HVR weaker than CO2/pH driven response mediated by central chemoreceptors Acts as an additional compensatory mechanism when required
35
What causes respiratory alkalosis during acute hypoxia?
Hyperventilation results in decreased CO2 - Increases blood pH - Further suppresses breathing via central chemoreceptors
36
How is respiratory alkalosis pohsyiologically mitigated?
Kidneys Production of bicarbonate ions as buffer
37
How is overcompensation avoided?
Acute response to hypobaric hypoxia is disrupted by regulatory response to hypercapnia Ensures balance of O2 and CO2 levels in regulating breathing
38
Explain ventilatory acclimatisation to hyopxia?
Increased sensitivity of carotid bodies - Allowing more efficient detection of hypoxic conditions Sustained increase in breathing - Maintain oxygen intake in low oxygen environment
39
How does acclimatisation improve oxygen delivery during hypoxia?
Angiogenesis - Growth of blood vessels - Increase capillary network Increased number RBCs - Stimulation of erythopoiesis - Increase oxygen carrying capacity of blood
40
How does acclimatisation result in metabolic changes during hypoxia?
- Increased glycolysis - Decreased aerobic pathways - Protection against oxidative stress
41
How does HIF oxygen sensing system work in very low O2?
1. HIFa moves to nucleus in functional state 2. Interacts with proteins in complex 3. Binds to hypoxia response elements (HRE) 4. Strongly stimulates transcription of genes that assist in coping with low O2 levels eg. carotid body sensitivity, increased synthesis RBCs
42
What is the role of PHD and VHL in normoxia?
PHD (proline hydroxylase domain) Uses O2 as substrate and hydroxylates HIFa VHL After PHD, VHL can ubiquitinate HIFa Target for degradation
43
What is the role of FIH1 in oxygen sensing?
FIH1 (factor inhibiting HIFa) uses O2 as substrate - Also hydroxylates HIFa but at different position - HIFa may enter nucleus but interactions are blocked - Prevents transcription activation
44
How does the oxygen sensing system work in normoxia?
HIFa continuously expressed and mostly degraded Remaining HIFa cannot activate transcription for hypoxia-responsive genes
45
How does HIF oxygen sensing system work in low O2?
High Km of PHD - Low affinity - Requires higher O2 levels - Some accumulation Low Km of FIH1 - Higher affinity - Continues hydroxylation acivity - Some HIFa still able to stimulate transcription but response decreased
46
Activating transcription by HIFa upregulates what genes?
Increased sensitivity of carotid bodies Promoted erythropoiesis
47
What are two conditions caused by poor acclimatisation?
Chronic mountain sickness Pulmonary hypertension
48
Symptoms of chronic mountain sickness (CMS)?
Erythrocytosis Sleep disturbance (periodic breathing) Cyanosis Increased stroke risk
49
Symptoms of pulmonary hypertension
Persistent vasoconstriction Decreased diameter/elasticity Disrupts O2 transport Right ventricular failure
50
Compare chronic mountain sickness and pulmonary hypertension?
Some overlap with similar symptoms Different causes CMS caused by excessive RBC production - Slows blood flow PH caused by persistent pulmonary vasoconstriction - Artery remodelling
51
What are the causes of CMS and PH?
Genetic variability in susceptibility Seen in long-term high altitude sojouners, less in indigenous Less ventilatory acclimatisation to hypoxia, increased activity of other hypoxic responses - chronic pulmonary vasoconstriction -> remodelling - chronic increases in erythrocyte formation -> viscosity of blood
52
What are the evolutionary adaptations in high altitude mammals?
Sustainable, helpful responses to hypobaric hypoxia - Maintain consistent hyperventilation - Increased levels of lactate - Typically don't have increased RBC concentration
53
What kinds of mutations are common in HIF system of high altitude mammals?
High alt mammals often show loss of function of HIF systems - Blunt or reduce response to hypoxia
54
Why are mutations that reduce sensitivity to hypoxia advantageous to high altitude mammals?
Help avoid excessive responses Enables mores stable metabolic adaptation to chronic hypoxia
55
What are the effects of PHD2 mutations that affect translation and folding in high altitude mammals?
Loss at translation - Increased erythrocytosis Loss at folding - Increased hypoxic ventilatory response
56
What is the significance of the D4E/C127S Tibetan allele?
Increases oxygen affinity - Function at lower oxygen levels Decreases binding to chaperone p23, modifying HIF system activity Modulate degradation of HIFa and blunt hypoxic response
57
Why are other physiological adaptations in high altitude mammals?
- Altered haemoglobin affinity - Increased capillary density - Smaller RBCs