Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Digestion And Metabolism > Digestion And Metabolism > Flashcards

Digestion And Metabolism Flashcards

1
Q

How is ATP changed by oxidative phosphorylation?

A
  • Carbohydrates, fatty acids and amino acids are oxidized to CO2 & H2O
  • Intermediates of the reactions donate electrons to form REDUCED energy rich molecules, coenzymes NADH, FADH2
  • NADH and FADH2 each donate a pair electrons to electron carriers of the Electron Transport Chain (ETC)
  • As electrons are passed down the ETC, they lose free energy
  • This energy is used to move protons across the inner mitochondrial membrane and create a H+ gradient
  • The H+ gradient drives oxidative phosphorylation: ATP synthesis
  • The movement of electrons through the ETC ultimately leads to the phosphorylation of ADP to ATP “Oxidative Phosphorylation”
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Explain the structure function off the mitochondria

A
  • Mitochondria – double membrane organelles
  • energy powerhouses
  • Centre termed the matrix – TCA Cycle enzymes
  • Outer membrane is permeable to most molecules
  • Inner membrane highly impermeable and highly
  • folded into invaginations - cristae
  • Enzymes of the ETC and ATP synthase found on the Inner membrane.
  • Inner membrane cristae increase membrane surface area and its impermeability allows the establishment of chemical gradients
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is the ETC & OxPhos function?

A

• Oxidize NADH and FADH2
2

  • Generate electrical energy by passing electrons to Oxygen H+
  • Create a proton gradient across inner mitochondrial membrane
  • Proton gradient drives phosphorylation of ADP to ATP
  • 2 stages
  • Electron transport then Oxidative phosphorylation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is the significance of NADH dehydrogenase?

A

Complex 1

  • Will oxidize NADH & reduce Coenzyme Q (CoQ)
  • Tightly bound riboflavin-5’-phosphate prosthetic group (FMN) derived from B2 (riboflavin) which reversibly accepts and releases electrons
  • Contains iron-sulfur clusters, covalently attached to cysteine residues, which reversibly accepts and releases electrons
  • NADH electrons from TCA and PDH, FAO & glycolysis
  • Movement of electrons shown in magenta, from NADH to CoQ
  • This energy is used to pump 4 protons across the inner-mitochondrial membrane to the intermembrane space
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is the function of complex 2: Succinate-Q-Reductase?

A
  • Succinate dehydrogenase (TCA Cycle)
  • Will oxidize succinate and reduce CoQ
  • Electrons come from succinate and FAO or glycerol phosphate shuttle (generating FADH2)
  • Tightly bound FAD prosthetic group derived from B2 (riboflavin) and adenine
  • Contains iron-sulfur clusters
  • Contains binding site for succinate and CoQ
  • Flow of electrons are shown in magenta
  • Does not span the membrane like Complex 1
  • No protons are translocate
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is the function of Complex III- Cytochrome b-c1 complex?

A
  • Will oxidize CoQ and reduce Cyt c
  • Spans the membrane
  • Movement of electrons shown in magenta, from CoQ to Cyt c
    • This energy is used to pump 4 protons across the inner-mitochondrial membrane to the intermembrane space
  • Flow of electrons shown in green will regenerate CoQ
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is the function of complex IV?g

A

Complex 4: cytochrome c oxidase

  • Oxidized cytochrome c and reduces oxygen to water
  • O2 is the final electron acceptor
  • Spans the membrane
  • Contains two heme groups which are each positioned close to a bound copper atom (binuclear centers)
  • Movement of electrons shown in magenta, from Cyt c to oxygen
  • This energy is used to pump 2 protons across the inner-mitochondrial membrane to the intermembrane space
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are the mobile electron carriers?

A

• Coenzyme Q or Ubiquinone or Q10 so called because of
ubiquitous “expression” and the presence of its
10-isoprenoid residue hydrophobic tail
• Non-protein lipid soluble molecule
• Can accept 2 electrons from donors and release a single electron to
acceptors

• Cytochrome c: small heme protein bound to the
intermembrane space side of the inner membrane
• Heme group is Heme c which is covalently linked to the protein
• Acts as an electron shuttle between Complex III & IV

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is the structure function of ATP synthase?

A

• Multi-subunit enzyme: F0 and F1 portions

• F0 in the inner mitochondrial matrix contains the
proton pore

  • F1 in the mitochondrial matrix contains the catalytic activity (ATP synthesis)
  • Protons that have been pumped to the cytoplasmic side of the IMM re-enter the matrix through an H+ channel in the F0 domain of ATP Synthase
  • This drives rotation of the C ring which then drives ATP synthesis
  • One complete rotation of C ring uses 8 protons and produces 3 ATP
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is the P/O ratio?

A
  • Complex I and III pump 4 H+ & Complex IV pumps 2 H+ into intermembrane space
  • ~3-4 H+ required to synthesize 1 ATP
  •  NADH entering at Complex I pumps 10 H+ = 2.5 - 3 ATP
  •  FADH2 entering at Complex II pumps 6 H+ = 1.5 - 2 ATP
  • P/O ratio is a measure of the number of high-energy phosphate bonds synthesized per atom of oxygen consumed i.e. The number of ATP per 1⁄2 O2
  • P/O ratio for NADH = ~3
  • P/O ratio for FADH2 = ~2
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

How much ATP is generated per molecule of glucose?

A

Glycolysus- substrate Level phosphorylation - 2 ATP
2 NADH generation- 4 or 6 ATP

Puruvate dehydrogenase- 2 NADH- 6 ATP

Citric acid-
Substrate level phosphorylation- 2 ATP
6 NADH- 18 ATP
2 FADH2- 4 ATP

TOTAL= 36 or 38 ATP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is the purpose of NADH?

A
  • NADH cannot cross the Inner mitochondrial membrane
  • Shuttle is required to deliver NADH electrons from cytosol (glycolysis) to the mitochondrial matrix
  • FADH2 will donate electrons to CoQ
  • NADH will donate electrons to Complex I, regenerating NAD+
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Explain oxidative phosphorylation & the Chemiosmotic theory

A

Proton motive force

Mitchell’s Chemiosmotic Theory: 2 steps
Step 1
• As electrons flow down electrochemical potential, protons are pumped into the intramembrane space
• Protons are pumped into intramembrane space at complexes I, III & IV
• Protons cannot re-enter the matrix alone

Step 2
• This creates a pH gradient that is relieved by pumping protons back thru F0F1-ATP synthase (Complex V). The energy released in this process is coupled to ATP synthesis from ADP and Pi.
• pH different across the inner membrane ~0.75 pH units

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are the inhibitors ofETC ?

A

Decrease in ATP synthesis, ETC activity & oxygen consumption

Inhibitirs of complex I
Amytal: barbiturate 
Rotenone: insecticide 
Piericidin A: bacterial antibiotic 
Does not affect flow from complex II-

Complex III-cytochrome reductase inhibiitirs

Antimycin A: antibiotic Inhibits cyt b

Conplex IV inhibitors

Cyanide: CN- 
Azide: NaN3
Hydrogen sulfide: H2S 
Carbon monoxide: CO
All inhibit heme a3-Cu

Complex V ATP synthase

Oligomycin: antibiotic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are the inhibitors of ETC complexes I, III & IV?

A

• Will reduce electron transport and establishment of a proton gradient

• ATP synthesis depends on the proton gradient, thus a reduction in electron
transport results in a reduction of ATP synthesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What are the inhibitirs of ATP synthase?

A
  • Electron transport is initially unaffected, and establishment of a proton gradient will occur
  • Once a maximum gradient has been established, the electron flow will be inhibited
  • Protons can leak back into the matrix by facilitated diffusion of the protons with “uncoupling proteins” like thermogenin
  • This “uncouples” the activity ETC from ATP synthase
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q
  1. How does the ATP move from the mitochondrial matrix into the cytosol?
  2. How does the ADP and move from the cytosol to the mitochondrial matrix to be used as substrate for
    ATP Synthase?
A
  1. ATP and ADP transported via an Antiport – 1:1 exchange, ATP out, ADP in
  2. Driven by the electrochemical gradient and membrane potential
  3. Pi is transported together with a H+ symport not shown
18
Q

What is the function of Adenine nucleotide translocase?

A 
• Adenine nucleotide translocase (ANT): unidirectional exchange of ATP
for ADP (antiport)

• Symport of Pi and H+ is electroneutral

19
Q

What is atractyloside?

A

Atractyloside; toxic glycoside (molecule with a sugar and a noncarbohydrate element) from thistle plant Atractylis gummifera

• Binds the outward facing (inter-membrane space) portion of the adenine nucleotide transporter

20
Q

What is Bongkrekic acid?

A

respiratory toxin produced in coconuts contaminated with Burkholderia gladioli

• Binds the inward facing (matrix) portion of the adenine nucleotide transporter

21
Q

What are the effects of Atractyloside and Bongkrekic acid?

A

Effect of both are similar to oligomycin
Complex V can’t dissipate proton gradient if inhibited or has no substrate

ETC will shut down as well, failure to dissipate proton gradient

22
Q

What is the final aacceptor of electrons?

A

Oxygen

23
Q

What happens in ETC in hypoxia?

A
  • Hypoxia decreases the rate of ETC and ATP production.
  • A drop in cellular ATP increases anaerobic glycolysis and lactic acid production, anaerobic glycolysis cannot meet most tissue demands (neural tissue, cardiac muscle).
  • Myocardial infarction can result from hypoxia, leading to tissue damage, leakage of intracellular enzymes (CK1, CK2, LDH) and troponin I and T.
24
Q

Explain uncoupling of oxidative phosphorylation

A

• Uncoupling occurs when H+ re-enter the mitochondrial matrix without going through ATP synthase

  • “Dissipation” of the proton gradient results in:
    • Reduction in ATP synthesis
    • Increase activity in all complexes of ETC activity (not slowed down by proton gradient)
    • Increase in Oxygen consumption (Complex IV activity is increased)
    • Release of energy as heat
  • Proteins and synthetic uncouplers
25
Q

What are the uncouplers of oxidative phosphorylation?

A

Uncouplers destroy the proton gradient:
Synthetic uncouplers:
• DNP (2,4-dinitrophenol)
• ASA (aspirin)

Ionophores
• Gramicidin (channel forming ionophore)
• Valinomycin (mobile carrier)

Uncoupling proteins:
• UCP1 - thermogenin,

Uncouplers:
decrease ATP synthesis, increase ETC and Oxygen consumption

26
Q

What are synthetic uncouplers?

A

• Chemical uncouplers, also termed proton ionophores, lipid soluble act
by destroying the proton gradient

  • DNP (2,4-Dinitrophenol)
  • ASA (aspirin)
27
Q

What is the mechanism of action of Valinomycin?

A

Mobile ionophore

• Antibiotic from Streptomyces strains

  • Makes inner membrane permeable to potassium ions,
    • carries K+ across bilayer
  • Polar inside for K+ and non-polar lipophilic outside
  • pH gradient still intact but dissipates the membrane potential
28
Q

What is the mechanism of action of Gramidicin?

A

• A mixture of 6 peptides produced by Bacillus brevis which form helices that span lipid bilayers, most often head-to-head dimers of gramicidin A

• Channel forming ionophore makes a pore through the IMM and makes it
permeable to H+

29
Q

What is the significance of uncoupler proteins?

A
  • Physiological uncoupling of oxidative phosphorylation involves uncoupling proteins (UCPs)
  • UPCs form channels through the inner membrane which conduct H+ back into the matrix (leaky membranes)
  • When UCPs are activated, dissipation of the H+ gradient generated from electron transport is uncoupled from ATP synthesis, generates heat
30
Q

What is the significance of UCP1-Thermogenin?

A
  • Thermogenin (UCP1) is expressed in brown adipose tissue
  • Generation of heat is the physiological function of brown adipose tissue
  • “non shivering” thermogenesis
31
Q

What is thermogenin?

A
  • Hormone induced release of fatty acids from triglycerides in brown fat leads to activation of thermogenin
  • Thermogenin is brown because of the abundance of cytochrome-containing mitochondria
  • Newborns have brown fat in neck and upper back, acts as biological heating pad
  • ‘Non-shivering thermogenesis’
32
Q

How do mitochondrial mutations affect OxPhos?

A

• mtDNA for 13 subunits of respiration complexes (pink), 2 rRNA (blue) and 22 tRNA (black)

• Common mitochondrial mutations known to result in disease are shown (FYI and not on a test)
• Mutations in subunits of the complexes cause
disease

  • CO=Cytochrome Oxidase
  • ND=NADH dehydrogenase
  • Cyt b=Complex III
  • Affects tissues with high energy demands:
  • Muscle weakness
  • Vision and/or hearing problems
  • Heart/liver/kidney problems
  • Learning disabilities
33
Q

What are the hereditary mitochondrial diseases?

A

Leber’s Hereditary Optic Neuropathy
Defect in Complex I

Deafness induced by aminoglycoside antibiotics (rRNA)

Mitochondrial myopathies (disease of the muscle):

34
Q

What are the mitochondrial myopathies (disease of the muscle)?

A

Kearns-Sayre syndrome (deletion in mtDNA)

MELAS Syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes)

MERRF syndrome (myoclonic epilepsy; ragged red fibers)

35
Q

What are the characteristics of Leber’s hereditary Optic Neuropathy?

A

Characterized by degeneration of the retinal ganglion cells (RGCs) and atrophy of the optic nerve

Most common cause of optic atrophy

  • Usually begins between the ages of 25 and 35 (but can occur at any age) and leads to legal blindness
  • Critical threshold (90%) in proportion of mutations in mtDNA must be exceeded before disease appears
36
Q

How can deafness be induced by aminoglycoside?

A
  • Mitochondrial hearing loss is characterized by moderate to profound hearing loss
  • Maternally inherited mutation most commonly in mitochondrially encoded rRNA
  • Mutation may cause predisposition to aminoglycoside toxicity causing deafness and/or late onset
  • Hearing loss occurs within a few days to weeks after administration of any amount of aminoglycoside antibiotic.
  • An individual with many mitochondria containing mutations may have childhood onset of hearing loss
37
Q

Explain Kearns-Sayer

A

• Deletion within mitochondrial DNA

  • Most common region is 4997 bp
  • Affects systems with higher energy requirements
  • Onset before 20 and includes:
  • Paralysis of eye muscles and degeneration of retina
  • Cardiac problems or congestive heart failure
  • Muscle and skeletal weakness
  • Ataxia (coordination problems)
  • Diabetes, dementia and other mental illnesse
38
Q

What are the characteristics of MELAS?

A

Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis, and Stroke-like episodes
• It is the most common mitochondrial disease

• Clinical Features: Strokes, myopathy (weak muscles), muscle twitching,
dementia, and deafness

  • Presentation occurs with the first stroke-like episode at 14-15 yrs of age
  • Most commonly due to mutation in mitochondrial tRNA
  • Lactic acid accumulates in blood and is toxic to the brain
39
Q

What are the symptoms of MERRF?

A
  • Myoclonic Epilepsy; Ragged Red Fibers
  • Most common mutation in mitochondrial tRNA gene

• Symptoms of MERRF typically begin in age 6-16 years old

• Myoclonus is usually the first symptom followed by:
– Seizures, ataxia, muscle weakness, worsening eye sight and hearing loss

40
Q

Explain the causes of ragged red fibers

A
  • Defective mitochondria have mutations in mtDNA or genes on nuclear DNA targeted to mitochondria
  • Low amount of energy production

• The cell tries to survive low energy status by
proliferating (multiplying) the mitochondria

• Defective mitochondria proliferate and accumulate
in the specific regions of muscle

• Appearing as “Ragged Red Fibers” when muscle is
stained with Gomoritrichrome stain as shown to the right

41
Q

How can mitochondrial proliferation in muscle fibers be observed?

A

By staining for oneof the complex of oxidative phosphorylation

Digestion And Metabolism (57 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions