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Respiration - Coggle Diagram

- - - - inhibited by its reaction product, glucose 6-phosphate (which blocks the active site)
      - its isoforms bind to and are active on cytoplasmic surface of mitochondria outer membrane to coordinate glycolytic system and mitochondrial activity
      - some isoforms can enter the nucleus and act as cofactors for Tfs to control energy metabolism by regulating enzyme synthesis
    - - is negatively controlled by ATP, citrate (derived from pyruvate) and protons
      - positively controlled by AMP and fructose 2,6 bisphosphate
      - AMP and ADP control enzyme and bind to allosteric site, so the enzyme is activated as the energy charge (which is a measure of fraction of total adenosine phosphates that have high energy) of the cell falls
      - addition of fructose-2,6 bisphosphate prevents ATP binding, it is formed from fructose-6-phosphate catalysed by phosphofructokinase-2 and reversed by F-2,6 BP phosphatase. High abundance of fructose 6-phosphate accelerates its subsequent metabolism under feed-forward activation, which activates phosphofructokinase-1
      - ATP binding inhibits but is also a substrate for the enzyme, but the affinity for substrate-binding is much higher (lower Km) than allosteric site, so at low ATP concentrations it binds to catalytic site and at high concentrations it also binds to allosteric site
    - - negatively controlled by ATP (since lots means enough respiration has occured) and alanine (this prevents glycolysis taking priority of other biosynthesis processes)
      - positively controlled by fructose 1-6 bisphosphate (stops process from backing up)
  - - - during prolonged mammalian skeletal muscle cells oxygen can become scarce and glucose catabolism limited to glycolysis
      - muscles convert 2 pyruvates to 2 lactic acid by reduction, which oxidises 2 NADH to 2 NAD+
      - a monocarboxylic transporter transports lactate out the cell which passes to the liver where it is reoxidised to pyruvate in the cori cycle
      - if too much lactic acid accumulates it can cause decrease in pH
- - - - found facing into a compartment at a lower pH
      - is a transmembrane complex containing amphipathic helical subunits (between 10 and 14)
      - positive P-phase due to higher H+ concentration
      - has a transmembrane subunit bound to the outside of the ring which contains the proton channel (2 proton half channels) and 2 stalk subunits projecting into the matric and holds the F1 b subunit
      - contains 3 types of integral proteins (a,b,c)
    - - is always in compartment corresponding to cytosol
      - negative N-phase (matrix)
      - water soluble globular complex that contains 3 pairs of subunits and a central stalk of a 3 sided axle subunit
  - - - the F1 was isolated and attached covalently to glass cover and an actin filament
      - the F1 hydrolyses ATP and actin rotates
      - found shorter actin have faster spin, low ATP concentrations have slow speed (because of Michaelis Menton kinetics) and actin takes 120 degree jumps because of 3 alpha-beta pair subunits
    - - rotation is driven by protonation of aspartate side chains in c subunit
      - the ionization of carboxylic acid group in Asp61 (since proton attracted to negative charge) and charged isoform is hydrophillic so does not move in membrane
      - addition of a proton from the intermembrane space occurs via half channel I (in a subunit of F0) which allows c subunit of F0 facing the proton half channels to move in membrane causing rotation
      - the rotation moves the negative Asp side chain near the half channel of a subunit and moves protonated Asp near the exit site
      - the protons exits via half channel II and enters N-phase and negative Asp attracts proton
  - - - exchanges ATP and ATP in 1:1 ratio
      - binding of ADP brings conformational change
      - make up 10-15% of proteins in inner membrane
    - - the hydroxide combines with a protein in intermembranal space to form water
      - exportation is thermodynamically favourable due to high proton number in intermebranal space
      - imports 1 molecule of hydrogen phosphate for 1 hydroxide ion
      - uses 25% of protons pumped out of matrix
- - - - both are bilayers
      - outer membrane has many porins, so very permeable to molecules up to 1000Da (most abundant protein is mitochondrial B-barrel porin called VDAC)
      - the inner membrane has limited permeability but is site of oxidative phosphorylation
    - - they are the numerous invaginations of inner membrane
      - crista junction is the connection between the inner boundary membrane (the flat inner mitochondrial membrane that lies immediately inside and adjacent to the outer membrane) and a crista
      - their length and structures can vary
      - typically form stacks, can be very or less densely stacked
      - MICOS
        
        they are responsible for curvature at crista junctions and mediates close juxtaposition of outer and inner membrane by binding to membrane proteins
        
        they have an integral membrane protein subunit that homo-oligomerises and bends inner membrane
        
        maintains normal crista structure and diffusion barrier to prevent molecule mixing
  - - - inherited cytoplasmically (exclusively maternal) (in mice 99.99% is maternal)
      - they have lost the ability to replicate independently
- - - - pyruvate dehydrogenase
        
        catalyses oxidative decarboxylation of pyruvate
        
        thymine disphosphate is added to pyruvate and produces hydroxylalkythiamine
        
        its activity is increased after influx of calcium into mitochondria
      - dihydrolipoyl transacetylase
        
        disulphide bond is broken and acetyl group removed and attached to long lipoamide to form acetyl lipoamide
        
        acetyl lipoamide is then brought into contact with coA and acetyl group is transferred to coA to form acetyl coA
      - dihydrolipoyl dehydrogenase
        
        regenerates the oxidised form of lipoamide using NADH and FADH
    - - takes place in mitochondria and generates reduced cofactors which produce ATP via oxidative phosphorylation
      - it can take in peroxisomes, but no reduced cofactor is generated and energy is dissipated as heat
      - triglycerides are hydrolysed to glycerol and fatty acids
      - in large amount, fatty acids are toxic so for transport they are reconverted to triglycerides or bound to carriers, hydrolysis of the triglycerides are carried out by lipases regulated by hormones via signal transduction systems
  - - - main function to produce reduced cofactors
      - it is a catabolic route in energy generation
    - - the major anaplerotic reaction is carboxylation of pyruvate
      - phosphoenolpyruvate can be converted to oxaloacetate by carboxylation, catalysed by PEP carboxylase
      - pyruvate can be converted to malate by malic enzyme
      - glutamic acid and aspartic acif can be converted to intermediates by action of transaminases
    - - source of oxygen is not O2 but H2O
      - even though it is not involved in any reaction, its absence means the cycle stops because the mitochondria cannot regenerate NAD+ and FAD substrates
  - - - glyoxylate cycle is a variant of citric acid cycle that generates a 2C compound (glyoxylate) which enables teh cycle to run
      - succinate is exported to mitochondria and used in citric acid cycle
      - they have glyoxylate cycle, which allows them to carry out a net synthesis of carbohydrate from fat
    - - excess glucose is converted to fatty acids then triacylglycerols for storage
      - stage I
        
        fatty acids are converted to a fatty acyl co in cytosol
        
        this is coupled with hydrolysis of ATP to AMP and inorganic pyrophosphate (PPi)
        
        PPi can then be hydrolysed to 2 Pi
        
        the fatty acyl group is covalently transferred to carnitine and moved across inner membrane by acylacnitine transporters
        
        carnitine is released and fatty acyl attaches to another coA
      - stage II
        
        fatty acyl coA is oxidised in a cycle
        
        the carbon atoms are converted to acetyl coA with generation of FADH2 and NADH
        
        these acetyl coA then enter the citric acid cycle
      - perioxisomes
        
        study on mice revealed that they all oxidise fatty acids
        
        perioxisomes oxidise the very lond chains that mitochondria cannot
        
        the organelle lacks ETC, and electrons from FADH2 are immediately transferred to O2 by oxidases to regenerate FAD
        
        NADH produced from perioximal oxidation is exported adn reoxidised in the cytosol
        
        there is no ctric acid cycle so acetyl coA is transported to cytosol and used to synthesise cholesterol
  - - - cytosolic malate dehydrogenase transfers e- from cytosolic NADH to oxaloacetate forming malate and NAD+
      - an antiporter in inner membrane transports malate to matrix in exchange for a-ketoglutarate
      - matrix malate dehydrogenase converts malate to oxaloacetate, reducing NAD+ to NADH
      - oxaloacetate is converted to aspartate (by adding glutamate) which is tehn transported to cytosol in exchange for glutamate
      - a cytosolic transminase converts aspartate to oxaloacetate and a-ketoglutarate to glutamate
- - - - the H+ cannot pass through the membrane and a pH gradient is established
      - Mitochondria molecular pumps act on hydrogen ions which move the protons from the matrix across the inner mitochondrial membrane
      - the electron lost from NADH is picked up by a flavomononucleotide by NADH-CoQ reductase (info on mechanism in textbook)
      - the electron is passed through iron-sulphur complex all with lower redox, each time a little free energy is lost to pump electrons
      - the electrons are eventually picked up by coenzymeQ as it leaves C1, the electrons are picked up by Cu2+ and haem groups and water is eventually made
      - the haem ring in cytochromes consists of alternating double and single bonded atoms, a large number of resonance hybrid forms exists which allow the extra electron delivered to be spread
    - - 2 electrons are grabbed from succinate to form fumarate and are then transferred to FAD then to iron-sulphur
      - succinate is oxidised to fumerate with concomitant reduction of FAD to FADH2, catalysed by succinate dehydrogenase
      - the reduced FADH2 transfers its electrons via a series of redox reactions to coQ
      - the reduced coQ enters the pool of electron carriers in the inner mitochondrial membrane
      - it gives less energy than C1
    - - (same as C1) it completes the reaction 2H+ +O2 + 2NADH <-> 2H2O + 2NAD+
      - the coQ from C1 moves to C3 where the electrons are transferred to an iron-sulphur cluster in the complex and then to cytochrome c1 or bL or bH
      - the 2 electrons are transferred to 2 molecules of oxidised form of cytochrome c
      - Q cycle
        
        2 molecules of CoQH2 are oxidised to CoQ at QO which releases 4 protons in to intermembrane space
        
        at Qi site 1 CoQH2 is regenerated from CoQ and 2 protons (which are derived from CoQH2)
        
        a flexible hinge in the Fe-S containing protein subunit picks up an electron from CoQH2, which causes it to swing to the haem group on cytochrome c1; the second electron cannot now bind to Fe-S, so moves through cytochrome bL and bH (less thermodynamically favourable)
    - - cytochrome c is reoxidised when it transports its electron to cytochrome c oxidase (c4)
      - the first cytochrome c binds to a pair of Cu2+, the next the haem in cytochrome a, next the reduction centre and then cytochrome a3
      - oxygen moves to the reduction centre via one or more hydrophobic channels
      - the 4 electrons meet O2 and form 2 H2O, the intermediates of this (like peroxide anion and hydroxyl radical) are harmful but do not leave the complex
- - - - methanogens use CO2 +4H2 -> CH4 + 2H2O (and cannot survive in oxygen rich environment)
      - nitrogen fixing bacteria use nitrogen to produce CO2 and ammonia (live in symbiotic environment and are anaerobic)
- - - - creatine and phosphate and phosphoenolpyruvate are more favourable than ATP
      - they give so much energy that coupling produces too much waste