A very terse overview of metabolism. Anabolism vs. Catabolism “lysis” i.e., glycolysis “genesis” i.e., gluconeogenesis

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  • Slide 1
  • A very terse overview of metabolism
  • Slide 2
  • Anabolism vs. Catabolism lysis i.e., glycolysis genesis i.e., gluconeogenesis
  • Slide 3
  • Overview of metabolism
  • Slide 4
  • Slide 5
  • The key parts (three high-level views)
  • Slide 6
  • Glycolysis (Chapter 14)
  • Slide 7
  • Glycolysis, cont.
  • Slide 8
  • Three possible fates of pyruvate
  • Slide 9
  • Lower organisms (i.e., yeast) Higher organisms (i.e., mammals) Three possible fates of pyruvate
  • Slide 10
  • Slide 11
  • The traditional, but largely incorrect, view of anaerobic catabolism of glucose First half of glycolysis:-2 ATP Second half of glycolysis:+4 ATP +2 NADH +2 Pyruvate Fermentation:-2 NADH -2 Pyruvate +2 Lactate (or +2 EtOH) Net:+2 ATP + a bunch of other stuff
  • Slide 12
  • Lets take a quick step back Where did the glucose come from to start glycolysis?
  • Slide 13
  • The opposing pathways of glycolysis and gluconeogenesis (note most differences include kinases) Kinase vs. phosphatase: Its not always this simple, but this is typically correct.
  • Slide 14
  • Chapter 16: The Citric Acid Cycle (aka TriCarboxylic Acid Cycle or Krebs Cycle) Citrate
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  • The Citric Acid Cycle
  • Slide 16
  • The TCA cycle involves a series of oxidation reactions that produce a large number of NADH, which -- as you recall -- has accepted a hydride (electrons!) The NADH molecules produced by TCA (and elsewhere) will be used in electron transport to a proton ion gradient (a battery). The potential energy in this battery will be used to drive oxidative phosphorylation, which is the synthesis of ATP (see purple box on previous slide).
  • Slide 17
  • Pyruvate Acetyl-CoA The irreversible commitment to TCA Note: this is technically an oxidation of the pyruvate -carbon (carbonyl to thioester), which is why NADH is produced.
  • Slide 18
  • Pyruvate Acetyl-CoA The irreversible commitment to TCA
  • Slide 19
  • The Citric Acid Cycle
  • Slide 20
  • Note the CO 2
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  • Keeping track up to this point Glycolysis (net):+2 ATP +2 NADH +2 Pyruvate Pyr->Ac-CoA:-2 Pyruvate +2 NADH (1 per pyruvate) +2 Ac-CoA TCA:-2 Ac-CoA +6 NADH (3 per Ac-CoA) +2 GTP (1 per Ac-CoA) +2 FADH 2 (1 per Ac-CoA) +CO 2 and some other carbon bodies Net:+4 ATP (b/c GTP = ATP) +10 NADH +2 FADH 2
  • Slide 22
  • Fatty acid catabolism is called -oxidation (Chapter 17)
  • Slide 23
  • Amino acid catabolism (Chapter 18)
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  • A [H + ] gradient is produced using the free energy produced from electron transport (Chapter 19)
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  • Diffusion and electrochemical gradients
  • Slide 26
  • A [H + ] gradient is produced using the free energy produced from electron transport (Chapter 19) Molecular oxygen is the final electron acceptor
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  • Cytochrome C
  • Slide 28
  • Oxidative phosphorylation using ATP synthase (also Chapter 19)
  • Slide 29
  • How does ATP Synthase work? Experimental demonstration of rotation
  • Slide 30
  • The final score (sorta) Glycolysis (net):+2 ATP +2 NADH +2 Pyruvate Pyr->Ac-CoA:-2 Pyruvate +2 NADH (1 per pyruvate) +2 Ac-CoA TCA:-2 Ac-CoA +6 NADH (3 per Ac-CoA) +2 GTP (1 per Ac-CoA) +2 FADH 2 (1 per Ac-CoA) +CO 2 and some other carbon bodies Net:+4 ATP (b/c GTP = ATP) +10 NADH = +30 ATP (assuming 3 ATP per NADH) +2 FADH 2 = +4 ATP (assuming 2 ATP per FADH 2 ) ----------------------------------------------------------------------- +38 ATP (4 from substrate phosphorylation; 34 from oxidative phosphorylation)
  • Slide 31
  • How come lactate gets such a bad rap?
  • Slide 32
  • Lactate is actually an important fuel The lactate shuttle (middle image). On the left a white muscle fiber producing lactate. This lactate then travels to neighboring muscle tissues ("Ox Fiber") as well as distant tissues like the heart and other muscle cells, where it is used as a fuel. In the middle you see the liver, representing the conversion of lactate to glucose (the Cori Cycle), the traditional view most medical students learn, which is the typical textbook view of lactate (right image). Source: Matthew L. Goodwin, PhD
  • Slide 33
  • Lactate is actually an important fuel (Part of) The Proof. Lactate replacing glucose as a fuel in mammalian hippocampus slices. Two groups of tissues were studied in vitro. In both, glucose was removed from solution (@ first arrow). Both tissues began to fail (spike amplitude falling to 0). In one group nothing was changed after that (closed circles); in the other group (open circles) 10 mM lactate was added at the second arrow. The lactate fully replaced glucose as a fuel and the tissue returned to normal vitality. Source: Matthew L. Goodwin, PhD Restored activity
  • Slide 34
  • Lactate threshold Lactate threshold is actually all about the rate at which your muscles clear lactate from the blood (as it is used as a fuel within other tissues), and not simply an indicator of the point that aerobic metabolism stops. In fact, trained athletes produce AND reuse far more lactate at threshold than untrained people. At LT in both samples above, the blood [lactate] is about the same, but in fact the trained group is producing about 60% more lactate, and thus also clearing it 60% faster. In moderate to well-trained runners, LT is roughly the pace at which he/she can run for one hour.