Catabolism of Glucose and Cellular Respiration

Catabolism of Glucose

  • Approximate yield of ATP from glucose through aerobic oxidation.
  • Enzymes, intermediates, and details can be found at http://www.iubmb-nicholson.org/animaps.html.
  • The process involves glycolysis, pyruvate oxidation, and the citric acid cycle, with the electron transport chain ultimately producing ATP.
  • Malate-aspartate shuttle is used.
  • The diagram shows the flow of electrons and protons, highlighting the complexes involved in the electron transport chain, including NADH dehydrogenase, ubiquinone, cytochrome c reductase, and cytochrome c oxidase.
  • ATP synthase uses the proton gradient to produce ATP.
  • Translocated protons per glucose: The oxidation of 10 NADH and 2 succinate molecules results in the translocation of protons.
  • Less protons are translocated due to the transport of 2 NADH in the shuttle.
  • Retrolocated protons drive the rotation of c-subunits to form ATP.
  • 10 retrolocated protons drive the 10 c-subunits (and γ) one revolution to form 3 ATP.
  • 3 H+ are required for the transport of 3 Pi to form 3 ATP.
  • Total of 13 H+ needed for the formation of 3 ATP.
  • Hence 108 H+ will drive the formation of (108×3)/13=25(108 \times 3) / 13 = 25 ATP.
  • Add 2 ATP formed from GTP in the TCA cycle and 2 ATP formed in glycolysis in the cytoplasm.
  • Approximate total ATP formed per mol of Glucose: 29.
  • Less protons are translocated due to the transport of 2 Pi for formation of GTP in the TCA cycle (-2).
  • Net yield of translocated protons from 1 mol of glucose: 108.
  • Aerobic oxidation of glucose using the malate-aspartate shuttle:
    C<em>6H</em>12O<em>6+6O</em>2+(29ADP+29P<em>i)→6CO</em>2+6H<em>2O+(29ATP+29H</em>2O)C<em>6H</em>{12}O<em>6 + 6O</em>2 + (29ADP + 29P<em>i) \rightarrow 6CO</em>2 + 6H<em>2O + (29ATP + 29H</em>2O)
  • Net gain in glycolysis: 2 ATP.

Objectives

  • Why do you need to eat?
  • Why do you need to breathe?
  • What is glucose, and how is the energy in glucose converted into the energy of ATP?
  • Compare and contrast how cells get cellular energy (ATP) from sugar (glucose) through:
    • Aerobic Respiration
    • Fermentation

Vocabulary

  • Aerobic respiration
  • Alcoholic fermentation
  • Anaerobic
  • ATP synthase
  • Chemiosmosis
  • Citric Acid Cycle (Krebs cycle) (TCA)
  • Electron donors
  • Electron Transport Chain (ETC)
  • Fermentation
  • Final electron acceptor
  • Glycolysis
  • Lactic acid fermentation
  • Mitochondrial matrix
  • NADH and FADH2
  • Oxidative phosphorylation
  • Proton Motive Force
  • Pyruvate
  • Substrate-level phosphorylation

Two Major Ways Organisms Metabolize Sugars and Produce ATP

Aerobic Respiration (Cellular Respiration)

  • Requires oxygen, $O_2$ (“aerobic”).
  • Complete breakdown of sugars to $CO2$ and $H2O$.
  • High energy yield (compared to fermentation).

Fermentation

  • Does not require oxygen $O_2$ (“anaerobic”).
  • Only a partial breakdown of sugars.
  • Low energy yield.

Aerobic Respiration: Nutrition

  • Why do you need to eat?
    • Building blocks, vitamins, minerals.
    • Energy! (Calories)
  • Glucose (cell sugar):
    C<em>6H</em>12O6C<em>6H</em>{12}O_6
  • Glucose Sugar + Oxygen → Carbon Dioxide + Water + energy (ATP)
  • Basic bread recipe includes flour, sugar, salt, water, oil, and yeast.

Aerobic Respiration: Physiological Respiration

  • Why do you need to breathe?
    • Breathe in - Oxygen ($O_2$)
    • Breathe out - Carbon dioxide ($CO_2$)
  • Glucose Sugar + Oxygen → Carbon Dioxide + Water + energy (ATP)

Heart Function

  • Why does your heart beat?
    • To pump food (from your digestive system) and oxygen (from your respiratory system) to cells.
    • Also to remove carbon dioxide.
  • Glucose Sugar + Oxygen → Carbon Dioxide + Water + energy (ATP)

Aerobic Respiration: The General Chemical Reaction

  • C<em>6H</em>12O<em>6+6O</em>2→6CO<em>2+6H</em>2O+energy (ATP)C<em>6H</em>{12}O<em>6 + 6O</em>2 \rightarrow 6CO<em>2 + 6H</em>2O + \text{energy (ATP)}
  • For the reaction, know:
    • Where does $O_2$ go?
    • Where does $CO_2$ come from?
    • How is ATP made?
  • Know this chemical reaction!
  • Energy (ATP):
    • Glucose ~ $1
    • ATP ~ 1 cent
    • 1M glucose = 684 Kcal, 1M ATP = 7.6 Kcal
    • (684/7.6≈90)(684 / 7.6 \approx 90)

Aerobic Respiration: Stages

  • Four stages:
    1. Glycolysis
    2. Pyruvate oxidation
    3. Citric Acid Cycle (Krebs cycle)
    4. Electron transport chain
  • Amount of ATP made in each stage?

What to Know for Stages

  • Where does it happen?
  • What is going in?
  • What is coming out?
  • Where/how/how many energy-carrying molecules are being synthesized?
    • i.e., how many ATPs?
  • Where are electron carriers being made at each stage?
    • i.e., NADH and FADH2

Glycolysis

  • (Glyco = sweet, sugar; lysis = to split)
  • Occurs in the cytosol.
  • Partially metabolizes glucose (6C) into two pyruvate (3C) molecules.
  • No $CO_2$ is released.
  • Does not require oxygen.
  • Net production of 2 ATP.

Glycolysis Location

  • Where? Reactions occur in the cytosol.
  • Plants do have Aerobic Respiration!

Glycolysis Steps

  • Occurs in 10 steps (two halves).
  • First half of glycolysis "activates" and splits glucose into 2 molecules of G3P.
    • Note: requires energy input; 2 ATP used up:
      • Glucose → 2 G3P

Glyceraldhyde-3-Phosphate (G3P)

  • Or PGAL (3-phosphoglyceraldehyde)
  • Or Triose phosphate
  • Recall: glyceraldehyde-3-P
    • 3 carbon sugar
    • Important link in many biochemical pathways.
    • The end product of photosynthesis!

Glycolysis - Second Half

  • Second half of glycolysis extracts energy.
    • G3P -> Pyruvate
    • Note synthesized:
      • 4 ATP
      • 2 NADH
    • ATP made via “substrate-level phosphorylation”
    • $NAD^+$ accepts $e^-$

Glycolysis Summary

  • Where does it happen? Cytosol
  • What is going in? Glucose (6C)
  • What is coming out? 2 Pyruvate 2(3C)
  • Where/how/how many energy-carrying molecules are being synthesized?
    • 2 net ATP
    • 2 NADH
  • Note: No $O2$ used, No $CO2$ made
  • ATP made via substrate-level phosphorylation

Pyruvate

  • What is pyruvate?
    • Nutrition. 2005 Mar;21(3):312-9. Effects of calcium pyruvate supplementation during training on body composition, exercise capacity, and metabolic responses to exercise. Koh-Banerjee PK1, Ferreira MP, Greenwood M, Bowden RG, Cowan PN, Almada AL, Kreider RB.
  • Where are the 3 carbons in pyruvate?
  • Pyruvate still has lots of energy!
  • What happens to the 2 pyruvate?
    • Note: both fermentation and aerobic respiration use glycolysis :)
      • Fermentation
      • Aerobic respiration

Aerobic Respiration (cont.): Pyruvate Oxidation

  • Occurs in the mitochondria.
  • Pyruvate Oxidation: The Reaction
    • Pyruvate + CoA + $NAD^+ \rightarrow$ Acetyl Coenzyme A + $CO_2$ + NADH

Mitochondria Structure/Function

  • Double membrane
  • Citric Acid cycle in the inner compartment (matrix)
  • Electron transport chain proteins are within the inner membrane

Pyruvate Oxidation

  • (Pyruvate -> Acetyl CoA)
  • Recall: 2 pyruvate are made from 1 glucose.
    • Note: 2 pyruvate -> 2 acetyl CoA
      • Released - 2 $CO_2$
      • Produced - 2 NADH

Citric Acid Cycle (TCA Cycle) (Krebs Cycle)

  • Two turns of TCA are needed to complete the metabolism of the original one glucose.
  • Why? Look at all the $NAD^+$ and FAD being reduced.
  • Note: No $O2$ used, Six $CO2$ made

Events in the Matrix (Pyruvate -> Acetyl CoA & TCA) Summary

  • Where does it happen? Mitochondria matrix
  • What is going in? 2 pyruvate 2(3C)
  • What is coming out? 6$CO_2$
  • Where/how/how many energy-carrying molecules are being synthesized?
    • 2 ATP
    • 8 NADH
    • 2 $FADH_2$
  • ATP made via substrate-level phosphorylation.

So Far for One Glucose Molecule

  • Glycolysis gives 2 ATP
  • Citric acid cycle gives 2 ATP
  • Also made are a total of
    • 10 NADH
    • 2 $FADH_2$
    • 2 from glycolysis + 8 from “stage 2 and 3” reactions

Electron Transport Chain

  • (Electron transport phosphorylation or oxidative phosphorylation)
  • Electron donors: NADH and $FADH_2$
  • Final electron acceptor: $O_2$
    • $O2 + 4e^- + 4H^+ \rightarrow 2H2O$
  • Result (Proton Motive Force) - Chemiosmosis: this chemical/charge/pH gradient has potential energy.
  • $H^+$ flow down their concentration gradient through ATP synthase:
    • ADP + Pi → ATP

The Electron Transport Chain

  • Image depicting the electron transport chain and ATP synthase in the inner mitochondrial membrane.

How Arsenic and Cyanide Kill

  • Sites of action for cyanide and arsenic in the electron transport chain.

Summary of Electron Transport Chain

  • NADH & $FADH_2$ are electron donors.
  • $O_2$ is the final electron acceptor.
  • $H_2O$ is the final product.
  • Energy harvested/NADH: approximately 3 ATPs (via Oxidative phosphorylation).
  • Energy harvested/$FADH_2$: approximately 2 ATPs (via Oxidative phosphorylation).

Electron Transport Chain Summary

  • Where does it happen? Mitochondria, inner membrane
  • What is going in? electron donors (NADH & $FADH2$), electron acceptor ($O2$)
  • What is coming out? $NAD^+$ & FAD, $H_2O$
  • Where/how/how many energy-carrying molecules are being synthesized?
    • Lots of ATP (28 - 34)
    • via oxidative phosphorylation

Maximum ATP Output

  • Glycolysis: 2 ATP
  • Pyruvate oxidation: 2 NADH -> 6 ATP (Chemiosmosis)
  • Krebs Cycle: 2 ATP + 6 NADH -> 18 ATP (Chemiosmosis) + 2 $FADH_2$ -> 4 ATP
  • Total net ATP yield = 38 (36 in eukaryotes)
  • Efficacy? Do the math. Maximum 7.6×38=2897.6 \times 38 = 289, so 289684≈42%\frac{289}{684} \approx 42\%.

Alternative Fuel

  • Can cells use proteins & lipids to produce energy (ATP)?
    • Macromolecules' building blocks feed into various parts of the above reactions.
    • Big reason why you need to pee.

Reversal of Reactions

  • These reactions also work in reverse to make amino acids and fatty acids (the building blocks of your proteins and lipids).

Fermentation Context

  • What happens to the 2 pyruvate from glycolysis?
    • Note: both fermentation and aerobic respiration use glycolysis :)
      • Fermentation
      • Aerobic respiration

Fermentation Definition

  • Does not require oxygen (anaerobic).
  • Only a partial degradation of sugars.
  • Low energy yield - only 2 ATP.

Fermentation - 2 Parts

  • Two parts:
    • Glycolysis plus a way to
    • Regenerate $NAD^+$
      • Recall for glycolysis: Only a total of 2 ATP produced per glucose.
      • $NAD^+$ accepts $e^-$

Regeneration of NAD+

  • Why must $NAD^+$ be regenerated?
  • Two major ways to regenerate $NAD^+$
    • i.e., Two main types of fermentations:
      1. Alcoholic fermentation
      2. Lactic acid fermentation

Alcoholic Fermentation

  • Pyruvate → ethanol and carbon dioxide
  • Ex. yeast (used in the production of baked goods & alcoholic beverages)
  • C<em>6H</em>12O<em>6→2CO</em>2+2C<em>2H</em>5OH+2ATPC<em>6H</em>{12}O<em>6 \rightarrow 2CO</em>2 + 2C<em>2H</em>5OH + 2ATP

Lactic Acid Fermentation

  • Pyruvate → lactic acid
  • Examples:
    • Certain bacteria (ex. Those used in the production of cheese & yogurt, kimchi, sauerkraut, etc.)
    • Human muscle cells in oxygen debt
    • C<em>6H</em>12O<em>6→2C</em>3H<em>6O</em>3+2ATPC<em>6H</em>{12}O<em>6 \rightarrow 2C</em>3H<em>6O</em>3 + 2ATP
  • Why do your muscles hurt after doing exercise?

What to Know for Fermentation

  • Where does it happen? Cytosol
  • What is going in? Glucose -> 2 pyruvate
  • What is coming out?
    • Ethanol + $CO_2$ OR
    • Lactic acid
  • Where/how/how many energy-carrying molecules are being synthesized?
    • 2 ATP via substrate-level phosphorylation
    • $NAD^+$ regenerated

Fermentation Advantage

  • If fermentation gives such a small energy payoff, why are there organisms that use it?
  • What environments would favor fermentation?
    • “Dirty” compost pile

Dead Zones