Module 10 - Cellular Respiration

included on exam 3

glycolysis

the splitting of glucose into two pyruvates

occurs in the cytoplasm (all reactions)

3 phases: energy investment, 6C→3c sugar cleavage, energy generation (payoff)

the 3 phases of glycolysis

investment: steps 1-3

cleavage: steps 4-5

payoff: steps 6-10

steps 1-3 of glycolysis (investment phase) explained

1) phosphorylation:

glucose + ATP → glucose 6-phosphate (G6P) + ADP + H⁺

enzyme: hexokinase

irreversible

2) isomerization:

G6P → fructose 6-phosphate (F6P)

enzyme: phosphoglucose isomerase

reversible

3) phosphorylation:

F6P + ATP → fructose 1,6-bisphosphate (F1,6-BP) + ADP + H⁺

enzyme: phosphofructokinase

irreversible

all molecules in this step have 6 carbons

steps 4-5 of glycolysis (cleavage phase) explained

4) cleavage:

F1,6-BP → glyceraldehyde 3-phosphate (G3P) and dehydroxyacetone phosphate (DHAP)

enzyme: aldolase

reversible

note for step 4: G3P and DHAP both have 3 carbons

5) isomerization:

DHAP → G3P

enzyme: triose phosphate isomerase

reversible

note: at the end of the cleavage phase, 1 F1,6-BP has become 2 G3P

steps 6-10 of glycolysis (payoff phase) explained

6) oxidation (x2):

G3P+ NAD⁺ + P_i → 1,3-bisphosphoglycerate (1,3-BPG) + NADH + H⁺

(2 NAD+ are reduced to 2NADH, and a P_i (inorganic phosphate) is attached to each C1)

enzyme: G3P dehydrogenase

reversible

7) ATP synthesis by substrate-level phosphorylation (x2):

1,3-BPG + ADP → 3-phosphoglycerate (3PG) + ATP

transfer of 1P from BPG to ADP

enzyme: phosphoglycerate kinase

reversible

8) isomerization (x2):

3PG → 2-phosphoglycerate (2PG)

enzyme: phosphoglycerate mutase

reversible

9) dehydration (x2):

2PG into phosphoenolpyruvate (PEP)

2H2O are removed

enzyme: enolase

reversible

10) ATP synthesis by substrate-level phosphorylation (x2):

PEP + ADP + H⁺ → pyruvate + ATP

transfer of 1P from PEP to ADP

enzyme: pyruvate kinase

irreversible

all steps in this phase are repeated twice, because of the 2 G3P yielded in the cleavage phase

yield of glycolysis

2 ATP consumed during energy investment phase

4 ATP and 2 NADH produced during payoff phase

net yield: 2ATP + 2 NADH

glycolysis under anaerobic conditions

pyruvate and NADH (some products of glycolysis) are consumed in fermentation

NAD⁺ is regenerated and reused in step 6 of glycolysis (oxidation of G3P)

3 types of muscle fibers

slow

fast

intermediate

slow muscle fibers

muscle fibers that generate ATP in mitochondria by oxidative phosphorylation

have high density of myoglobin → appear dark red

myoglobin

the oxygen-carrying protein in the muscles of most mammals

very dense in slow muscle fibers

fast muscle fibers

muscle fibers that generate most of their ATP by fermentation (anaerobic respiration)

appear white because of lack of myoglobin

intermediate muscle fibers

muscle fibers that generate some ATP by oxidative phosphorylation and some by fermentation

appear lighter red because of moderate density of myoglobin

fermentation (aka anaerobic respiration)

reduction of pyruvate in the absence of oxygen

NADH gets oxidized to NAD⁺

occurs in the absence of oxygen

driven by the oxidation of NADH generated from glycolysis

end products are excreted

net yield: 2 ATP (from glycolysis)

fermentation in white muscle fibers

pyruvate is reduced to lactic acid

NADH is oxidized to NAD⁺

(lactate gets excreted)

fermentation in oxygen-deprived yeasts

pyruvate is hydrolyzed to acetaldehyde

acetaldehyde is reduced to ethanol

note: acetaldehyde and ethanol have 2 carbons, not 3 like pyruvate

CO2 is produced during hydrolysis

NADH is oxidized to NAD⁺ during reduction

(ethanol and CO2 get excreted)

aerobic respiration

occurs in aerobic conditions, following glycolysis

pyruvate and NADH go to the mitochondria

pyruvate reacts with coenzyme A → converted into acetyl CoA, enters the citric acid cycle

NADH powers oxidative phosphorylation reactions (electron transport chain)

mitochondrion (plural mitochondria)

the membrane-closed organelle that generates most of the cell’s supply of ATP

found in most eukaryotic cells

necessary for earobic respiration

consists of matrix, inner membrane, and cristae with intermembrane space

site of citric acid cycle, electron transport chain, and oxidative phosphorylation

matrix

the site of oxidation of pyruvate and the citric acid cycle, in mitochondria

inner membrane of mitochondria

site of the electron transport chain and oxidative phosphorylation, in mitochondria

cristae

infoldings of the inner membrane of the mitochondria

contain intermembrane space inside

oxidation of pyruvate

pyruvate + CoA-SH → acetyl CoA + CO2

occurs in the mitochondrial matrix

1 NAD⁺ is reduced to NADH + H⁺

acetyl CoA

a 2-carbon product of the oxidation of pyruvate

contains a thieoster bond that releases a large amount of energy when hydrolyzed

the 2 carbons are derived from glucose

citric acid cycle (CAC), aka Kreb’s cycle, aka TCA cycle

the production of several NADHs, FADH₂, and GTP from acetyl CoA

steps of the citric acid cycle

1) condensation:

acetyl CoA (2C) + oxaloacetate (4C) → citric acid (aka citrate) (6C)

driven by the hydrolysis that removes CoA

2) isomerization:

citric acid (6C) → isocitrate (6C)

3) oxidation of isocitrate:

isocitrate (6C) → alpha-ketoglutarate (alpha-KG) (5C)

CO2 produced, NAD⁺ reduced to NADH

4) oxidation of alpha-KG:

alpha-KG (5C) → succinyl CoA (4C)

CO produced, NAD⁺ reduced to NADH

CoA-SH added back

5) hydrolysis:

succinyl CoA (4C) → succinate (4C)

CoA-SH removed, GTP synthesized and hydrolyzed to GDP, ATP synthesized

6) oxidation of succinate:

succinate (4C) → fumarate (4C)

FAD reduced to FADH₂

7) hydrogenation:

fumarate (4C) → malate (4C)

H₂O consumed

8) oxidation of malate:

malate (4C) → oxaloacetate (4C)

NAD⁺ reduced to NADH

oxaloacetate and a new acetyl CoA restarts the cycle

yield of the CAC

3 NADH, 1 FADH₂, 1 ATP per turn

2 pyruvates are used, so 2 turns:

total: 6 NADH, 2 FADH₂, 2 ATP

NADHs and FADH₂s go to the electron transport chain (high-energy electrons get donated after being released by oxidation)

oxidative phosphorylation: the ETC

occurs in the mitochondria, after the CAC

H⁺s get pumped from the matrix into the intermembrane space (by respiratory enzyme complexes in the inner membrane, containing electron-carrying cofactors)

H⁺ pumping is driven by the energy of the electrons from NADH and FADH₂ (oxidation) → generates a H⁺ gradient across the inner membrane

flow of H⁺ back into the matrix powers ATP synthesis

electrons lose energy

oxygen is the final electron acceptor: ½O₂ + 2H⁺ → H₂O

ETC complexes

I: NADH dehydrogenase complex (accepts electrons from FADH₂) (NADH → NAD⁺)

Q: ubiquinone (coenzyme Q₁₀)

II (FADH₂ → FAD)

III: cytochrome b-c₁ complex

IV: cotychrome oxidase complex (produces ½O₂ + 2H⁺ → H₂O)

ATP synthase (technically separate from the complexes)

ATP synthase complex

where ATP is synthesized in the ETC

powered by the H⁺ gradient generated by the ETC

H⁺s flow back into matrix → central unit of the complex rotates → ATP synthesis is powered

result: oxidative phosphorylation of ATP → ATP

(result of oxidation of all the electron carriers)

yield of aerobic respiration, per 1 glucose molecule

from glycolysis and CAC: 4 ATP

from oxidative phosphorylation:

2 NADHs from glycolysis

2 NADHs from oxidation of pyruvate

6 NADHs from citric acid cycle

2 FADH₂s from CAC

1 NADH → 2.5 ATP → 25 ATP

1 FADH₂ → 1.5 ATP → 3 ATP

4 + 25 + 3 = 32 ATP made

1 ATP spent to transport each NADH from glycolysis to mitochondria → 2 ATP spent

net yield: 30 ATP

metabolism of different foods

proteins → amino acids

polysaccharides → simple sugars → glucose

fats → fatty acids and glycerol

amino acids, fatty acids, and glycerol get converted into intermediates of aerobic respiration and used to harvest stored energy (e.g. NH₃ and CO₂)

stages of metabolism

1) breakdown of large macromolecules into simple subunits

2) breakdown of simple subunits to acetyl CoA (with production of limited amounts of ATP and NADH)

3) compete oxidation of acetyl CoA to H₂O and CO₂, with production of large amounts of NADH and ATP in mitochondria