Cellular Respiration
1. Glycolysis
2. Oxidation of Pyruvate
3. Krebs Cycle
Glycolysis is only the start
▪ Glycolysis
▪ Pyruvate has more energy to yield
◆ 3 more C to strip off (to oxidize)
◆ if O
2 is available, pyruvate enters mitochondria
◆ enzymes of Krebs cycle complete oxidation of
sugar to CO2
2x
6 C
3 C
glucose → → → → → pyruvate
3 C
1 C
Step 2: Oxidation of pyruvate
▪
Pyruvate enters mitochondria◆ 3 step oxidation process
◆ releases 1 CO2 (count the carbons!) ◆ reduces NAD → NADH (stores energy) ◆ produces acetyl CoA
▪ Acetyl CoA enters Krebs cycle
◆ where does CO2 go?
NAD NADH 3 C 2 C 1 C
pyruvate acetyl CoA + CO2
[
Pyruvate oxidized to Acetyl CoA
Yield = 2C sugar + CO2 + NADH
reduction
Krebs cycle
▪
aka Citric Acid Cycle◆ in mitochondrial matrix ◆ 8 step pathway
▪ each catalyzed by specific enzyme
▪ step-wise catabolism of 6C citrate molecule
▪
Evolved later than glycolysis◆ does that make evolutionary sense?
▪ bacteria →3.5 billion years ago (glycolysis)
▪ free O2 →2.7 billion years ago (photosynthesis)
▪ eukaryotes →1.5 billion years ago (aerobic respiration (organelles)
1937
|
1953
Step 3: Kreb’s Cycle
This happens twice for each glucose
molecule
4C 6C 4C 4C 4C 2C 6C 5C 4C CO2 CO2 citrate acetyl CoA
Count the carbons and electron carriers!
x
2
3C pyruvate reduction of electron carriers NADH NADH FADH2 NADH ATP This happens twice for each glucoseSo we fully oxidized
glucose
C6H12O6
↓
CO2
& ended up with 4 ATP!
▪
Krebs cycleproduces large quantities of
electron carriers
◆ NADH ◆ FADH2
◆ stored energy! ◆ go to ETC
Energy accounting of Krebs cycle
▪
Net gain = 2 ATP= 6 NADH + 2 FADH2
3 NAD + 1 FAD 3 NADH + 1 FADH2
1 ADP 1 ATP
2x
acetyl - CoA → → → → → → → → →
CO2
]
ATP accounting so far…
▪
Glycolysis→
2 ATP▪
Kreb’s cycle→
2 ATP▪
Life takes a lot of energy to run, need toextract more energy than 4 ATP!
Mitochondria
▪
Double membrane◆ outer membrane ◆ inner membrane
▪ highly folded cristae*
▪ intermembrane space
◆ matrix
STAGE 4: Oxidative Phosphorylation
▪
the very controlled breakdown ofglucose to produce ATP
PART A. Electron Transport Chain
a)
In the presence of oxygen, a series of (mostly) transport proteins built into the inner membrane is used to link electron transport to ATP synthesis.Electron transport chain
Intermembrane space Inner mitochondrial membrane Mitochondrial matrix Protein complex Electron flow Electron carrierNADH NAD+
FADH2 FAD
H2O ADP ATP ATP synthase
H+ H+ H+
H+
H+ H
+ H+ H+ H+ H+ H+ H+ H+ H+ + P O2
Electron Transport Chain Chemiosmosis
b) The electrons arrive using electron carriers NADH and FADH2
◆ NADH is oxidized at NADH dehydrogenase, releasing
2 electrons
◆ FADH
2 is oxidized at ubiquinone (Q) releasing 2
But what “pulls” the
Electrons flow downhill
▪ Electrons move in steps from carrier to carrier downhill to O2
◆ each carrier more electronegative
◆ controlled oxidation AND controlled release of
H2O NAD+ NADH ATP H+ H+ Controlled release of energy for synthesis of ATP Electron transport chain
2 O2
2e− 2e−
+
▪
as they travel through, the pairs ofelectrons are releasing energy which is used to move H+ from the matrix to the intermembrane space
▪
- 3 protons for every NADHAt the end
▪
the electrons have to reduce something! oxygen◆ oxygen is reduced as it picks up 2 e and 2
protons (from matrix) to make _____
▪
there are fewer protons in the matrix than in the intermembrane spacePART B: OXIDATIVE PHOSPHORYLATION
▪
a) A proton-motive force (PMF) is set up▪
inner membrane is impermeable to H+▪
the electrochemical gradient is used to synthesize ATP as H+ move through the ATP synthase channel protein▪
b) Protons (H+) travel along theconcentration gradient through the ATP synthase
◆ ATP synthase turns and releases energy to
▪ ATP synthase
◆ enzyme in inner membrane of
mitochondria
◆ only channel permeable to H+
◆ flowing H+ cause change in
shape of ATP synthase
enzyme and powers bonding of Pi to ADP
c) At the end
For every H+ proton through the ATP synthase channel 1 ATP is formed
◆ NADH yields 3 ATP
◆ FADH
2 yields 2 ATP
▪ How efficient is cellular respiration?
▪
Only about 40% efficient.In other words, a call can harvest about 40% of the energy stored in glucose.
Taking it beyond…
▪
What is the final electron acceptor inelectron transport chain?
O
2▪
So what happens if O2 unavailable?▪
ETC backs up▪
ATP production ceases▪
cells run out of energyCertain poisons interrupt critical events in cellular respiration
◆ Various poisons
▪ Block the movement of electrons
▪ Block the flow of H+ through ATP synthase
▪ Allow H+ to leak through the membrane
H+
H+
H+
H+
H+
H+ H+ H+ H+
H+ H+ H+ H+ O 2
H2O P ATP
NADH NAD+
FADH2 FAD
Rotenone Cyanide, carbon monoxide Oligomycin DNP ATP Synthase +2 ADP+
Electron Transport Chain Chemiosmosis
1 2
Peter Mitchell
▪
Proposed chemiosmotic hypothesis◆ revolutionary idea at the time
1961
|
1978
1920-1992
Summary of cellular respiration
▪ Where did the glucose come from?
▪ Where did the O2 come from?
▪ Where did the CO2 come from?
▪ Where did the H2O come from?
▪ Where did the ATP come from?
▪ What else is produced that is not listed in this equation?
▪ Why do we breathe?
Energy Yields
▪
Glucose: 686 kcal/mol▪
ATP: 7.5 kcal/mol▪
7.5 x 36 = 270 kcal/mol for all ATP'sproduced
▪
270 / 686 = 39% energy recovered fromAnaerobic: Lactic Acid Fermentation
▪ occurs in humans and other mammals
◆ The product of Lactic Acid fermentation, lactic acid, is toxic to mammals
◆ This is the "burn" felt when undergoing strenuous activity
▪ The only goal of fermentation reactions is to convert NADH to NAD+ (to use in glycolysis).
▪ No energy is gained
▪ Note differences - anaerobic respiration - 2 ATP's produced (from glycolysis), aerobic respiration - 36 ATP's produced (from
glycolysis, Krebs cycle, and Oxidative Phosphorylation)
◆ Carbohydrates, fats, and proteins can all
fuel cellular respiration
▪ When they are converted to molecules that enter glycolysis or the citric acid cycle
OXIDATIVE PHOSPHORYLATION
(Electron Transport and Chemiosmosis)
Food, such as peanuts
Carbohydrates Fats Proteins
Sugars Glycerol Fatty acids Amino acids
Amino groups
Beyond glucose: Other carbohydrates
▪
Glycolysis accepts a wide range ofcarbohydrates fuels
◆ polysaccharides → → → glucose
▪ ex. starch, glycogen
◆ other 6C sugars → → → glucose
▪ ex. galactose, fructose
hydrolysis
▪
Proteins → → → → → amino acidsBeyond glucose: Proteins
hydrolysis
amino group = waste product
excreted as ammonia, urea,
or uric acid
enter
Krebs cycle as acetyl CoA
Beyond glucose: Fats
▪
Fats → → → → → glycerol & fatty acids◆ glycerol (3C) → → PGAL → → glycolysis ◆ fatty acids →
hydrolysis 2C acetyl groups → acetyl coA → Krebs cycle glycerol enters glycolysis
as PGAL
Carbohydrates vs. Fats
fat
carbohydrate
▪
Fat generates 2x ATP vs. carbohydrate◆ more C in gram of fat
◆ more O in gram of carbohydrate
▪ Coordination of
digestion & synthesis
◆ by regulating enzyme
▪ Digestion
◆ digestion of
carbohydrates, fats & proteins
▪ all catabolized through same pathways
▪ enter at different points
◆ cell extracts energy
from every source
Metabolism
CO
Metabolism
Krebs cycle
intermediaries → →
amino acids pyruvate → → glucose
acetyl CoA → → fatty acids
▪ Coordination of digestion & synthesis
◆ by regulating enzyme
▪ Synthesis
◆ enough energy?
build stuff!
◆ cell uses points in glycolysis
& Krebs cycle as links to pathways for synthesis
▪ run the pathways “backwards”
⬥ eat too much fuel, build fat
Cells are versatile &
▪
Food molecules provide raw materials for biosynthesis◆ Cells use some food molecules and
intermediates from glycolysis and the citric acid cycle as raw materials
◆ This process of biosynthesis
▪ Consumes ATP
ATP needed to drive biosynthesis
ATP CITRIC ACID CYCLE GLUCOSE SYNTHESIS Acetyl
CoA Pyruvate G3P Glucose
Amino groups
Amino acids Fatty
acids Glycerol Sugars
Carbohydrates Fats
Proteins
Cells, tissues, organisms
▪ The fuel for respiration ultimately comes from photosynthesis
◆ All organisms
▪ Can harvest energy from organic molecules
◆ Plants, but not animals
▪ Can also make these molecules from inorganic sources by the process of photosynthesis