BSC 2010 - Exam I Lectures and Text Pages• I. Intro to Biology (2-29)
• II. Chemistry of Life– Chemistry review (30-46)
– Water (47-57)
– Carbon (58-67)
– Macromolecules (68-91)
• III. Cells and Membranes– Cell structure (92-123)
– Membranes (124-140)
• IV. Introductory Biochemistry– Energy and Metabolism (141-159)
– Cellular Respiration (160-180)
– Photosynthesis (181-200)
Citric Acid Cycle
• Citric acid cycle completes the energy-yielding oxidation of organic molecules
• The citric acid cycle
– Takes place in the matrix of the mitochondrion
An overview of the citric acid cycle
ATP
2 CO2
3 NAD+
3 NADH
+ 3 H+
ADP + P i
FAD
FADH2
Citricacidcycle
CoA
CoA Acetyle CoA
NADH+ H+
CoA
CO2
Pyruvate(from glycolysis,2 molecules per glucose)
ATP ATP ATP
Glycolysis Citricacidcycle
Oxidativephosphorylation
Figure 9.11
Figure 9.12
Acetyl CoA
NADH
Oxaloacetate
CitrateMalate
Fumarate
SuccinateSuccinyl
CoA
-Ketoglutarate
Isocitrate
Citricacidcycle
S CoA
CoA SH
NADH
NADH
FADH2
FAD
GTP GDP
NAD+
ADP
P i
NAD+
CO2
CO2
CoA SH
CoA SH
CoAS
H2O
+ H+
+ H+ H2O
C
CH3
O
O C COO–
CH2
COO–
COO–
CH2
HO C COO–
CH2
COO–
COO–
COO–
CH2
HC COO–
HO CHCOO–
CHCH2
COO–
HO
COO–
CH
HC
COO–
COO–
CH2
CH2
COO–
COO–
CH2
CH2
C O
COO–
CH2
CH2
C O
COO–
1
2
3
4
5
6
7
8
Glycolysis Oxidativephosphorylation
NAD+
+ H+
ATP
Citricacidcycle
Figure 9.12
A closer look at the citric acid cycle
Pyruvate AcetylCoA Citric Acid Cycle
Yield from each 2 pyruvate molecules (from 1 glucose)
• 6CO2 (2 from Pyr.AcetylCoA, 4 from CAC
• 8NADH (2 from Pyr. AcetylCoA, 6 from CAC)
• 2FADH2 (All from CAC)
• 2 ATP (All from CAC)
Two pyruvates are produced from the glycolysis of each glucose molecule resulting in a total of 2 ATP from Citric Acid Cycle, and the NADH and FADH2 go to power the Electron Transport Chain
Oxidative phosphorylation• Chemiosmosis couples ETC to ATP synthesis
• ETC (fig 9.13) = collection of mostly proteins embedded in the inner mitochondrial membranes (cristae = foldings that increase SA)
• Each electron acceptor along the ETC is more electronegative than the previous O2 at the end, the final electron acceptor (most electronegative)
• NADH transfers e- to the 1st molecule of ETC (flavoprotein) in multiprotein complex I
• Ubiquinone (= small hydrophobic non-protein that’s mobile within the membrane system) transfers e- from multiprotein complex I II
• FADH2 transfers e- to the 2nd multiprotein complex (provides 1/3 less E than NADH)
• ATP is not directly made by the ETC Chemiosmosis couples this E release with making ATP
• ETC – stores energy by pumping protons from the matrix across the inner mitochondrial membrane into the intermembrane space. (fig. 9.15)
• Chemiosmosis = E stored in H+ gradient across a membrane (proton-motive force) is used to drive ATP synthesis
• ATP synthase complexes in the membrane = only place H+ can freely move along concentration gradient and back into the matrix (fig. 9.14)
Oxidative Phosphorylation
• During oxidative phosphorylation, chemiosmosis couples electron transport to ATP synthesis
• NADH and FADH2
– Donate electrons to the electron transport chain, which powers ATP synthesis via oxidative phosphorylation through chemiosmosis
The Pathway of Electron Transport• In the electron transport chain
– Electrons from NADH and FADH2
lose energy in several steps
H2O
O2
NADH
FADH2
FMNFe•S Fe•S
Fe•S
O
FAD
Cyt b
Cyt c1Cyt c
Cyt aCyt a3
2 H + + 12
III
III
IV
Multiproteincomplexes
0
10
20
30
40
50
Free
ene
rgy
(G) r
elat
ive
to O
2 (k
cl/m
ol)
Figure 9.13
NADH passes electrons to multiprotein complex I. They are then passed to Ubiquinone which transfers them to multiprotein complex II.
FADH2 passes electrons directly to multiprotein complex II.
Electrons are passed to more electron acceptors in the remaining multiprotein complexes. Finally they are passed to oxygen, the most electronegative acceptor, forming water.
ETC stores energy in an ion gradient
• At certain steps along the electron transport chain
– Electron transfer causes protein complexes to pump H+ from the mitochondrial matrix to the intermembrane space
• The resulting H+ gradient
– Stores energy
– Drives chemiosmosis in ATP synthase
– Is referred to as a proton-motive force
Chemiosmosis
• Chemiosmosis
– Is an energy-coupling mechanism that uses energy in the form of a H+ gradient across a membrane to drive cellular work
Chemiosmosis: The Energy-Coupling Mechanism
• ATP synthase
– Is the enzyme that actually makes ATPINTERMEMBRANE SPACE
H+
H+
H+
H+
H+
H+ H+
H+
P i
+ADP
ATP
A rotor within the membrane spins clockwise whenH+ flows past it down the H+
gradient.
A stator anchoredin the membraneholds the knobstationary.
A rod (for “stalk”)extending into the knob alsospins, activatingcatalytic sites inthe knob.
Three catalytic sites in the stationary knobjoin inorganic Phosphate to ADPto make ATP. MITOCHONDRIAL MATRIXFigure 9.14
Chemiosmosis and the electron transport chain
Oxidativephosphorylation.electron transportand chemiosmosis
Glycolysis
ATP ATP ATP
InnerMitochondrialmembrane
H+
H+H+
H+
H+
ATPP i
Protein complexof electron carners
Cyt c
I
II
III
IV
(Carrying electronsfrom, food)
NADH+
FADH2
NAD+
FAD+ 2 H+ + 1/2 O2
H2O
ADP +
Electron transport chainElectron transport and pumping of protons (H+),
which create an H+ gradient across the membrane
ChemiosmosisATP synthesis powered by the flowOf H+ back across the membrane
ATPsynthase
Q
Oxidative phosphorylation
Intermembranespace
Innermitochondrialmembrane
Mitochondrialmatrix
Figure 9.15
Energy Transfer Efficiency• Complete oxidation of 1 mole of glucose releases
686 kcal of energy
• Phosphorylation of ADP ATP stores 7.3 kcal/mol
• Respiration makes 38 ATP (x 7.3 kcal/mol) = 277.4 kcal (40% of 686 kcal)
• Only about 40% of E stored in glucose is used to make ATP (the rest is lost as HEAT)
An Accounting of ATP Production by Cellular Respiration
• During respiration, most energy flows in this sequence
– Glucose to NADH to electron transport chain to proton-motive force to ATP
Three main processes in this metabolic enterprise
Electron shuttlesspan membrane
CYTOSOL 2 NADH
2 FADH2
2 NADH 6 NADH 2 FADH22 NADH
Glycolysis
Glucose2
Pyruvate
2AcetylCoA
Citricacidcycle
Oxidativephosphorylation:electron transport
andchemiosmosis
MITOCHONDRION
by substrate-levelphosphorylation
by substrate-levelphosphorylation
by oxidative phosphorylation, dependingon which shuttle transports electronsfrom NADH in cytosol
Maximum per glucose:About
36 or 38 ATP
+ 2 ATP + 2 ATP + about 32 or 34 ATP
or
Figure 9.16
About 40% of the energy in a glucose molecule is transferred to ATP during cellular respiration, making approximately 38 ATP
FermentationFermentation = extension of glycolysis that can generate ATP solely by substrate-
level phosphorylation (as long as there’s plenty of NAD+) by transferring e- from NADH to pyruvate (or its derivatives). Does not use oxygen.
2 common types of fermentation:
1. Alcohol fermentation (fig 9.17a)
• Pyruvate ethanol (2 steps)
– 1st step: releases CO2 from pyruvate acetaldehyde (2-C)
– 2nd step: acetaldehyde reduced by NADH ethanol
– NAD+ continues glycolysis
• Used to make beer/wine and in baking
2. Lactic acid fermentation (fig 9.17b)
• Pyruvate lactate
• Used to make cheese & yogurt (bacteria and fungi)
• Your muscles also make ATP this way when O2 is scarce
Facultative anaerobes = organisms that can either use pyruvate in fermentation OR in respiration (depending of O2 availability)
To make the same amt of ATP an organism w/o O2 would have to consume sugar at a much faster rate
Fermentation enables some cells to produce ATP w/o oxygen:
• In aerobic respiration, O2 pulls e- through the ETC
– Yields up to 19 times more ATP
• w/o O2, other e- acceptors can be used
• Glycolysis = exergonic process that uses NAD+ (not O2) as an e- acceptor
Fermentation
• Fermentation enables some cells to produce ATP without the use of oxygen
• Cellular respiration
– Relies on oxygen to produce ATP
• In the absence of oxygen
– Cells can still produce ATP through fermentation
Glycolysis
• Glycolysis
– Can produce ATP with or without oxygen, in aerobic or anaerobic conditions
– Under anaerobic conditions, it couples with fermentation to produce ATP
Types of Fermentation
• Fermentation consists of
– Glycolysis plus reactions that regenerate NAD+, which can be reused by glyocolysis
Alcohol Fermentation
• In alcohol fermentation
– Pyruvate is converted to ethanol in two steps, one of which releases CO2
2 ADP + 2 P1 2 ATP
GlycolysisGlucose
2 NAD+ 2 NADH
2 Pyruvate
2 Acetaldehyde 2 Ethanol
(a) Alcohol fermentation
2 ADP + 2 P1 2 ATP
GlycolysisGlucose
2 NAD+ 2 NADH
2 Lactate
(b) Lactic acid fermentation
HH OH
CH3
C
O –
OCC O
CH3
HC O
CH3
O–
C O
C O
CH3OC O
C OHH
CH3
CO22
Figure 9.17
2 pyruvate
Lactic Acid Fermentation
• During lactic acid fermentation
– Pyruvate is reduced directly by NADH to form lactate as a waste product
2 ADP + 2 P1 2 ATP
GlycolysisGlucose
2 NAD+ 2 NADH
2 Pyruvate
2 Acetaldehyde 2 Ethanol
(a) Alcohol fermentation
2 ADP + 2 P1 2 ATP
GlycolysisGlucose
2 NAD+ 2 NADH
2 Lactate
(b) Lactic acid fermentation
HH OH
CH3
C
O –
OCC O
CH3
HC O
CH3
O–
C O
C O
CH3OC O
C OHH
CH3
CO22
Figure 9.17
2 pyruvate
Fermentation and Cellular Respiration Compared
• Both fermentation and cellular respiration
– Use glycolysis to oxidize glucose and other organic fuels to pyruvate
• Fermentation and cellular respiration
– Differ in their final electron acceptor
• Cellular respiration
– Produces more ATP
Pyruvate
• Pyruvate is a key juncture in catabolismGlucose
CYTOSOL
PyruvateNo O2 presentFermentation
O2 present Cellular respiration
Ethanolor
lactate
Acetyl CoAMITOCHONDRION
Citricacidcycle
Figure 9.18
The Evolutionary Significance of Glycolysis
• Glycolysis
– Occurs in nearly all organisms
– Probably evolved in ancient prokaryotes (3.5 bya) before there was oxygen in the atmosphere
– They did not have oxygen or mitochondria
Versatility in Catabolism
• Glycolysis and the citric acid cycle connect to many other metabolic pathways
• Our bodies generally use many sources of energy in respiration (fig 9.19) regulated by feedback inhibition (fig 9.20)
• Carbohydrates simple sugars, enter glycolysis
• Proteins amino acids (used to build new proteins)
– Excess amino acids are deaminated intermediates of glycolysis or citric acid cycle, or form acetyl CoA
• Fats gylcerol + fatty acids (where most E stored)
– Gylcerol intermediate of glycolysis
– Beta oxidation breaks fatty acids down to 2-C fragments citric acid cycle as acetyl CoA
The Versatility of Catabolism
• Catabolic pathways
– Funnel electrons from many kinds of organic molecules into cellular respiration
• Glycolysis and the citric acid cycle connect to many other metabolic pathways
The catabolism of various molecules from food
Amino acids
Sugars Glycerol Fattyacids
GlycolysisGlucose
Glyceraldehyde-3- P
Pyruvate
Acetyl CoA
NH3
Citricacidcycle
Oxidativephosphorylation
FatsProteins Carbohydrates
Figure 9.19
Biosynthesis (Anabolic Pathways)
• The body
– Uses small molecules to build other substances
• These small molecules
– May come directly from food or through glycolysis or the citric acid cycle
Regulation of Cellular Respiration via Feedback Mechanisms
• Cellular respiration
– Is controlled by allosteric enzymes at key points in glycolysis and the citric acid cycle
– Releases energy, but does not produce it.
Glucose
Glycolysis
Fructose-6-phosphate
Phosphofructokinase
Fructose-1,6-bisphosphateInhibits Inhibits
Pyruvate
ATPAcetyl CoA
Citricacidcycle
Citrate
Oxidativephosphorylation
Stimulates
AMP
+– –
Figure 9.20