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