chapter 14 slides 2017 - calvin university

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CHAPTER 14: Metabolism and Bioenergetics

SUMMARY OF CATABOLISM• Your body is capable of

“burning” many sorts of fuel to produce ATPØ Carbohydrates

Ø Lipids

Ø Proteins

• All three “fuels” feed into the citric acid cycle to complete catabolism:Ø Begins with acetyl-CoAØ Requires O2

Ø Occurs in the mitochondria

• 14.1 Acetyl CoA and the Citric Acid Cycle

• 14.2 Oxidative Phosphorylation

• 14.3 Entropy and Bioenergetics (not covered)


OUTLINE

• Acetyl CoA is produced between the second & third stages of carbohydrate catabolism:

Ø Both proteins & fat can also can be converted into acetyl-CoA to produce ATP

• Further catabolism of acetyl-CoA forms NADH & FADH2 during the citric acid cycle.Ø NADH & FADH2 are re-oxidized to make ATP


ACETYL-CoA PRODUCTION FROM PYRUVATE

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• Acetyl CoA is a complex molecule consisting of pantothenic acid (vitamin B5), a thiol amine, and ADP, and the acetyl group

• Coenzyme A can carry other groups besides the acetyl in other metabolic pathways (ie. acyl chains)


ACETYL CoA

• The key to Coenzyme-A chemistry is the thiolgroup located at the very end of the molecule:


THE CHEMISTRY OF ACETYL CoA

The thiol can react with a variety of carbonyl-containingmolecules to form a high-energy thioester bond

• If oxygen is present, pyruvate is oxidized to acetyl-CoA in preparation for the citric acid cycle:Ø Requires both coenzyme A (SH-CoA) and NAD+

Ø Reaction involves the loss of a CO2 (decarboxylation)

• Reaction is catalyzed by the mitochondrial enzyme pyruvate dehydrogenase

CHAPTER 12: Carbohydrates: Structure and Function

OXIDATION OF PYRUVATE TO ACETYL-CoA

Oxidation + CO2 loss

Oxidative Decarboxylation

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• The citric acid cycle is called a “cycle” because it begins and ends with the same molecule:


THE CITRIC ACID CYCLE

SH-CoA

The NET reaction is completeoxidation of carbons to CO2

• All eight steps of the citric acid cycle occur in the mitochondrial matrix:


CARBON ATOMS IN THE CITRIC ACID CYCLE

Citric acid cycle enzymes are in the mitochondrial matrix

• Same location as beta-oxidation• Reduced products (NADH & FADH2)

feed directly into the electron transport chain in the inner membrane

Reaction Types:

1. Redox reactions:Ø Oxidation of carbonyl

groups produces NADH (Redox A)

Ø Oxidation of an alkane to alkene produces FADH2 (Redox B)

2. Thioester hydrolysis

3. Isomerization4. Hydration


DETAILED VIEW OF THE CITRIC ACID CYCLE

Redox A

Redox A

Redox A

Redox B

Thioester hydrolysis

Thioester hydrolysis

IsomerizationHydration

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• After going thru Glycolysis and the Citric Acid Cycle, what are the net products of glucose catabolism?


PRODUCT ACCOUNTING FOR GLUCOSE

Glycolysis2 Pyruvates2 ATP2 NADH

Intermediate Step1 Acetyl-CoA1 NADH1 CO2

x 2

Citric Acid Cycle1 GTP 1 FADH2

3 NADH2 CO2

x 2

NET PRODUCTS

4 ATP/GTP 6 CO2

2 FADH2

10 NADH+


ATP PRODUCTION BY OXPHOS• Most of the ATP derived from glucose catabolism

comes from the electrons carried by NADH and FADH2:

• Oxidative phosphorylation (OXPHOS) uses energy derived from the electrons of NADH and FADH2 in order to generate ATP:Ø Requires the mitochondrial electron transport chainØ Involves addition of an inorganic phosphate (Pi) to ADP

to create ATP

Ø Only 4 ATP or GTP molecules are made directly…..


MITOCHONDRIAL ARCHITECTURE

• Mitochondria have two separate membranes:Ø Inner mitochondrial membrane

Ø Outer mitochondrial membrane

• The membranes define twounique “compartments”:Ø Intermembrane space (IMS),

between the two membranes

Ø Matrix, the region within the inner membrane

Folds in the inner mito membrane (cristae) create more surface area

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OXPHOS PROTEIN COMPLEXES• Proteins involved in the electron transport chain

and oxidative phosphorylation are found in the inner mitochondrial membrane (IMM):Ø These are transmembrane protein complexes that

actually span the inner membrane phospholipid bilayer

Electrons from NADH and FADH2 are carried through the chain, ending at oxygen as the final acceptor

4H+ + O2 à 2 H2O

e-

NADHFADH2e-

e-


ELECTRON TRANSPORT• Electrons are transferred to the FOUR electron transport

complexes by oxidation-reduction reactions in metal centers of these proteins:Ø The metal centers consist of iron or copper ions, alternately oxidizing

and reducing between Fe2+/Fe3+ or Cu1+/Cu2+

• Transfer of electrons between the complexes involves two extra “electron shuttles”:Ø Coenzyme Q = a small organic co-factor

Ø Cytochrome C = protein with heme-like cofactor (iron ion center)

What sort of redox reaction is involved in Coenzyme Q electron transfer?


DIRECTION OF ELECTRON FLOW• Electron flow is determined by relative electron

affinities for each of the components in the electron transport chain:

Ø Electrons always flow from low electron affinity to highelectron affinity: § NADH & FADH2 have low

affinity for electrons§ The final electron acceptor

(O2) has the highest affinity

Ø The difference between these electron affinities is inversely proportional to their potential energy

Low e- affinity

High e- affinity

Pote

ntia

l ene

rgy à

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ELECTRON TRANSPORT DRIVES PROTON PUMPING INTO THE IMS

The energy from electron transport is used to “pump” protons across the inner membrane……

…..this creates at pH gradient


ANALOGY TO WATER WHEEL PUMPSThe potential energy of flowing water can be harnessed to produce mechanical or electricalenergy using a water wheel

Complex I

Complex III

Complex IV

Complex II

Now imagine using this energy to run a “pump”

protons


THE REAL ELECTRON TRANSPORT CHAIN• The electron transport chain complexes are

molecular “proton pumps”• Each complex is composed of many protein

subunits that work together

http://www.nature.com/nrm/journal/v16/n6/images/nrm3997-f1.jpg

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INITIATING ELECTRON TRANSPORT• Three of the four complexes in the electron

transport chain also function as “proton pumps”:1. Complex I – receives e- from NADH à pumps H+

2. Complex II – receives e- from FADH2, but does NOT pump

3. Complex III – receives e- from Coenzyme-Q à pumps H+

4. Complex IV – receives e- from Cytochrome C à pumps H+

• Complex IV reduces molecular oxygen with the electrons it receives:

O2 + 4 H+ + 4 e- à 2 H2O Ø The deadly poison cyanide (CN-) blocks the final step

of electron transport, stopping the entire transport chain


THE PROTON GRADIENT• Protons (H+) are unable to diffuse through the

inner mitochondrial membrane by simple diffusion because they are charged:Ø There are more protons in the intermitochondrial space

(lower pH) than in the matrix (higher pH).

Ø This proton gradient is maintained through the action of the electron transport chain

H+

H+H+H+

H+H+

H+

H+

H+

H+

H+H+H+

H+H+

H+H+

H+

H+

H+


THE PROTON-MOTIVE FORCE• The proton gradient between the inner membrane

space (IMS) and matrix is another form of potential energy for the cell to use:Ø The energy in this unequal distribution of protons is

called the proton-motive force

Ø The only way for protons to diffuse back down this gradient is through ATP synthase

Ø This flow of protons is harnessed to drive ATP synthesis

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PHOSPHORYLATION OF ADP• Phosphorylation of ADP to yield ATP

requires significant energy input:

Energy + ADP + Pi ® ATP + H2O

Ø The energy for this process comes from the proton gradient set up by the electron transport chain across the IMM

• ATP synthase is the enzyme responsible for producing ATP in the mitochondria:Ø Complex protein that spans the inner

mitochondrial membrane (IMM)Ø Contains a “channel” thru which H+ flowØ Proton flow drives rotary motion to combine

ADP with inorganic phosphate (Pi)

ATP synthase is a rotary “machine”

• The electron carrying capacity of redox cofactors can be translated into specific amounts of ATP:Ø Each FADH2 à ~1.5 ATPs Ø Each NADH à ~ 2.5 ATPs


ENERGY FROM GLUCOSE OXIDATION

Glycolysis2 ATP2 NADH = 5 ATP

Citric Acid Cycle1 GTP ~ 1 ATP 1 FADH2 = 1.5 ATP3 NADH = 7.5 ATP

2x

Intermediate Step1 NADH = 2.5 ATP2x

7 ATP

5 ATP

20 ATP

32 ATPper glucose

1 glucose

2 pyruvate

2 acetyl-CoA

• The electron carrying capacity of redox cofactors can be translated into specific amounts of ATP:Ø Each FADH2 à ~1.5 ATPs Ø Each NADH à ~ 2.5 ATPs


ENERGY FROM PALMITATE OXIDATION

β-oxidation (of C16:0)8 acetyl-CoA7 FADH27 NADH

Citric Acid Cycle1 GTP ~ 1 ATP 1 FADH2 = 1.5 ATP3 NADH = 7.5 ATP

8x

10.5 ATP17.5 ATP

80 ATP

106 ATPper palmitate8 acetyl-

CoA

FA Activation Step+ SH-CoA -2 ATP1 palmitate

1 palmitoyl-CoA

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SELF-REVIEW QUESTIONS1. What important role does oxygen play in the

electron transport chain?

2. Explain how cyanide shuts down the electron transport chain.

3. What important chemical reaction is driven by the flow of protons from the intermembrane space back into the matrix?

4. What is the proton-motive force? How does it drive phosphorylation of ADP?

1. How many molecules of NAD+ are reduced to NADH in the citric acid cycle?

2. How many molecules of FAD are reduced to FADH2 in the citric acid cycle?

3. How many molecules of ADP are converted into ATP as a result of one pass through the citric acid cycle, assuming all the NADH and FADH2 are used to phosphorylate ADP to ATP?


PRACTICE PROBLEMS


METABOLISM REVIEW1. In stage 1, macromolecules

are digested through hydrolysis into molecules small enough to pass into the bloodstream.

2. In stage 2, these molecules are oxidized to form acetyl CoA or other molecules able to enter the citric acid cycle as well as NADH and FADH2, carrying electrons to electron transport.

3. In stage 3, the reduction of oxygen releases energy to drive the proton-motive force used to make ATP.

Central Biomolecule Catabolism

chapter 14 slides 2017 - calvin university

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