Chapter 27 (continued)Chapter 27 (continued)

Specific Catabolic Specific Catabolic Pathways:Pathways:Carbohydrate, Lipid & Carbohydrate, Lipid & Protein MetabolismProtein Metabolism

1.

2. 3.

Fatty Acids and EnergyFatty Acids and Energy• Fatty acids in triglycerides are the principal storage form of energy for most organisms.

• The energy yield per gram of fatty acid oxidized is greater than that per gram of carbohydrate oxidized.

C6H12O6 + 6O2

CH3(CH2)14COOH + 23O2

6CO2 + 6H2O

16CO2 +16H2OPalmitic acid

Glucose

Energy(kcal•mol-1)

Energy(kcal•g-1)

686 3.8

2,340 9.3

• five enzyme-catalyzed reactions• cleaves carbon atoms two at a time from the carboxyl end of a fatty acid.

-Oxidation-Oxidation

-Oxidation-Oxidation

-Oxidation-Oxidation• Reaction 1: Reaction 1: the fatty acid is activated by conversion to an acyl CoA; activation is equivalent to the hydrolysis of two high-energy phosphate anhydrides.

R-CH2-CH2-C-OHO

ATP CoA-SH

R-CH2-CH2-C-SCoAO

AMP 2Pi

+ +

+ +

A fatty acid

An acyl CoA

-Oxidation-Oxidation• Reaction 2: Reaction 2: oxidation of the , carbon-carbon single bond to a carbon-carbon double bond.

R-CH2-CH2-C-SCoAO

An acyl-CoA

+FADO

HC C

C-SCoA

R H

+ FADH2

A trans enoyl-CoA

acyl-CoA dehydrogenase

-Oxidation-Oxidation• Reaction 3: Reaction 3: hydration of the C=C double bond to give a 2° alcohol.

• Reaction 4: Reaction 4: oxidation of the alcohol to a ketone.

+ H2O

An L--hydroxyacyl-CoA

C

OH

CH2-C-SCoARH

Oenoyl-CoAhydrataseH

C CC-SCoA

R HA trans enoyl-CoA

O

C

OH

CH2-C-SCoAHR

ONAD+

R-C-CH2-C-SCoAO O

NADH H+

-Hydroxyacyl-CoA

-Ketoacyl-CoA

+

-hydroxyacyl-CoAdehydrogenase

+

+

-Oxidation-Oxidation• Reaction 5:Reaction 5: cleavage of the carbon chain by a molecule of CoA-SH.

R-C-CH2-C-SCoA

OO

CoA-SH

R-C-SCoA

O O

CH3C-SCoA

-Ketoacyl-CoA

+

Coenzyme A

+

An acyl-CoA Acetyl-CoA

thiolase

-Oxidation-Oxidation• This cycle of reactions is then repeated on the shortened fatty acyl chain and continues until the entire fatty acid chain is degraded to acetyl CoA.

• -Oxidation of unsaturated fatty acids proceeds in the same way, with an extra step that isomerizes the cis double bond to a trans double bond.

CH3(CH2)16C-SCoAO

8NAD+8CoA-SH

9CH3C-SCoAO

8FAD

8NADH8FADH2

Octadecanoyl-CoA(Stearyl-CoA)

+

+Acetyl-CoA

eight cycles of -oxidation

Energy Yield from Energy Yield from --OxidationOxidation

• Yield of ATP per mole of stearic acid (C18). ATPStepChemical Step Happens

1

2

4

Activation (stearic acid -> stearyl CoA)

Oxidation (acyl CoA ->trans-enoyl CoA)produces FADH2Oxidation (hydroxy-

acyl CoA to ketoacyl

CoA) produces NADH +H+

Oxidation of acetyl CoAby the common metabolicpathway, etc.

Once

8 times

8 times

9 times

-2

16

24

108

TOTAL 146

Glycolysis TOTAL 36

• IF lauric acid (1) is metabolized through -Oxidation,

• what are the products of the reaction after 3 turns of the spiral?

Challenge QuestionChallenge Question

(1)

• Which C-18 fatty acid yields the greater amount of Energy:

• Saturated stearic acid?

• Monounsaturated oleic acid?

Confirming your knowledgeConfirming your knowledge

Formation of Ketone bodiesFormation of Ketone bodies from lack of glucose from lack of glucose

• A little Glucose needed to fully run -Oxidation

ββ-Oxidation-Oxidation

Formation of Ketone Bodies for Energy(Low glucose levels)

headaches.. ?

Ketone Bodies, see p. Ketone Bodies, see p. 677-8677-8

CH3-CH-CH2-COO-OH

CH3CCH2C-SCoA

O O

NADH

HS-CoA

CH3-C-CH3

O

NAD+ + H+

CH3-C-CH2-COO-

O

2CH3C-SCoAO

CO2

Acetyl-CoA Acetoacetyl-CoA

Acetoacetate -Hydroxybutyrate

AcetoneCH3-CH-CH2-COO-

OH

CH3CCH2C-SCoA

O O

NADH

HS-CoA

CH3-C-CH3

O

NAD+ + H+

CH3-C-CH2-COO-

O

2CH3C-SCoAO

CO2

Acetyl-CoA Acetoacetyl-CoA

Acetoacetate -Hydroxybutyrate

Acetone

CH3-CH-CH2-COO-OH

CH3CCH2C-SCoA

O O

NADH

HS-CoA

CH3-C-CH3

O

NAD+ + H+

CH3-C-CH2-COO-

O

2CH3C-SCoAO

CO2

Acetyl-CoA Acetoacetyl-CoA

Acetoacetate -Hydroxybutyrate

Acetone

• e.g.e.g. acetone, B-hydroxybutyrate, and acetoacetate;

• are formed principally in liver mitochondria.• can be used as a fuel in most tissues and organs.

• occurs when acetyl CoA builds up • (due to limited glucose levels) • vs the amt. of oxaloacetate available • to react with it + take it into the • Citric Acid Cycle

• for example when:• intake is high in lipids and low in carbohydrates.• diabetes is not suitably controlled.• Starvation occurs.

Ketone Bodies are Ketone Bodies are formedformed

Challenge QuestionChallenge Question• What happens to the oxaloacetate produced

from carboxylation of phosphoenolpyruvate?

(i.e. where does it go and or where is it needed?)

?

Protein CatabolismProtein CatabolismFigure 27.7 Overview of Protein catabolism.

Nitrogen of Amino Nitrogen of Amino AcidsAcids• A. -NH2 groups move freely by TransaminationTransamination• Amino acids transfer amino groups to -ketoglutarate

Glutamate . . .

Nitrogen of Amino AcidsNitrogen of Amino Acids

• B. Oxidative Deamination nitrogens to be excreted are collected in glutamate, which is oxidized to -ketoglutarate and NH4

+.

• NH4+ then enters the urea cycle.

COO-

CH-NH3+

CH2

CH2

COO-

H2O

NAD+ NADHCOO-

C=O CH2

CH2

COO-

NH4+

Glutamate -Ketoglutarate

++

The Urea Cycle – Overview The Urea Cycle – Overview • a cyclic pathway that produces urea from CO2 and NH4

+.

For step details see p. 681-683

The Urea Cycle p.681-682The Urea Cycle p.681-682

(Urine)

The Urea Cycle (cont.)The Urea Cycle (cont.)

Challenge QuestionChallenge Question• NH3 and NH4 are both H2O soluble and could easily be excreted in urine.

• Why does the body convert them to Urea rather then excreting them directly?

Challenge Question 2Challenge Question 2• What are the molecular sources of Nitrogen in Urea?

Hint: see Urea Cycle ReactionsSteps 1-2 and 3

p.681-682

Heme CatabolismHeme Catabolism• When red blood cells are destroyed:

• globin is hydrolyzed to amino acids to be reused.• iron is preserved in ferritin, an iron-carrying protein, and reused.

• heme is converted to bilirubin in spleen removed from blood (liver)

• then transferred to gallbladder (stored in the bile)• finally excreted in the feces.• When balance upset [high bilirubin] in blood jaundice:

(yellowing of face and eyes)• indicates Liver, spleen or gallbladder complications. . .

Final Challenge Final Challenge QuestionQuestion• Why is High bilirubin content in the

blood an indication of liver disease?