Download Camp 1 - University of California, Santa Cruz

Chapter 27 (continued)
Specific Catabolic Pathways:
Carbohydrate,
Lipid
&
Protein Metabolism
1.
2.
3.
Fatty 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.
Energy
Energy
-1
(k cal• mol ) (kcal• g -1)
C6 H1 2 O6 + 6 O2
Glucose
CH3 (CH2 ) 1 4 COOH + 2 3 O2
Palmitic acid
6 CO2 + 6 H2 O
686
3.8
1 6 CO2 +1 6 H2 O 2,340
9.3
b-Oxidation
• five enzyme-catalyzed reactions
• cleaves carbon atoms two at a time from the
carboxyl end of a fatty acid.
b-Oxidation
b-Oxidation
• 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.
O
R-CH2 -CH2 -C-OH + ATP + CoA-SH
A fatty acid
O
R-CH2 -CH2 -C-SCoA + AMP + 2 Pi
An acyl CoA
b-Oxidation
• Reaction 2: oxidation of the ,b carbon-carbon single
bond to a carbon-carbon double bond.
acyl-CoA
O
b

dehydrogenase
R- CH2 -CH2 - C-SCo A + FAD
O
An acyl-CoA
H
C-SCo A
+ FAD H2
C C
R
H
A trans enoyl-CoA
b-Oxidation
• Reaction 3: hydration of the C=C double bond to give a
2° alcohol.
O
enoyl-CoA
H
C-SCo A
hydratas e
+ H2 O
C C
R
H
A trans enoyl-CoA
OH
R
C
H
O
CH2 -C- SCoA
An L- b-hydroxyacyl-CoA
• Reaction 4: oxidation of the 2alcohol to a ketone.
OH
C
H
O
CH2 -C-SCoA
R
b-Hyd roxyacyl-CoA
+ NAD+
b-h yd roxyacyl-CoA
dehydrogenas e
O
O
R-C-CH2 -C-SCoA + NADH + H+
b-Ketoacyl-CoA
b-Oxidation
• Reaction 5: cleavage of the carbon chain by a molecule
of CoA-SH.
O
O
th iolas e
R-C-CH2 -C-SCoA + CoA-SH
b-Ketoacyl-CoA
Coenzyme A
O
O
R-C-SCoA + CH3 C-SCoA
An acyl-CoA
Acetyl-CoA
b-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.
O
CH3 ( CH2 ) 1 6 C-SCoA +
Octadecanoyl-CoA
(Stearyl-CoA)
8 CoA-SH
+
8 NAD
8 FAD
eigh t cycles of
b-oxidation
O
9 CH3 C-SCoA +
A cetyl-CoA
8 NADH
8 FADH2
• b-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.
Energy Yield from b-Oxidation
• Yield of ATP per mole of stearic acid (C18).
Step Chemical Step
1
2
4
Happens
ATP
Activation (stearic
acid -> stearyl CoA)
Oxidation (acyl CoA ->
trans -enoyl CoA)
produces FADH 2
Once
-2
8 times
16
Oxidation (hydroxyacyl CoA to ketoacyl
CoA) produces NADH +H
Oxidation of acetyl CoA
by the common metabolic
pathway, etc.
8 times
24
9 times
108
Glycolysis
+
TOTAL
146
TOTAL
36
Challenge Question
• IF lauric acid (1) is metabolized
through b-Oxidation,
• what are the products of the reaction
after 3 turns of the spiral?
(1)
Confirming your knowledge
• Which C-18 fatty acid yields
the greater amount of Energy:
• Saturated stearic acid?
• Monounsaturated oleic acid?
Formation of Ketone bodies
from lack of glucose
• A little Glucose needed to fully run b-Oxidation
β-Oxidation
Formation of Ketone Bodies for Energy
(Low glucose levels)
headaches.. ?
HS-CoA
O
NADH
O
O OH
O
-C-CH2 -COO
CH3 -CH-CH2 -COOCH3 CCH2 C-SCoA
3 C-SCoA
+
cetoacetate
NAD Acetoacetyl-CoA
+ H+ b-Hyd roxybutyrate
tyl-CoA
HS-CoA
O
O
CH3 CCH2 C-SCoA
Acetoacetyl-CoA
Ketone Bodies, see p. 677-8
O
2 CH3 C-SCoA
Acetyl-CoA
e.g. acetone, B-hydroxybutyrate, and acetoacetate;
O 2
O NADH
OH
CO
CH3 -C-CH2 -COO
CH3 -CH-CH2 -COOCH3 -C-CH3
A cetoacetate
Acetone
NAD+ + H+ b-Hyd roxybutyrate
O
NADH
OH
CH3 -C-CH2 -COOCH3 -CH-CH
A cetoacetate
NAD+ + H+ b-Hyd roxy
• are formed principally in liver mitochondria.
• can be used as a fuel in most tissues and organs.
CO2
O
CH3 -C-CH3
when
acetyl
Acetone
occurs
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
CO2
O
CH3 -C-CH3
Acetone
Ketone Bodies are formed
• for example when:
• intake is high in lipids and low in carbohydrates.
• diabetes is not suitably controlled.
• Starvation occurs.
Challenge Question
• What happens to the oxaloacetate produced
from carboxylation of phosphoenolpyruvate?
(i.e. where does it go and or where is it needed?)
?
Protein Catabolism
Figure 27.7 Overview of Protein catabolism.
Nitrogen of Amino Acids
• A. -NH2 groups move freely by Transamination
• Amino acids transfer amino groups to -ketoglutarate
 Glutamate . . .
Nitrogen of Amino Acids
• B. Oxidative Deamination
nitrogens to be excreted are collected in glutamate,
which is oxidized to -ketoglutarate and NH4+.
-
COO
+
+
NAD
CH-NH3
+ H2 O
CH2
CH2
COOGlu tamate
-
COO
NADH C=O
CH2
+ NH4 +
CH2
COO-Ketoglutarate
• NH4+ then enters the urea cycle.
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.681-682
The Urea Cycle (cont.)
(Urine)
Challenge 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 2
• What are the molecular sources of Nitrogen in Urea?
Hint: see Urea Cycle Reactions
Steps 1-2 and 3
p.681-682
Heme 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 Question
• Why is High bilirubin content in the blood an
indication of liver disease?