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CHEM 109C – Zhang
Metabolism Overview
CLAS F10
From our food…
Stage (Location)
Fats
Carbohydrates (glycogen, starch)
Proteins
+ 3 H2O
+ H2O
+ H2O
↓
(Sect. 25.6, Fig 25.3)
↓
(Sect. 25.7, Fig 25.4)
endo and exopeptidases ↓
OH
O
1 Digestion (stomach &
intestines)
O
HO
R
O
-
H
Glycerol
O
H
OH
OH
3 Fatty Acids
O OH
H
OH
+
NH3
HO
H
H
-
Phe as example
(Amino Acids)
OH
Glucose (monosaccharides)
acyl-CoA synthase
↓ CoASH → ADP, HPO42-
glycerol kinase
↓ ATP, Mg2+ → ADP
hexokinase
↓ ATP, Mg2+ → ADP
phenylalanine hydroxylase ↓
OPi
O
O
O OH
H
H
R
H
OH
SCoA
fatty acid acyl-CoA (a thioester)
-
+
HO
H
H
2 Formation of AcetylCoA
O
NH3
HO
Tyr
OH
glucose-6-phosphate
acyl-CoA dehydrogenase
↓ FAD → FADH2
PiO
OH
OH
glycerol-3-phosphate
PiO
H
HO
OH
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O
H
H
fructose-6-phosphate
enoyl-CoA hydratase
↓ H2O
O
OH
O
O
R
SCoA 
-unsaturated fatty acid acyl-CoA
tyrosine aminotransferase
↓ PLP
phosphoglucose isomerase ↓↑
phosphofructokinase
↓ ATP, Mg2+ → ADP
OH
-
O
HO
p-hydroxyphenylpyruvate
p-hydroxyphenylpyruvate dioxygenase
↓
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CHEM 109C – Zhang
Metabolism Overview
CLAS F10
PiO
OH
O
H
OH
H
glycerol phosphate dehydrogenase
↓ NAD+ → NADH, H+
-
O
OPi
HO
homogentisate
fructose-1,6-diphosphate
3-L-hydroxyacyl-CoA dehydrogenase
↓ NAD+ → NADH, H+
O
HO
H
R
SCoA 
-hydroxy fatty acid acyl-CoA
OH
OH
O
O
homogentisate dioxygenase
↓
aldolase ↓↑
OPi
O
OPi
O
H
O
O
O
R
SCoA 
-keto fatty acid acyl-CoA
HO
glyceraldehyde-3- phosphate
phosphate
glyceraldehydes-3-phosphate dehydrogenase
↓↑ NAD+ + HPO42- → NADH, H+
↓ CoASH
PiO
↓
O
H
R
↓
triosephosphate isomerase
dihydroxyacetone
OH
PiO
O
O
OH
HO
dihydroxyacetone phosphate
(can enter glycolysis)
-ketoacyl-CoA thiolase
PiO
O
1,3-diphosphoglycerate
SCoA +
H3C
SCoA
O
phophoglycerate kinase
↓↑ ADP → ATP
Fatty Acyl-CoA + Acetyl-CoA
O
H
-
O
O
-
O
H3C
SCoA
+
O
Acetyl-CoA + fumarate
OH
PiO
3-phosphoglycerate
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Page 2 of 8
-
CHEM 109C – Zhang
Metabolism Overview
CLAS F10
phosphoglycerate mutase ↓↑
O
-
O
H
OPi
HO
2-phosphoglycerate
enolase ↓↑
O
-
O
H2C
OPi
phosphoenol pyruvate + H2O
pyruvate kinase
↓↑ ADP → ATP
O
-
H 3C
O
O
Pyruvate
Overall Reaction: glucose → 2 pyruvate + 2 ATP + 2 NADH
pyruvate dehydrogenase system/complex
↓ TPP, lipoate, CoASH, FAD, NAD+
O
H3C
SCoA
Acetyl-CoA + CO2
Overall Reaction: pyruvate → acetyl-CoA + CO2 + NADH
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Page 3 of 8
CHEM 109C – Zhang
Metabolism Overview
CLAS F10
3 Citric Acid Cycle, Kreb’s
Cycle (mitochondria)
Sect. 25.10
Overall Reaction: Acetyl-CoA → 2 CO2 + 3 NADH + GTP + FADH2
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Page 4 of 8
CHEM 109C – Zhang
Metabolism Overview
CLAS F10
nucleoside diphosphokinase
GTP + ADP
4 Oxidative
Phosphorylation
(mitochondria)
Sect. 25.11
GDP + ATP
NADH
NAD+ + 3 ATP
FADH2
FAD + 2 ATP
Another way of looking at the catabolism of fats:
Step
1
2
Reaction (type)
fat + 3 H2O → glycerol (see below) + 3 fatty acids (hydrolysis)
fatty acid + CoASH + ATP → fatty acid acyl-CoA + ADP, HPO42- (formation of thioester)
3
4
5
6
fatty acid acyl-CoA + FAD → -unsaturated fatty acid acyl-CoA + FADH2 (oxidation)
-unsaturated fatty acid acyl-CoA + H2O → -hydroxy fatty acid acyl-CoA + H+ (hydration)
-hydroxy fatty acid acyl-CoA + NAD+ → -keto fatty acid acyl-CoA + NADH + H+ (oxidation)
-keto fatty acid acyl-CoA + CoASH → acetyl-CoA + fatty acid acyl-CoA
(return to step 3 and continue removing 2 Cs from fatty acid acyl-CoA as acetyl-CoA.)
1g
2g
3g
Glycerol + ATP → glycerol-3-phosphate + ADP
Glycerol-3-phosphate + NAD+ → dihydroxyacetone phosphate + NADH
4g+
Enzyme
acyl-CoA synthase
acyl-CoA dehydrogenase
enoyl-CoA hydratase
3-L-hydroxyacyl-CoA dehydrogenase
Coenzyme
CoASH
FAD
NAD+
-ketoacyl-CoA thiolase
CoASH
glycerol kinase
glycerolphosphate dehydrogenase
triosephosphate isomerase
Mg2+
NAD+
dihydroxyacetone phosphate
glygeraldehyde-3-phosphate
glygeraldehyde-3-phosphate can join glycolysis pathway to form pyruvate → acetyl-CoA
Overall: 3 FA acyl-CoA + glycerol →3 shorter FA acyl-CoA + 4 acetyl-CoA + 5 NADH + 3 FADH2 + 2 ATP
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Page 5 of 8
CHEM 109C – Zhang
Metabolism Overview
CLAS F10
Another way of looking at Glycolysis:
Step
1
2
3
Reaction (type)
glucose + ATP → glucose-6-phosphate + ADP + H+ (phosphoryl transfer)
glucose-6-phosphate
fructose-6-phosphate (isomerization)
fructose-6-phosphate + ATP → fructose-1,6-diphosphate + ADP + H+
(phosphoryl transfer)
Enzyme
Coenzyme
hexokinase
phosphoglucose isomerase
Mg2+
phosphofructokinase
Mg2+
4
fructose-1,6-diphosphate
dihydroxyacetone phosphate +
glyceraldehyde-3-phosphate (aldol cleavage)
5
dihydroxyacetone phosphate
(isomerization)
6
2 glyceraldehyde-3-phosphate + 2 HPO32- + 2 NAD+
2 1,3+
diphosphoglycerate + 2 NADH + 2 H (phosphorylation, oxidation)
7
2 1,3-diphosphoglycerate + 2 ADP
(phosphoryl transfer)
8
2 3-phosphoglycerate
isomerization)
9
2 2-phosphoglycerate
2 phosphoenolpyruvate + 2 H2O
enolase
(dehydration)
2 phosphoenolpyruvate + 2 ADP + 2 H+ → 2 pyruvate + ATP (phosphoryl
pyruvate kinase
transfer)
Overall: glucose → 2 pyruvate + 2 NADH + 2 ATP / glucose → 2 acetyl-CoA + 4 NADH + 2 ATP
10
Know all mechanisms!
glyceraldehyde-3-phosphate
2 3-phosphoglycerate + ATP
2 2-phosphoglycerate (phosphoryl shift,
Go (kcal/mol)
Go = -28.9]
-4.0
+0.4
-3.4
aldolase
-5.7
triosephosphate isomerase
+1.8
glyceraldehyde-3-phosphate
dehydrogenase
NAD+, HPO32-
2(+1.5) = +3.0
phosphoglycerate kinase
2(-4.5) = -9.0
phosphoglycerate mutase
2(+1.1) = +2.2
2(+0.4) = +0.8
2(-7.5) = -15.0
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CHEM 109C – Zhang
Metabolism Overview
CLAS F10
Other ways of looking at the Citric Acid Cycle:
Know all mechanisms!
Page 7 of 8
CHEM 109C – Zhang
Metabolism Overview
Step
Reaction (type)
1
2
acetyl-CoA + oxaloacetate + H2O → citrate + CoASH + H+ (condensation)
3
isocitrate + NAD+
4
-ketoglutarate + NAD+ + CoASH
oxidation)
5
succinyl-CoA + HPO32- + GDP
6
succinate + FAD
7
fumarate + H2O
8
L-malate + NAD+
citrate
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isocitrate (isomerization)
-ketoglutarate + CO2 + NADH + H+ (decarboxylation, oxidation)
succinyl-CoA + CO2 + NADH + H+ (decarboxylation,
succinate + GTP + CoASH (phosphorylation)
fumarate + FADH2 (oxidation)
L-malate (hydration)
CLAS F10
Enzyme
Coenzyme
citrate synthase
aconitase
Fe-S
isocitrate dehydrogenase
-ketoglutarate
dehydrogenase
(system/complex)
succinyl-CoA synthase
succinate dehydrogenase
NAD+
(Lipoate,
FAD, TPP),
NAD+
-2.0
-7.2
-0.4
FAD, Fe-S
fumarase
malate dehydrogenase
oxaloacetate + NADH + H+ (oxidation)
Overall: acetyl-CoA → 2 CO2 + 3 NADH + FADH2 + GTP
Go (kcal/mol)
Go = -9.4]
-7.5
+1.5
0
-0.9
NAD+
+7.1
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