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Chapter 27
Specific Catabolic Pathways:
Carbohydrate,
Lipid
&
Protein Metabolism
1.
2.
3.
Glycolysis: Follow Along:
Figure 27.3
Glycolysis
• 10 enzyme-catalyzed reactions by which glucose
is oxidized to two molecules of pyruvate.
glycolys is
C6 H1 2 O6
Glucos e
HO
HO
O
2 CH3 CCOO - + 2 H+
Pyruvate
CH2 OH
O
+
OH
-D -Glucose OH
-
O O
O-P-O-P-O-AMP
-
O
-
O
ATP
hexokinas e
2+
Mg
2• During glycolysis, there
is net
conversion of 2ADP to 2ATP.
CH OPO
HO
HO
2
O
3
+
OH
C6 H1 2 O6 + 2 ADP + 2 OH
Pi
-D -Glucose 6-p hosphate
Glucose
-
O
O-P-O-AMP
O
O
2 CH3 CCOO - + 2 ATP
ADP
Pyruvate
NOTE: ATP = Energy molecule of choice
Glycolysis - Rxn 1
• reaction 1: phosphorylation of -D-glucose.
HO
HO
CH2 OH
O
O O
+ -O-P-O-P-O-AMP
OH
-D -Glucose OH
HO
HO
-
O
-
O
ATP
CH 2 OPO3
O
hexokinas e
2+
Mg
2-
OH
OH
-D -Glucose 6-p hosphate
O
+ - O-P-O-AMP
O
ADP
Glycolysis - Rxn 2
• reaction 2: isomerization of glucose 6-phosphate
to fructose 6-phosphate.
6
HO
HO
6
2-
CH2 OPO3
O
2
OH
ph os phoglu coisomeras e
1
OH
-D-Glu cose 6-phosp hate
2-
CH2 OPO3
1
CH2 OH
O
H HO
2
H
OH
HO
H
-D -Fru ctos e 6-phosp hate
Glycolysis - Rxn 2
• This isomerization is most easily seen by considering
the open-chain forms of each monosaccharide; it is
one keto-enol tautomerism followed by another.
1
CHO
H 2 OH
HO
H
H
OH
H
OH
CH2 OPO3 2 Glucose 6-p hos phate
H C OH
C OH
HO
H
H
OH
H
OH
CH2 OPO3 2(A n ened iol)
1
CH2 OH
2C O
HO
H
H
OH
H
OH
CH2 OPO3 2 Fru ctose 6-phosp hate
Glycolysis - Rxn 3
• reaction 3: phosphorylation of fructose 6-
phosphate.
6
CH2 OPO 3 2 - 1
CH2 OH
O
H HO
+ A TP
H
OH
HO
H
-D-Fructose 6-phosphate
ATP
ADP
phosphofructokinase
Mg 2 +
6
CH2 OPO 3 2 - 1
CH2 OPO 3 2 O
H HO
+ A DP
H
OH
HO
H
-D-Fructose 1,6-bisphosphate
Glycolysis - Rxn 4
• reaction 4: cleavage of fructose 1,6-bisphosphate
to two triose phosphates.
CH2 OPO3
2-
C=O
HO
H
H
al dol ase
H
OH
OH
CH2 OPO3 2 -
Fructose 1,6-b isph osp hate
CH2 OPO3 2 C=O
CH2 OH
CHO
H C OH
CH2 OPO3 2 -
D ih yd roxyacetone
p hos phate
D -Glyceraldehyde
3-p hosph ate
Glycolysis - Rxn 5
• reaction 5: isomerization of triose phosphates.
• Catalyzed by phosphotriose isomerase.
• Reaction involves two successive keto-enol
tautomerizations.
• Only the D enantiomer of glyceraldehyde 3-phosphate
is formed.
CH2 OH
C= O
CHOH
C-OH
CH2 OPO 3 2 -
CH2 OPO 3 2 -
Dihydroxyacetone
phosphate
An enediol
intermediate
CHO
H C OH
CH2 OPO 3 2 D-Glyceraldehyde
3-phosphate
Glycolysis - Rxn 6
• Reaction 6: oxidation of the -CHO group of
D-glyceraldehyde 3-phosphate.
• The product contains a phosphate ester and a highenergy mixed carboxylic-phosphoric anhydride.
CHO
H C OH
2CH2 OPO3
D -Glyceraldehyde
3-ph os phate
+
+ NAD + Pi
glyceraldeh yd e
3-p hosphate
d ehydrogenase
O
2C-OPO3
H C OH
+ NADH
2CH2 OPO3
1,3-Bis phosp hoglycerate
Glycolysis - Rxn 7
O
phosp ho2C-OPO3
O
glycerate kinas e
•
+ O-P-O-AMP
H C OH
2+
2Mg
O
CH2 OPO3
1,3-Bisp hos phoAD P
glycerate
O
phosp hoCOOO O
2C-OPO3
O
glycerate
kinas
e
+ O-P-O-P-O-AMP
H C OH
+ O-P-O-AMP
H C OH
22+
O
O
2CH
OPO
Mg
2
3
O
CH2 OPO3
3-Ph os phoglycerate
ATP
1,3-Bisp hos phoAD P
glycerate
COOO O
+ -O-P-O-P-O-AMP
H C OH
O O
CH2 OPO3 2 3-Ph os phoglycerate
ATP
Reaction 7: transfer of a phosphate group from
1,3-bisphosphoglycerate to ADP.
Glycolysis - Rxn 8 & 9
• Reaction 8: isomerization of 3-phosphoglycerate
to 2-phosphoglycerate.
phosph oglycerate
COOCOOmutas e
H C OH
H C OPO3 2 CH2 OH
CH2 OPO3 22-Ph os phoglycerate
3-Phos phoglycerate
• Reaction 9: dehydration of 2-phosphoglycerate.
COOCOOen olase
22+ H2 O
H C OPO3
C
OPO
2+
3
Mg
CH2 OH
CH2
2-Phosph oglycerate
Phosph oen olp yruvate
COO
O
2C OPO3
+ O-P-O-AMP
CH2
O-
kinas e
Mg2 +
Glycolysis - Rxn 10
AD P
os phoenol• Reaction Ph
10:
phosphate transfer
to ADP
-
COO
2C OPO3
CH2
Ph os phoenolpyruvate
pyruvate
O
+ O-P-O-AMP
OAD P
pyru vate
kinas e
Mg2 +
O O
COOC=O + O-P-O-P-O-AMP
O- OCH3
A TP
Pyruvate
O O
COOC=O + O-P-O-P-O-AMP
O- OCH3
A TP
Pyruvate
Glycolysis: SUMMARY:
1 ATP used
1 ATP used
Figure 27.3
2 ATP produced
Note: Glycer-3 phosphate X 2
2 ATP produced
Glycolysis: Summary
• The net equation for glycolysis:
C6 H1 2 O6 + 2 N A D+ + 2 HPO 4 2 - + 2 A DP
Glucos e
O
2 CH3 CCOO - + 2 NADH +
Pyruvate
glycolys is
2 ATP + 2 H 2 O + 2 H +
Confirming your knowledge
• Of the 36 molecules of ATP produced by the
complete metabolism of glucose, how many are
produced in glycolysis alone? ____
• What is the net total ATP production?
___ ATP
Total: 36 ATP
Reactions of Pyruvate:
Fig 27.4
• Pyruvate metabolized three ways:
• depends on organism & presence/absence of O2
12
aerobic conditions
p lants and animals
Acetyl CoA
13
Citric acid cycle
OH
O
- 11 anaerob ic conditions
CH3 CHCOOCH3 CCOO
contracting mu scle
Lactate
Pyruvate
10 anaerob ic conditions
CH3 CH2 OH + CO2
fermentation in yeast
Ethanol
NOTE:
Anaerobic = w/o Oxygen
Aerobic = w/ Oxygen
Reactions of Pyruvate
• A key to understanding the biochemical logic
behind two of these reactions of pyruvate is to
recognize that glycolysis needs a continuing
supply of NAD+.
• If no oxygen is present to reoxidize NADH to NAD+,
then another way must be found to reoxidize it.
Pyruvate to Lactate
• Under anaerobic (NO Oxygen) conditions, the most
important pathway for the regeneration of NAD+ is
reduction of pyruvate to lactate. Pyruvate, the oxidizing
agent, is reduced to lactate.
lactate
O
dehydrogenase
+
CH3 CCOO + NA DH + H
Pyruvate
OH
CH3 CHCOO- + NA D+
Lactate
Pyruvate to Lactate
• While reduction to lactate allows glycolysis to continue, it
increases the concentration of lactate and also of H+ in muscle
tissue
lactate
OH
C6 H1 2 O6 fermentation
2 CH3 CHCOO- + 2 H+
Glucos e
Lactate
((ACID!))
• When blood lactate reaches about 0.4 mg/100 mL, muscle tissue
becomes almost completely exhausted, esp. b/c H+ ions.
Pyruvate to Ethanol
• Yeasts and several other organisms regenerate
NAD+ by this two-step pathway:
• decarboxylation of pyruvate to acetaldehyde.
pyruvate
O
decarboxylase
+
CH3 CCOO + H
Pyruvate
O
CH3 CH + CO 2
Acetaldehyde
• Acetaldehyde is reduced to ethanol.
alcohol
O
dehydrogenase
+
CH3 CH + N AD H + H
Acetaldehyde
CH3 CH2 OH + NA D +
Ethanol
Pyruvate to Acetyl-CoA
• Under aerobic conditions, pyruvate undergoes
oxidative decarboxylation.
• The carboxylate group is converted to CO2.
• The remaining two carbons are converted to the acetyl
group of acetyl CoA.
oxidative
O
decarboxylation
CH3 CCOO - + NAD+ + CoASH
Pyruvate
O
CH3 CSCoA + CO2 + N ADH
Acetyl-CoA
Confirming your knowledge
• The end product of glycolysis (pyruvate)
cannot enter as such into the citric acid cycle.
• What is the name of the process that converts
this C3 compound to a C2 compound?
Catabolism of Glycerol
•
Glycerol enters glycolysis via dihydroxyacetone phosphate.
CH2 OH ATP
ADP
CHOH
CH2 OH 7.3 kcal/mole
Glycerol
+
NAD
CH2 OH
CHOH
CH2 OPO3 2Glycerol
1-phosph ate
3.4 kcal/mole.
NADH
CH2 OH
C=O
CH2 OPO3 2 D ihydroxyacetone
phosp hate
Challenge Question
• Which yields more Energy upon hydrolysis:
ATP or glycerol 1- phosphate and Why?
CH2 OH ATP
CHOH
CH2 OH
Glycerol
ADP
+
NAD
CH2 OH
CHOH
CH2 OPO3 2Glycerol
1-phosph ate
NADH
CH2 OH
C=O
CH2 OPO3 2 D ihydroxyacetone
phosp hate
Summary
• Glycolysis yields 2 net ATP
• ATP is the molecule of choice for cell(s) Energy
• ATP is a High E yielding molecule (7.3 kcal/mole)
• Pyruvate is the END product of Glycolysis
oxidative
O
» under aerobic conditions
 Acetyl CoA  further ATP!!!
decarboxylation
+
CH3 CCOO »+under
NADanaerobic
+ CoASH
conditions  Lactate  (muscle fatigue)
Pyruvate
O
CH3 CSCoA + CO2 + N ADH
Acetyl-CoA