2. Introduction
In most living organisms, the pathways by which
a compound is synthesized are usually different
from the pathways by which it is degraded; two
reasons are
1. Flexibility: If a normal biosynthetic pathway is
blocked, the organism can often use the reverse
of the degradation pathway for synthesis.
2. Overcoming Le Châtelier’s principle:
– We can illustrate by this reaction:
3. Introduction
– Phosphorylase catalyzes both the forward and reverse
reactions.
– A large excess of phosphate would drive the reaction to the
right; that is, drive the hydrolysis of glycogen.
– To provide an alternative pathway for the synthesis of
glycogen, even in the presence of excess phosphate:
Most synthetic pathways are different from the
degradation pathways. Most also differ in location and in
energy requirements.
4. Carbohydrate Biosynthesis
We discuss the biosynthesis of carbohydrates under three
headings:
– Conversion of CO2 to glucose in plants.
– Synthesis of glucose in animals and humans.
– Conversion of glucose to other carbohydrates.
Conversion of CO2 to carbohydrates in plants
– Photosynthesis takes place in plants, green algae, and
cyanobacteria.
5. Synthesis of Glucose
Gluconeogenesis: The synthesis of glucose from
noncarbohydrate sources.
– These sources are most commonly pyruvate, citric acid
cycle intermediates, and glucogenic amino acids.
– Gluconeogenesis is not the exact reversal of glycolysis;
that is, pyruvate to glucose does not occur by reversing
the steps of glucose to pyruvate.
– There are three irreversible steps in glycolysis:
---Phosphoenolpyruvate to pyruvate + ATP.
---Fructose 6-phosphate to fructose 1,6-bisphosphate.
---Glucose to glucose 6-phosphate.
– These three steps are reversed in gluconeogenesis, but by
different reactions and using different enzymes.
8. Other Carbohydrates
Glucose is converted to other hexoses and to
di-, oligo-, and polysaccharides.
– The common step in all of these syntheses is
activation of glucose by uridine triphosphate
(UTP) to form uridine diphosphate glucose (UDP-
glucose) + Pi .
9. Other Carbohydrates
– glycogenesis: The synthesis of glycogen from
glucose.
– The biosynthesis of other di-, oligo-, and
polysaccharides also uses this common activation
step to form an appropriate UDP derivative.
10. The Cori Cycle
The Cori cycle.
Lactate from
glycolysis in muscle
is transported to
the liver, where
gluconeogensis
converts it back to
glucose.
11. Fatty Acid Biosynthesis
While degradation of fatty acids takes place in
mitochondria, the majority of fatty acid synthesis
takes place in the cytosol.
These two pathways have in common that they both
involve acetyl CoA.
– Acetyl CoA is the end product of each spiral of
b-oxidation.
– Fatty acids are synthesized two carbon atoms at a time
– The source of these two carbons is the acetyl group of
acetyl CoA.
The key to fatty acid synthesis is a multienzyme
complex called acyl carrier protein, ACP-SH.
12. Fatty Acid Biosynthesis
Figure 29.3 The
biosynthesis of
fatty acids.
– ACP has a side
chain that carries
the growing fatty
acid
– ACP rotates
counterclockwise,
and its side chain
sweeps over the
multienzyme
system (empty
spheres).
13. Fatty Acid Biosynthesis
Step 1: Acyl carrier protein (HS-ACP) picks up
an acetyl group from acetyl CoA.CH3C-SCoA
O
+ HS-ACP
+ HS-synthase
+ HS-synthase
CH3C-S-ACP
O
CH3C-SCoA
O
CH3C-S-ACP
O
CH3C-S-synthase
O
CH3C-S-Synthase
O
+ HS-CoA
+
+ HS-ACP
HS-CoA
Acetyl-CoA Acetyl-ACP
Acetyl-ACP Acetyl-synthase
Acetyl-synthaseAcetyl-CoA
14. Fatty Acid Biosynthesis
– Step 2: The condensation step: the C3 fragment on the
synthase is now condensed with a C2 fragment in a reaction
that gives off CO2.
– Step 3: The resulting 4-carbon fragment then undergoes three
consecutive reactions: reduction, dehydration, and reduction
to give a fully saturated C4 fragment. These three reactions are
shown on the next two screens. As you study them, note that
they are the reverse of three steps in the b-oxidation of fatty
acids.
16. Fatty Acid Biosynthesis
• Step 6: the second reduction:
O
H
C C
C-S-ACP
H3C H
+ NADPH + H+
CH3-CH2-CH2-C-S-ACP
O
+ NADP+
Butyryl-ACP
Crotonyl-ACP
17. Fatty Acid Biosynthesis
– The cycle now repeats on butyryl-ACP.CH3CH2CH2C-S-ACP
O
+ CH2C-S-ACP
CO2
-
O
CH3CH2CH2CH2CH2C-S-ACP
O
Malonyl-ACP
Butyryl-ACP
Hexanoyl-ACP
3. condensation
4. reduction
6. reduction
5. dehydration
18. Fatty Acid Biosynthesis
– Higher fatty acids, for example C18 (stearic acid),
are obtained by addition of one or more
additional C2 fragments by a different enzyme
system.
– Unsaturated fatty acids are synthesized from
saturated fatty acids by enzyme-catalyzed
oxidation at the appropriate point on the
hydrocarbon chain.
– The structure of NADP+ is the same as NAD+
except that there is an additional phosphate
group on carbon 3’ of one of the ribose units.
19. Membrane Lipids
The two building blocks for the synthesis of
membrane lipids are:
– Activated fatty acids in the form of their acyl CoA
derivatives.
– Glycerol 1-phosphate, which is obtained by
reduction of dihydroxyacetone phosphate (from
glycolysis):
CH2-OH
C=O
CH2-OPO3
2-
NADH + H+
CH2-OH
CH
CH2-OPO3
2-
HO NAD+
Dihydroxyacetone
phosphate
Glycerol
1-phosphate
+ +
20. Membrane Lipids
– Glycerol 1-phosphate combines with two acyl
CoA molecules, which may be the same or
different:
– To complete the synthesis of a phospholipid, an
activated serine, choline, or ethanolamine is
added to the phosphatidate by formation of a
CH2-OH
CH
CH2-OPO3
2-
HO 2RC-S-CoA
O CH2-OCR
CH
CH2-OPO3
2-
RCO
O
O
2CoA-SH+ +
Acyl CoA A phosphatidateGlycerol
1-phosphate
21. Cholesterol
All carbon atoms of cholesterol and of all
steroids synthesized from it are derived from
the two-carbon acetyl group of acetyl CoA.
• Synthesis starts with reaction of three molecules
of acetyl CoA to form the six-carbon compound
3-hydroxy-3-methylglutaryl CoA (HMG-CoA).
• The enzyme HMG-CoA reductase then catalyzes
the reduction of the thioester group to a primary
alcohol.
22. Cholesterol
– In a series of steps requiring ATP, mevalonate
undergoes phosporylation and decarboxylation
to give the C5 compound, isopentenyl
pyrophosphate.
– This compound is a key building block for all
steroids and bile acids.
24. Amino Acids
Most nonessential amino acids are
synthesized from intermediates of either
glycolysis or the citric acid cycle.
• Glutamate, for example, is synthesized by
amination and reduction of a-ketoglutarate, a
citric acid cycle intermediate:
25. Amino Acids
• Glutamate in turn serves as an intermediate
in the synthesis of several amino acids by the
transfer of its amino group by
transamination.
26. Amino Acids
• Figure 29.6
A summary
of
anabolism
showing the
role of the
central
metabolic
pathway.
