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Biosynthetic Pathways: Frederick A. Bettelheim William H. Brown Mary K. Campbell Shawn O. Farrell
Biosynthetic Pathways: Frederick A. Bettelheim William H. Brown Mary K. Campbell Shawn O. Farrell
Bettelheim
William H. Brown
Mary K. Campbell
Shawn O. Farrell
www.cengage.com/chemistry/bettelheim
Chapter 29
Biosynthetic Pathways
29-2
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:
29-3
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.
chlorophyll
6 H2 O + 6 H2 O + energy C6 H1 2 O6 + 6 H2 O
(from Glucose
sun light)
29-4
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.
29-5
Synthesis of Glucose
Figure 29.1 Gluconeogenesis.
29-6
Synthesis of Glucose
Figure 29.1 Gluconeogenesis (continued)
29-7
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 .
CH2 OH O
H O H
H HN
OH H O O
HO O-P-O-P-OCH2 O N
O- O- O
H OH H H
H H
HO OH
Uridine diphosphate glucose
(UDP-glucose)
29-8
Other Carbohydrates
• glycogenesis: The synthesis of glycogen from glucose.
Glucose 1-phosphate + UTP UDP-glucose + pyrophosphate
(Glucose)n + UDP-glucose (Glucose)n+ 1 + UDP
29-9
The Cori Cycle
Figure 29.2
Lactate from
glycolysis in
muscle is
transported to
the liver, where
gluconeogensis
converts it back
to glucose.
29-10
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 -
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.
29-11
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).
29-12
Fatty Acid Biosynthesis
Step 1: Priming of the system by acetyl-CoA.
O O
CH3 C-S Co A + HS -ACP CH3 C-S-ACP + HS -CoA
Acetyl-CoA Acetyl-ACP
O O
CH3 C-S-ACP + HS -s ynthase CH3 C-S-Synthase + HS -ACP
Acetyl-ACP Acetyl-synthase
O O
CH3 C-S Co A + HS -s ynthase CH3 C-S-synthase + HS -CoA
Acetyl-CoA Acetyl-synthase
29-13
Fatty Acid Biosynthesis
• Step 2: ACP-malonyltransferase reaction:
O O
CH2 C-S CoA + HS-ACP CH2 C-S-ACP + HS-CoA
COO- COO-
Malonyl-CoA Malonyl-ACP
• Step 5: Dehydration:D--Hydroxybutyryl-ACP
OH O
C O H C-S -A CP
H CH2 -C- S - ACP C C + H2 O
H3 C
H3 C H
D--Hydroxybutyryl-ACP Crotonyl-ACP
29-15
Fatty Acid Biosynthesis
• Step 6: the second reduction:
O
H C-S -A CP
C C + N AD PH + H+
H3 C H
Crotonyl-ACP O
CH3 -CH 2 - CH2 -C- S - ACP + N AD P +
Butyryl-ACP
29-16
Fatty Acid Biosynthesis
• The cycle now repeats on butyryl-ACP.
O O
CH3 CH2 CH2 C-S - ACP + CH2 C-S -A CP
Butyryl-ACP CO 2 -
Malonyl-ACP
3. condensation
4. reduction
5. dehydration
6. reduction
O
CH3 CH2 CH2 CH2 CH2 C- S - ACP
Hexanoyl-ACP
R (CH2 ) n COOH
C C + 2 H2 O + NADP+
H H
29-18
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 CH2 -OH
C=O + NADH + H+ HO CH + NAD+
CH2 -OPO3 2 - CH2 -OPO3 2 -
Dihydroxyacetone Glycerol
phosphate 1-phosphate
29-19
Membrane Lipids
• Glycerol 1-phosphate combines with two acyl CoA
molecules, which may be the same or different:
O
CH2 -OH O O CH2 -OCR
HO CH + 2 RC-S-CoA RCO CH + 2 CoA-SH
CH2 -OPO3 2 - CH2 -OPO3 2 -
Glycerol Acyl CoA A phosphatidate
1-phosphate
O OH O HMG-CoA O OH
O
reductase
3 CH3 CS CoA -
O SCoA -
O OH
Acetyl CoA 3-Hydroxy-3- Mevalonate
methylglutaryl-CoA
29-21
Cholesterol
• In a series of steps requiring ATP, mevalonate
undergoes phosporylation and decarboxylation to give
the C5 compound, isopentenyl pyrophosphate.
• This compound has the carbon skeleton of isoprene,
and is a key building block for all terpenes (Section
12.5) and steroids.
O OH
- 3-
O OH OP2 O6
Mevalonate Isopentenyl Isoprene
pyrophosphate
29-22
Cholesterol
• Isopentenyl pyrophosphate (C5) is the building block
for the synthesis of geranyl pyrophosphate (C10) and
farnesyl pyrophosphate (C15).
• In these structural formulas, the bonds joining
isoprene units are shown in red.
OP2 O6 3 - OP2 O6 3 -
Geranyl pyrophosphate Farnesyl pyrophosphate
29-23
Cholesterol
• Two farnesyl pyrophosphate (C15) units are joined to
form squalene (C30) and, in a series of at least 25 steps,
squalene is converted to cholesterol (C30).
Cholesterol
HO
29-25
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.
COO- COO- COO- COO-
C= O + CH- NH3 + CH- NH3 + + C= O
CH3 CH2 CH3 CH2
CH2 CH2
COO- COO-
Pyruvate Glutamate Alanine -Ketoglutarate
29-26
Amino Acids
-Ketoglutarate Oxaloacetate Pyruvate
Glutamate Aspartate Valine
Glutamine Asparagine Alanine
Proline Methionine Leucine
Arginine Threonine
Isoleucine
Lysine
Phosphoenolpyruvate +
3-Phosphoglycerate Erythrose 4-phosphate
Serine Phenylalanine
Cysteine Tyrosine
Glycine Tryptophan
Ribose 5-phosphate
Histidine
29-27
Chapter 29 Biosynthetic Pathways
End
Chapter 29
29-28