Download Chapter 21 Biosynthetic Pathways

Chapter 21
Biosynthetic Pathways
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:
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.
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.
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.
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.
The Cori Cycle
Figure 21.2 The
Cori cycle.
Lactate from
glycolysis in
muscle is
transported to the
liver, where
gluconeogensis
converts it back to
glucose.
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.
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).
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.
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
+ NADH + H+
2CH2 -OPO3
Dihydroxyacetone
phosphate
CH2 -OH
HO CH
+ NAD+
2CH2 -OPO3
Glycerol
1-phosphate
Membrane Lipids
• Glycerol 1-phosphate combines with two acyl CoA molecules,
which may be the same or different:
CH2 -OH
O
+ 2RC-S-CoA
HO CH
CH2 -OPO3 2Glycerol
Acyl CoA
1-phosphate
O
CH2 -OCR
O
+ 2CoA-SH
RCO CH
CH2 -OPO3 2A phosphatidate
• To complete the synthesis of a phospholipid, an activated serine,
choline, or ethanolamine is added to the phosphatidate by
formation of a phosphoric ester.
• Sphingolipids and glycolipids are assembled in similar fashion
from the appropriate building blocks.
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.
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.
Cholesterol
• Isopentenyl pyrophosphate (C5) is the building block for the
synthesis of geranyl pyrophosphate (C10) and farnesyl
pyrophosphate (C15).
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:
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.
Amino Acids
•
Figure 21.6 A
summary of
anabolism
showing the role
of the central
metabolic
pathway.