Chemistry 20
Chapter 21
Biosynthetic Pathways
Metabolism
Catabolic reactions:
Complex molecules  Simple molecules + Energy
Anabolic reactions:
Biosynthetic reactions
Simple molecules + Energy (in cell)  Complex molecules
Biosynthetic pathways
Anabolic and catabolic reactions have different pathways.
1. Flexibility: if a normal biosynthetic pathway is blocked, the organism can
often use the reverse of the catabolic pathway for synthesis.
Catabolic
Simple Molecules
Complex Molecule
Biosynthetic
Biosynthetic pathways
2. Overcoming Le Chatelier’s principle:
If a dynamic equilibrium is disturbed by changing the conditions,
the position of equilibrium moves to counteract the change.
(Glucose)n + Pi
Glycogen
phosphorylase
(Glucos e)n-1 + Glu cose 1-ph osp hate
Glycogen
(one un it smaller)
(Glucose)n-1 + UDP-glucose
(Glucose)n + UDP
Glycogen
(one unit larger)
Biosynthetic pathways
Anabolic and catabolic reactions need different energy.
Anabolic and catabolic reactions take place in different locations.
Catabolic reactions
Mitochondria
Anabolic reactions
Cytoplasm
Biosynthetic pathways
1. Biosynthesis of Carbohydrates
Biosynthesis of Fatty acids
2. Biosynthesis of Lipids
Biosynthesis of Membrane Lipids
3. Biosynthesis of Amino acids
1. Biosynthesis of Carbohydrates
In plants
chloroph yll
6 H2 O
6
H
O
energy
6CO
+
+
2
2
(from sun)
(from
su n ligh t)
Photosynthesis
C6 H1 2 O6 + 6 H2 O
Glu cose
1. Biosynthesis of Carbohydrates
In animals
When energy is not needed, glucose can be synthesis by gluconeogenesis.
Intermediates of Glycolysis and Citric acid cycle are used to produce glucose.
Gluconeogenesis is not the exact reversal of glycolysis:
pyruvate to glucose does not occur by reversing the steps of glucose to pyruvate.
1. Biosynthesis of Carbohydrates
Only four enzymes are unique.
(compare to glycolysis)
ATP is produced in glycolysis
and used up in gluconeogenesis.
Cori Cycle
Lactate from glycolysis in muscle is transported to the liver,
where gluconeogenesis converts it back to glucose.
Conversion of glucose to other Carbohydrates (in animals)
Conversion of glucose to other hexoses (isomers) and synthesis of
di- or polysaccharides.
Activation of glucose by Uridine Triphosphate (UTP) to form UDP-glucose.
(Similar to ATP)
H
CH 2 OH
O
H
H
OH
HO
H
O
H
O O
O-P-O-P-OCH2
O- OOH
H
HN
O
O
H
HO
Uridine d iphosph ate glu cose
(UD P-glucose)
N
H
H
OH
Conversion of glucose to other Carbohydrates (in animals)
Glycogenesis: conversion of glucose to glycogen.
Exess glucose is stored in form of glycogen.
Glu cose 1-ph osp hate + UTP
(Glucose)n + UD P-glucose
Glu cose 1-ph osp hate + UTP +
O
CH 2 OH CH 2 OH
O
O H
HO HH
H H
HN
HN
O
O
O
O
H H OH
OH
Enzyme
O
N
O- hate
O-P-O-P-OCH
O-P-O-P-OCH
HO
HO UD P-glucose
2N
2
pyrophosp
+ O
O
O OH O
H
OHH O OH
H
HH
(Glucos e)n+1 + UDHP
H H
H
OH
OH
HO
HO
CH 2 OH CH 2 OH
O
d
iphosph
ate
glu
cose
Uridine O
dUridine
iphosph
ate
glu
cose
O H
H
(Glucose)nH H H(UDHP-glucose)
HN
(UD P-glucose) HN
O
O
O
O
H H OH
OH
O
O- hate
O-P-O-P-OCH
(Glucos
P + pyrophosp
HO e)n+1HO
+ UDO-P-O-P-OCH
2N
2
O
O
O OH O
H
OHH O OH
H
HH
Same process to produce di- and
H H
H
OH
HO
HO
iphosph
ate glu cose
Uridine
dUridine
iphosphdate
glu cose
polysaccharides.
(UD P-glucose)
(UD P-glucose)
O
2. Biosynthesis of Fatty acids
Our body can produce all the fatty acids except essential fatty acids.
Acetyl CoA
They build up two C at a time.
Fatty acids synthesis: in cytoplasm
Degeradation of fatty acids: in mitochondria
Excess food
Acetyl CoA
Fatty acids
Lipid (fat)
2. Biosynthesis of Fatty acids
Acyl Carrier Protein (ACP)
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).
At each enzyme, one reaction of chain is catalyzed.
2. Biosynthesis of Fatty acids
Step 1: ACP picks up an acetyl group from acetyl CoA and delivers to the first enzyme:
O
CH3 C-SCoA + HS-ACP
A cetyl-CoA
O
CH3 C-S-ACP + HS-CoA
Acetyl-ACP
O
CH 3 C-S-ACP + HS-synth ase
Acetyl-ACP
O
CH3 C-S-Synthas e + HS-ACP
Acetyl-synthase
O
CH3 C-SCoA + HS-synth ase
A cetyl-CoA
O
CH3 C-S-synthas e + HS-CoA
Acetyl-synthase
2. Biosynthesis of Fatty acids
Step 2: ACP-malonyltransferase reaction:
O
CH2 C-SCoA + HS-ACP
COOMalonyl-CoA
O
CH2 C-S-ACP + HS-CoA
COOMalonyl-ACP
Step 3: condensation reaction:
O
O
CH3 C-S-synth ase + CH2 C-A CP
COOAcetyl-synthase
Malonyl-ACP
O
O
CH3 C-CH2 - C-S- A CP + CO 2 + HS-synth ase
Acetoacetyl-ACP
2. Biosynthesis of Fatty acids
Step 4: the first reduction:
O
O
CH3 C-CH2 - C-S- A CP + N AD PH + H+
Acetoacetyl-ACP
OH
H
H3 C
C
O
CH2 -C- S- ACP + N AD P+
D--Hydroxybutyryl-ACP
Step 5: dehydration:
O
C-S-A CP
OH
H
H3 C
C
O
CH2 -C- S- ACP
D--Hydroxybutyryl-ACP
H
+ H2 O
C C
H3 C
H
Crotonyl-ACP
2. Biosynthesis of Fatty acids
Step 6: the second reduction:
O
C-S-A CP
H
C
H3 C
C
H
Crotonyl-ACP
+ N AD PH + H+
O
CH3 -CH 2 - CH2 -C- S- ACP + N AD P+
Butyryl-ACP
One cycle of merry-go-round.
2. Biosynthesis of Fatty acids
Second cycle:
O
O
CH 3 CH2 CH2 C-S- ACP + CH 2 C-S-A CP
Butyryl-ACP
CO 2 Malonyl-ACP
3.
4.
5.
6.
condens ation
reduction
dehydration
reduction
O
CH3 CH 2 CH2 CH2 CH 2 C- S- ACP
Hexanoyl-ACP
Maximum 16C (Palmitic acid). For 18C (Stearic acid) another system and enzyme.
3. Biosynthesis of Membrane Lipids
1- Glycerophospholipid
2- Cholesterol
3. Biosynthesis of Membrane Lipids
Glycerol 1-phosphate, which is obtained by reduction of
dihydroxyacetone phosphate (from glycolysis).
CH2 -OH
+ NADH + H+
C=O
2CH2 -OPO3
D ihydroxyaceton e
ph osp hate
CH2 -OH
+ NAD+
HO CH
2CH2 -OPO3
Glycerol
1-p hosphate
A vehicle for transporting electrons in and out of mitochondria.
3. Biosynthesis of Membrane Lipids
Fatty acids are activated by CoA, forming Fatty Acyl CoA.
CH2 -OH
O
+ 2 RC-S-CoA
HO CH
CH2 -OPO3 2 Glycerol
Acyl CoA
1-phosp hate
O
CH2 -OCR
O
+ 2 CoA-SH
RCO CH
CH2 -OPO3 2 A phosp hatidate
An amino alcohol is added to phosphate by phosphate ester bond.
Is activated by CTP (like UTP but cytosine instead of uracil)
3. Biosynthesis of Membrane Lipids
Cholesterol is made of acetyl CoA (all of the C atoms).
In Liver
First reaction of three acetyl CoA to form the six-carbon compound
3-hydroxy-3-methylglutaryl CoA (HMG-CoA).
O
3 CH3 CSCoA
Acetyl CoA
O
-2CoA-SH
-
O
OH O
SCoA
3-Hyd roxy-3methylglutaryl-CoA
HMG-CoA
reductase
-1CoA-SH
O
-
OH
O
OH
Mevalonate
3. Biosynthesis of Membrane Lipids
Mevalonate undergoes phosporylation and decarboxylation
to give the C5 compound, isopentenyl pyrophosphate.
O
-
OH
O
ATP  ADP
OH
Mevalonate
-CO2
OP2 O6 3 Isopen tenyl
pyroph os phate
Is op ren e
Building block
3. Biosynthesis of Membrane Lipids
Isopentenyl pyrophosphate (C5) is the building block for the synthesis of
geranyl pyrophosphate (C10) and farnesyl pyrophosphate (C15).
OP2 O6 3 Geranyl pyroph os phate
OP2 O6 3 Farnesyl pyrophos ph ate
3. Biosynthesis of Membrane Lipids
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 (C27).
Cholesterol
HO
4. Biosynthesis of Amino Acids
All 20 amino acids are found in a normal diet.
Essential amino acids: cannot be synthesis in our body.
Nonessential amino acids: can be synthesis in our body.
4. Biosynthesis of Amino Acids
Most nonessential amino acids are synthesized from
intermediates of either glycolysis or the citric acid cycle.
N AD PH + H+
O
O
O- C- CH2 - CH 2 - C-COO - + N H4 +
-Ketoglutarate
N AD P+
+
N H3
O
O- C- CH2 - CH 2 - CH- COO Glutamate
Amination and reduction
Reverse of oxidative deamination reaction (degradation in catabolism).
4. Biosynthesis of 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.
COOC= O
CH3
COO+ CH- NH3 +
CH2
CH2
COOPyruvate
Glutamate
COOCH- NH3 + +
CH3
Alanine
COOC= O
CH2
CH2
COO-Ketoglutarate