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Chemistry 203
Chapter 24
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 + Glucose 1-phosphate
Glycogen
(one unit smaller)
(Glucose)n-1 + UDP-glucose
(Glucos e)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
Glycolysis
Glucose is converted to two molecules of pyruvate.
An anaerobic reaction in cytoplasm.
10 Reactions
Glycolysis
Steps [1] – [5] energy investment phase:
2 ATP molecules are hydrolyzed.
The 6-carbon glucose molecule is converted into two 3-carbon segments.
Glycolysis
Steps [6] – [10] energy-generating phase:
producing 1 NADH and 2 ATPs for each pyruvate formed.
Glycolysis
Enzymes:
Glycolysis
Step [1] begins with the
phosphorylation of glucose
into glucose 6-phosphate,
using an ATP and a kinase
enzyme.
Glycolysis
Step [2] isomerizes
glucose 6-phosphate to
fructose 6-phosphate
with an isomerase enzyme.
Glycolysis
Step [3] is the
phosphorylation of
fructose 6-phosphate into
fructose 1,6-bisphosphate
with a kinase enzyme.
Glycolysis
Overall, the first three steps of glycolysis:
1. 2 phosphate groups is added.
2. A 6-membered glucose ring is isomerized
into a 5-membered fructose ring.
3.
The energy stored in 2 ATP molecules is utilized to
modify the structure of glucose
Glycolysis
Step [4] cleaves the fructose ring into a dihydroxy-acetone phosphate
and a glyceraldehyde 3-phosphate.
Glycolysis
Step [5] isomerizes the dihydroxyacetone phosphate
into another glyceraldehyde 3-phosphate.
Thus, the first phase of glycolysis converts glucose into
2 glyceraldehyde 3-phosphate units and 2 ATP is used.
Glycolysis
In step [6] the aldehyde end of the molecule is oxidized and
phosphorylated by a dehydrogenase enzyme and NAD+;
this produces 1,3-bisphospho-glycerate and NADH.
Glycolysis
In step [7], the phosphate group is transferred onto an ADP with
a kinase enzyme, forming 3-phosphoglycerate and ATP.
Glycolysis
In step [8], the phosphate group is isomerized to
a new position in 2-phosphoglycerate.
Glycolysis
In step [9], water is lost to form phosphoenol-pyruvate.
Glycolysis
In step [10], the phosphate is transferred to an ADP,
yielding pyruvate and ATP with a kinase enzyme.
Glycolysis
The 2 glyceraldehyde 3-phosphate units are converted into
2 pyruvate units in phase two of glycolysis.
Overall, the energy-generating phase forms 2 NADHs
and 4 ATPs.
Glycolysis
2 ATPs are used in phase one of glycolysis, and 4 ATPs are made in
phase two of glycolysis.
The net result is the synthesis of 2 ATPs from glycolysis.
The 2 NADHs formed are made in the cytoplasm and must be
transported to the mitochondria to join the electron transport chain
and make ATP.
Overall of glycolysis
The fate of pyruvate
under aerobic
conditions
under anaerobic
conditions
in fermentation
by microorganisms
Aerobic conditions
Pyruvate must diffuse across the outer and inner membrane of
mitochondria into the matrix.
The NADH formed needs O2 to return to NAD+, so without O2 no
additional pyruvate can be oxidized.
Fermentation
Fermentation is the anaerobic conversion of glucose to
ethanol and CO2 by yeast and other microorganisms.
1. Biosynthesis of Carbohydrates
In plants
chloroph yll
6 H2 O
6
H
O
energy
6CO
+
+
2
2
(from
(fromsun)
su n ligh t)
Photosynthesis
C6 H1 2 O6 + 6 H2 O
Glu cose
1. Biosynthesis of Carbohydrates
In animals
When both glucose and stored glycogen are depleted, glucose can
be synthesis by gluconeogenesis.
(in liver)
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.
Gluconeogenesis
Glucose is the main source of energy for cells and the only source of
energy used by the brain.
Gluconeogenesis is a mechanism that ensures that the brain has
a supply of glucose when a diet is low in carbohydrates.
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
CH2 OH
O
H
H
OH
HO
H
O
H
O O
O-P-O-P-OCH2
O O
OH
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
CH2 OH CH2 OH
O
O H
HO H
H
HN
HN
H
H
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
OH
OH
HO
HO
CH2 OH CH2 OH
O
date
iphosph
ate glu cose
Uridine O
dUridine
iphosph
glu
O
H cose
H
(Glucose)nH H H(UD
HN
(UD P-glucose) HN
HP-glucose)
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
CH3 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:
H
H3 C
OH
C
O
CH2 -C- S- ACP
D--Hydroxybutyryl-ACP
O
C-S-A CP
H
C C
H3 C
H
Crotonyl-ACP
+ H2 O
2. Biosynthesis of Fatty acids
Step 6: the second reduction:
O
H
C-S-A CP
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 CH 2 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 CH2 CH 2 CH 2 CH2 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 Isopentenyl
pyrophos phate
Is oprene
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 pyrophos phate
OP2 O6 3 Farnesyl pyrophos phate
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- C- CH2 - CH 2 - C-COO - + N H4
O
-Ketoglutarate
N AD P+
O
-
N H3 +
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.
COOCOOC= O + CH- NH3 +
CH3
CH2
CH2
COOPyruvate
Glutamate
COOCH- NH3 + +
CH3
Alanine
COOC= O
CH2
CH2
COO-Ketoglutarate