Chapter 21 Biosynthetic Pathways

Chapter 21

Biosynthetic Pathways

Chemistry 20

Catabolic reactions:

Anabolic reactions: Biosynthetic reactions

Complex molecules Simple molecules + Energy

Simple molecules + Energy (in cell) Complex molecules

Metabolism

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.

Complex Molecule Simple MoleculesCatabolic

Biosynthetic

(Glucose)n +Pi

Glycogen

phosphorylase(Glucose)n-1

Glycogen(one unit smaller)

+Glucose 1-phosphate

(Glucose)n-1 +UDP-glucose (Glucose)nGlycogen

(one unit larger)

+ UDP

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.


Anabolic and catabolic reactions need different energy.

Anabolic and catabolic reactions take place in different locations.

Catabolic reactions

Anabolic reactions

Mitochondria

Cytoplasm


1. Biosynthesis of Carbohydrates

2. Biosynthesis of Lipids

Biosynthesis of Fatty acids

Biosynthesis of Membrane Lipids

3. Biosynthesis of Amino acids


6H2O 6H2O C6H12O6 6H2O+ +energy chlorophyll +(from

sun light)Glucose(from sun)

In plants

6CO2

Photosynthesis


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.


Only four enzymes are unique.

(compare to glycolysis)

ATP is produced in glycolysis and used up in gluconeogenesis.

Lactate from glycolysis in muscle is transported to the liver,

where gluconeogenesis converts it back to glucose.

Cori Cycle

Conversion of glucose to other Carbohydrates (in animals)

Conversion of glucose to other hexoses (isomers) and synthesis ofdi- or polysaccharides.

Activation of glucose by Uridine Triphosphate (UTP) to form UDP-glucose.

OH

HO

H

O-P-O-P-OCH2

H

OHH

OH

CH2OH

H

O-

O

O-

O

HHHO OH

H HO

HN

N

O

O

Uridine diphosphate glucose (UDP-glucose)

(Similar to ATP)

UTP

UTP

UDP

UDP

pyrophosphate

pyrophosphate

Glucose 1-phosphate + UDP-glucose +

(Glucose)n +UDP-glucose (Glucose)n+1 +

Glucose 1-phosphate + + (Glucose)n

(Glucose)n+1 + +

OH

HO

H

O-P-O-P-OCH2

H

OHH

OH

CH2OH

H

O-

O

O-

O

HHHO OH

H HO

HN

N

O

O


OH

HO

H

O-P-O-P-OCH2

H

OHH

OH

CH2OH

H

O-

O

O-

O

HHHO OH

H HO

HN

N

O

O


- -

OH

HO

H

O-P-O-P-OCH2

H

OHH

OH

CH2OH

H

O-

O

O-

O

HHHO OH

H HO

HN

N

O

O


OH

HO

H

O-P-O-P-OCH2

H

OHH

OH

CH2OH

H

O-

O

O-

O

HHHO OH

H HO

HN

N

O

O


- -

Enzyme

Conversion of glucose to other Carbohydrates (in animals)

Glycogenesis: conversion of glucose to glycogen.

Exess glucose is stored in form of glycogen.

Same process to produce di- and polysaccharides.

2. Biosynthesis of Fatty acids

Our body can produce all the fatty acids except essential fatty acids.

Acetyl CoA

Fatty acids synthesis: in cytoplasm

Degeradation of fatty acids: in mitochondria

They build up two C at a time.

Excess food Acetyl CoA Fatty acids Lipid (fat)


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).

Acyl Carrier Protein (ACP)

At each enzyme, one reaction of chain is catalyzed.

CH3C-SCoAO

+ HS-ACP

+ HS-synthase

+ HS-synthase

CH3C-S-ACPO

CH3C-SCoAO

CH3C-S-ACPO

CH3C-S-synthaseO

CH3C-S-SynthaseO

+ HS-CoA

+

+ HS-ACP

HS-CoA

Acetyl-CoA Acetyl-ACP

Acetyl-ACP Acetyl-synthase

Acetyl-synthaseAcetyl-CoA


Step 1: ACP picks up an acetyl group from acetyl CoA and delivers to the first enzyme:


Step 2: ACP-malonyltransferase reaction:

Step 3: condensation reaction:

CH2C-SCoA

COO-

O+ HS-ACP CH2C-S-ACP

COO-

O+ HS-CoA

Malonyl-CoA Malonyl-ACP

CH3C-S-synthaseO

+ CH2C-ACPCOO-

O

CH3C-CH2-C-S-ACPO O

+ CO2 + HS-synthase

Acetyl-synthaseMalonyl-ACP

Acetoacetyl-ACP

Step 4: the first reduction:

Step 5: dehydration:


CH3C-CH2-C-S-ACP

O

Acetoacetyl-ACP

+ NADPH + H+

D--Hydroxybutyryl-ACP

C

OH

CH2-C-S-ACPHH3C

O+ NADP+

O

D--Hydroxybutyryl-ACP

OH

C CC-S-ACP

H3C H

+ H2O

Crotonyl-ACP

C

OH

CH2-C-S-ACPHH3C

O

CH3-CH2-CH2-C-S-ACP

O

Butyryl-ACP

+ NADPH + H+

OH

C C

C-S-ACP

H3C HCrotonyl-ACP

+ NADP+

Step 6: the second reduction:


One cycle of merry-go-round.

Maximum 16C (Palmitic acid). For 18C (Stearic acid) another system and enzyme.

+ CH2C-S-ACPCO2

-

Malonyl-ACP

CH3CH2CH2C-S-ACPO

CH3CH2CH2CH2CH2C-S-ACP

Butyryl-ACP

Hexanoyl-ACP

3. condensation4. reduction

6. reduction5. dehydration

O

O


Second cycle:

3. Biosynthesis of Membrane Lipids

1- Glycerophospholipid

2- Cholesterol


Glycerol 1-phosphate, which is obtained by reduction of

dihydroxyacetone phosphate (from glycolysis).

CH2-OHC=OCH2-OPO3

2-NADH + H+

CH2-OHCHCH2-OPO3

2-HO NAD+

Dihydroxyacetonephosphate

Glycerol1-phosphate

+ +

A vehicle for transporting electrons in and out of mitochondria.


CH2-OHCHCH2-OPO3

2-HO 2RC-S-CoA

O CH2-OCR

CH

CH2-OPO32-

RCOO

O

2CoA-SH+ +

Acyl CoA A phosphatidateGlycerol1-phosphate

Fatty acids are activated by CoA, forming Fatty Acyl CoA.

An amino alcohol is added to phosphate by phosphate ester bond.

Is activated by CTP (like UTP but cytosine instead of uracil)


Cholesterol is made of acetyl CoA (all of the C atoms).

3CH3CSCoAO

-O SCoA

OO OH

Acetyl CoA 3-Hydroxy-3-methylglutaryl-CoA

-O OH

O OH

Mevalonate

HMG-CoAreductase

First reaction of three acetyl CoA to form the six-carbon compound

3-hydroxy-3-methylglutaryl CoA (HMG-CoA).

-2CoA-SH

-1CoA-SH

In Liver

Mevalonate undergoes phosporylation and decarboxylation to give the C5 compound, isopentenyl pyrophosphate.


-CO2

ATP ADP-O OH

O OH

MevalonateOP2O6

3-

Isopentenylpyrophosphate

Isoprene

Building block

Isopentenyl pyrophosphate (C5) is the building block for the synthesis of

geranyl pyrophosphate (C10) and farnesyl pyrophosphate (C15).


OP2O63-

OP2O63-

Geranyl pyrophosphate Farnesyl pyrophosphate


HOCholesterol

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).

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.

Most nonessential amino acids are synthesized from

intermediates of either glycolysis or the citric acid cycle.


-O-C-CH2-CH2-C-COO-

-Ketoglutarate

+ NH4+

-O-C-CH2-CH2-CH-COO-

NH3+

Glutamate

NADPH + H+

NADP+

O

O O

Amination and reduction

Reverse of oxidative deamination reaction (degradation in catabolism).


Glutamate in turn serves as an intermediate in the synthesis of

several amino acids by the transfer of its amino group by transamination.

COO-

C=OCH3

COO-

CH-NH3+

CH2CH2COO-

COO-

CH-NH3+

CH3

COO-

C=OCH2CH2COO-

-KetoglutaratePyruvate

+

AlanineGlutamate

+

Chapter 21 Biosynthetic Pathways

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