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Anabolic Pathway (Biosynthetic Pathway) Introduction

Anabolism - Pathway of anabolism is different from


- Synthesis of larger molecule from catabolism
smaller molecule 1. Anabolism has Flexibility
- Excess smaller molecule in metabolism - Normal biosynthetic pathway is blocked,
will be used to synthesize larger the organism can often use reverse of
molecule to be used for storage the degradation pathway for synthesis.
- Happens in starvation, conversion of - If the catabolism are usually block via
larger molecules to smaller molecule enzymes, excess molecules will undergo
synthesis
Different larger molecules in the catabolic 2. Overcoming Le Chatelier’s principle
pathway for energy - Reactant with higher concentration
1. Carbohydrates leads to forward reaction
- Break down to monosaccharide to - Product with higher concentration leads
undergo glycolysis to reverse reaction
- to produce pyruvate to become Acetyl - Enzyme phosphorylase can perform
Co-enzyme A for the citric acid cycle forward and reverse reaction, it can
- NADH and FADH2 will go to the oxidative overcome the Le Chatelier’s principle
phosphorylation in the ETC to produce - Large excess of phosphate would drive
chemical energy in the ATP. the reaction to the right, driving the
2. Lipids hydrolysis of glycogen
- Source if there is scarce carbohydrate - To provide an alternative pathway for
supply the synthesis of glycogen, even in the
- Glycerol will undergo glycolysis presence of excess phosphate
- Fatty acids coming from sphingolipids - Use UDP-glucose to further synthesize a
will undergo beta oxidation larger molecule of glycogen
- Final product will be Acetyl CoA for the
citric acid cycle Carbohydrate Biosynthesis
3. Proteins - Conversion of carbon dioxide to glucose
- Broken down to amino acid in plants
- Before entering pyruvate in Acetyl CoA, - Synthesis of glucose in animals and
oxidative deamination will occur to humans
remove nitrogen in amino acid. - Conversion of glucose to other forms of
- After that ammonia will be produced carbohydrates
which will undergo the urea cycle. - Photosynthesis takes place in plants
Anabolism - Carbon dioxide and water in the
- Only one mole of Acetyl CoA will presence of sunlight (energy) happens
undergo citric acid cycle inside the chlorophyll and produces
- Cannot be a simultaneous process glucose and oxygen.
- Acetyl will need one mole of
oxaloacetate to undergo citric acid cycle Gluconeogenesis
- Excess of Acetyl co enzyme A and - Synthesis of Glucose from a non-
undergo anabolism carbohydrate source (lipids or
- May be produced as lipids or aminoacids)
carbohydrates - Creation of new glucose (neogenesis)
- Sometimes proteins but lipids and - These sources are most commonly
carbohydrates are more favorable pyruvate, citric acid cycle intermediates,
and glucogenic amino acids.
- Gluconeogenesis is not the exact uridine diphosphate glucose (UDP-
reversal of glycolysis glucose) + Pi
Steps omitted in glycolysis:
- pyruvate to glucose does not occur by
reversing the steps of glucose to
pyruvate.
- There are three irreversible steps in
glycolysis:
a. Phosphoenolpyruvate + ADP to Glycogenesis
form pyruvate and ATP - Synthesis of glycogen from glucose.
b. Fructose 6 phosphate to
fructose 1,6 bisphosphate.
c. Glucose to glucose 6 phosphate.
- These three steps are reversed in
gluconeogenesis, but by different
reactions and using different enzymes. - The biosynthesis of other di-, oligo-,
and polysaccharides also uses this
common activation step to form an
appropriate UDP derivative.
- Utilize UTP to form UDP
- Every time this occurs, the chain of
hydrogen becomes longer

Cori Cycle

Happens in the mitochondria you can form


pyruvate where pyruvate can come from citric
acid, lactate and glucogenic amino acid
- Oxaloacetate will become a phophoenol
pyruvate by a 5-step reaction.
- The five steps will form Fructose 1,6-
bisphosphate, Fructose 6-phosphate,
Glucose 6-phosphate and Glucose.
- Involves enzyme that catalyze
gluconeogenesis only.

Other Carbohydrates - Lactate from glycolysis in muscle is


- Glucose is converted to other hexoses transported to the liver, where
and to disaccharide, oligosaccharide, gluconeogensis converts it back to
and polysaccharide glucose
- The common step in all of these - Glucose will be transported from liver to
syntheses is activation of glucose by muscle via blood (RBC)
uridine triphosphate (UTP) to form
- Glycolysis to form pyruvate, which will - Acety CoA will react with acyl carrier
form co enzyme A and undergo Citric protein to produce an acetyl ACP
acid cycle. complex and the byproduct is CoAsh that
- Excess pyruvate since it is anaerobic will will be used in other reaction
form lactate. - After binding with ACP complex it will
- Lactate In muscle tissue promote cramps react with synthase having a thiol group
- To prevent cramps, lactate must travel resulting to a transfer.
back to liver - Acetyl synthase complex will now be
- High NAD to NADH outside liver while in condensed with malonyl ACP
the liver lower NAD to NADH ratio Step 2: The condensation step:
Glucose - the Carbon 2 fragment on the synthase
- Catabolism is Glycolysis is now condensed with a Carbon 3
- Anabolism is Gluconeogenesis fragment in a reaction that gives off
Glycogen carbon dioxide .
- Catabolism is Glycogenolysis
- Anabolism is Glycogenesis

Fatty Acid Biosynthesis


- While degradation of fatty acids takes
place in mitochondria under beta- - Condensation reaction with Malonyl
oxidation, the majority of fatty acid ACP
synthesis takes place in the cytosol. - Cleaving to form a carbon dioxide as by
These two pathways have in common that they product producing a four atom complex
both involve acetyl CoA.
- Acetyl CoA is the end product of each Step 3: The resulting 4-carbon fragment then
spiral of b-oxidation. undergoes three consecutive reactions:
- Fatty acids are synthesized two carbon reduction, dehydration, and reduction to give a
atoms at a time fully saturated C4 fragment. These three
- The source of these two carbons is the reactions are shown on the next two screens. As
acetyl group of acetyl CoA. you study them, note that they are the reverse
- Break down fatty acid uses two carbons of three steps in the b-oxidation of fatty acids.
- The key to fatty acid synthesis is the first - Ketone undergo reduction forming
step reaction via the multienzyme secondary alcohol
complex called acyl carrier protein, ACP- - Secondary alcohol undergo dehydration
SH. causing the double bond formation
- SH or thiol group binds to fatty acids - Reduction reaction where the double
- ACP has a side chain that carries the bond becomes a single bond
- growing fatty acid
- ACP rotates counterclockwise, and its Step 4: First reduction
side chain sweeps over the multienzyme
system (empty spheres)
Step 1: Acyl carrier protein (HS-ACP) picks up an
acetyl group from acetyl-CoA
Step 5: Dehydration Membrane Lipids
The two building blocks for the synthesis of
membrane lipids are:
a. Activated fatty acids in the form of their
acyl CoA derivatives.
- Double bond formation b. Glycerol 1-phosphate, which is obtained
Step 6: Second reduction by reduction of dihydroxyacetone
phosphate (from glycolysis):

- Step 5 of glycolysis where break down of


fructose 1 6 bisphosphate
- NADPH to produce NADP to form a - Glycerol 1-phosphate backbone of the
single bond membrane lipid
- Butyryl ACP complex will come back and c. Glycerol 1-phosphate combines with
start again in step number 2 two acyl CoA molecules, which may be
- Will extend until you get a longer fatty the same or different
acid chain

- Esterification in carbon 1 and 2


- Phosphatidate will become
sphingolipids
d. To complete the synthesis of a
phospholipid, an activated serine,
choline, or ethanolamine is added to the
phosphatidate by formation of a
- Higher fatty acids, for example C18 phosphoric ester.
(stearic acid), are obtained by addition of e. Sphingolipids and glycolipids are
one or more additional C2 fragments by assembled in similar fashion from the
a different enzyme system. appropriate building blocks.
- Unsaturated fatty acids are synthesized
from saturated fatty acids by enzyme- Cholesterol
catalyzed oxidation at the appropriate All carbon atoms of cholesterol and of all
point on the hydrocarbon chain. steroids synthesized from it are derived from the
- The structure of NADP+ is the same as two-carbon acetyl group of acetyl CoA.
NAD+ except that there is an additional - Synthesis starts with reaction of three
phosphate group on carbon 3’ of one of molecules of acetyl CoA to form the six-
the ribose units. 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.
- Amine functional group transfers to c
double bond o

- 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, cholesterol and bile acids.

- Isopentenyl pyrophosphate (C5 ) is the


building block for the synthesis of
geranyl pyrophosphate (C10) and
farnesyl pyrophosphate (C15).
- Some will come from pyruvate,
phosphoenol pyruvate, oxaloacetate,
malate and aspartate.
- Geranyl and farnesyl pyrophosphate are
the starting material for bile acids and
steroids.

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 alpha
ketoglutarate, a citric acid cycle
intermediate:

Glutamate in turn serves as an intermediate in


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

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