Amino Acid Metabolism

Role of Amino Acids

• Protein monomeric units

• Energy source
• Precursors of other
biological molecules
 Protein Monomeric Units

H2O
R1 R2 R1 O R2
+ – + – + –
H3 N C COO + H3 N C COO H3 N C C NH C COO
H H H H
 Energy Source

ADP + Pi ATP

Amino Acids Waste Products

 Precursors
(Nitrogen-containing Compounds)

• Heme
• Nucleotides
• Amines
• Nucleotide
Coenzymes
• Glutathione
 Precursors
(a-ketoacids)

Pyruvate
Glucose
Amino Acids Oxaloacetate Fatty Acids
Ketone Bodies
-Ketoglutarate
 Classification
(Mammals)

• Essential amino acids

• Non-essential amino
acids
 Amino Acid Deamination
(First Reaction in Amino Acid Breakdown)

O
R C COO–
Nitrogen-containing compounds
-keto acid
R
+
H 3N C COO– Glutamate
H Fumarate O
KG
OAA C
Aminotransferases Aspartate H2 N NH2
(Transaminases) aKG Urea
Cycle Urea
 Aminotransferases
(Transaminases)

Amino Acid + -Ketoglutarate -Keto Acid + Glutamate

Glutamate + Oxaloacetate -Ketoglutarate + Aspartate

 Oxidative Deamination

Glutamate + NAD(P)+ + H2 O -Ketoglutarate + NH 4+ + NAD(P)H + H+

Glutamate
Dehydrogenase
 Amino Acid Oxidase

Amino Acid + FAD + H2 O -Keto Acid + NH 3 + FADH2

FADH2 + O2 FAD + H2 O2
 Transamination
(Reactions)

Amino Acid + Enzyme -Keto Acid + Enzyme–NH 2

Enzyme–NH 2 + -Ketoglutarate Enzyme + Glutamate

 Summary

Amino Acid + -Ketoglutarate -Keto Acid + Glutamate

 Degradative Fates of Glutamate
Regeneration of -Ketoglutarate

Carbon and Energy CO2

-ketoacid Nitrogen-containing compounds

Amino Acid Glutamate NH4+

Fumarate O
-KG OAA C
Aspartate H2 N NH2
KG Urea
Cycle Urea
Glutamate-Aspartate Aminotransferase

Glutamate + Oxaloacetate -Ketoglutarate + Aspartate

 Glutamate Dehydrogenase
(Oxidative Deamination)

NAD(P) + NAD(P)H + H +
H2C COO –
H2C COO – H2O NH 4+
H2C COO –
CH 2 CH 2
CH 2
+ – –
H3N C COO H2N C COO
O C COO –
H

Glutamate -Iminoglutarate -Ketoglutarate

 Formation of Urea

Aspartate + HCO3 - + NH4+ Urea

Urea Cycle
 Degradative Fates of Glutamate
Regeneration of -Ketoglutarate

Carbon and Energy CO2

-ketoacid Nitrogen-containing compounds

Amino Acid Glutamate NH4+

Fumarate O
-KG OAA C
Aspartate H2 N NH2
KG Urea
Cycle Urea
Urea Cycle
 Urea Cycle
(Introduction)

Proteins
Fats
Carbohy drates
(Nutrients)

ADP

ATP
Catabolism Anabolism
NADP+
(Oxidation) (Biosy nthesis)
NADPH

Intermediates

Waste
(CO2/Urea/etc.)
 Nitrogen Waste Products

N
N
O
O
O N N
C
NH 3 H2N NH 2 H
Ammonia Urea Uric Acid
(Vertebrates) (Birds and Reptiles)

Require less water for excretion

 Classification of Organisms
(Nitrogen Excretion Patterns)

• Ammonotelic: ammonia excreting

• Ureotelic: urea excreting
• Uricotelic: uric acid excreting
 Overall Urea Cycle
(Liver)

3ATP 2ADP + 2P i + AMP + PP i

H2C COO – O
+ HC COO –
NH 3 + HCO 3– + H3N C COO –
C +
H2N NH 2 –OOC CH
H
Aspartate Urea Fumarate
 Glutamate Dehydrogenase
(Generation of NH3)

Glutamate + NAD(P) +
+ H2O -Ketoglutarate + NH 3 + NAD(P)H + H +
 Carbamyl Phosphate Synthetase
(CPS)
(Mitochondrion)

2ATP 2ADP + Pi
O
NH3 + HCO3 – H 2N C OP

Carbamyl Phosphate
Carbamyl Phosphate Synthetase
(CPS)

• CPSI (Mitochondria)
– Uses NH3
– Urea Cycle
• CPSII (Cytosol)
– Uses Glutamine
– Pyrimidine Biosynthesis
 Ornithine Transcarbamylase
(OTC)
(Mitochondrion)
O NH 2
C
NH 3+ NH
Pi
O (CH 2)3 (CH 2)3
H2N C OP + +H N C COO – +H N C COO –
3 3
H H
Carbamoyl P
Ornithine Citrulline

Non-standard amino acids

(not present in proteins)
 Glutamate Dehydrogenase

Glutamate + NAD +
+ H2O -Ketoglutarate + NH 3 + NADH + H +
 Regeneration of Aspartate
(Cytosol)

NAD+ NADH + H +
Fumarate Malate Oxaloacetate Aspartate
Fumarase Malate Glu-Asp
Dehydrogenase Aminotransferase
Oxidation of 2 NADH Yields 6 ATP
 Activator

H2C COO –
O CH 2
H3C C N C COO –
H H

N-Acetylglutamate
Products of Amino Acid Breakdown

• Glucogenic • Ketogenic
– Pyruvate – Acetyl-CoA
– -Ketoglutarate – Acetoacetate
– Succinyl-CoA
– Fumarate
– Oxaloacetate
 Degradation of
amino acids to
one of seven
common
metabolic
intermediates.
Page 995
Animals cannot carryout net synthesis
of precursors of gluconeogenesis from
acetyl-CoA or acetoacetate
 Conversion of Pyruvate and
Oxaloacetate to PEP
(Gluconeogenesis)

ATP ADP + P i
O COOH
H 3C C COOH + HCO 3– CH2
(CO 2) Pyruvate O C COOH
Pyruvate Carboxylase
Oxaloacetate

COOH GTP GDP + CO2 OP

CH2 H 2C C COO – Glucose
PEP "Gluconeogenesis"
O C COOH Carboxykinase
Phosphoenolpyruvate
Oxaloacetate (PEP)
Degradation to Pyruvate

Alanine, Cysteine, Glycine,

Serine and Threonine
 Degradation of amino acids
• Amino acid breakdown can yield:
– Acetyl-CoA
--KG
– Succinyl-CoA
– OAA
– fumarate
 -KG is generated from five
amino acids
• Proline
• Glutamate
• Glutamine
• Arginine
• Histidine
 Four amino acids are converted to
Succinyl-CoA
• Methionine
– Converted to homocysteine through methyl group transfer,
generates cysteine as converted to -ketobutyrate
• Isoleucine
– Transamination, oxidative decarboxylation to acetyl-CoA and
propionyl CoA
• Valine
– Transamination, decarboxylation to propionyl CoA
• Threonine
- -ketobutyrate generated and converted to propionyl CoA
 Propionyl-CoA is
a common intermediate
for amino acids 
succinyl-CoA
 Branched-chain -keto acid
dehydrogenase complex

• In certain body tissues, this enzyme catalyzes the

oxidative decarboxylation of valine, isoleucine,
and leucine yielding CO2, and acyl-CoA
derivatives.
• Shares ancestry with pyruvate dehydrogenase
complex, -KG dehydrogenase complex – another
example of gene duplication
Branched-chain …complex
Asparagine and aspartate are degraded to OAA
 Fate of metabolites derived from
amino acids

• In addition to feeding the citric acid cycle, amino

acids can result in ketone bodies, while others are
gluconeogenic
 Ketone bodies

• The six amino acids that are

degraded to acetoacetyl-CoA
and/or acetyl-CoA) can be
converted to acetoacetate and
b-hydroxybutyrate
 Glucogenic amino acids
• Amino acids that are degraded to pyruvate, -KG,
succinyl-CoA fumarate, and/or OAA can be converted to
glucose