Amino acid catabolism

- During times of starvation, amino acids are used to replenish

TCA cycle intermediates and as precursors for gluconeogenesis
- Organisms with a diet rich in proteins can oxidize excess
amino acids as fuels
- Amino acids are not stored

- In animals, amino acids (in the form of polypeptides) are the

major source of nitrogen.
- What is the key difference between amino acids and the
other 2 types of oxidizable molecules?

Transamination (in liver):

Universal
amino group
acceptor

PLP : pyridoxal phosphate

Deamination (oxidative deamination) - in liver:

Dehydrogenation (oxidation)

Glutamate
Dehydrogenase

deamination
urea

Transamination + Deamination = Transdeamination

How do non-hepatic tissues remove ammonia?

Amino group

Amide group

Transport of glutamine to liver:

Removal of excess ammonia from muscle

In liver cells:

The Urea Cycle

Formation of carbomoyl phosphate

Argininosuccinate synthase reaction:

Transamination

Arginase

Lyase

Links between the urea cycle and the TCA cycle

Cytosolic fumarase

transamination

OAA

fumarase

Kreb
Bicycle

Oxidation of the carbon skeletons in amino acids

Amino acids giving rise to -ketoglutarate:

Glutamate, Glutamine, Histidine
Methyl group
transfer

Histidine
ammonia
lyase

(oxidative
deamination)

Amino acids giving rise to -ketoglutarate:

Arginine and Proline

-Ketoglutarate

Amino acids giving rise to oxaloacetate:

Aspartate and Asparagine

(Asn)
asparaginase

(Asp)
aspartate
aminotransferase

Amino acids giving rise to pyruvate:

Cysteine, tryptophan, threonine, serine, glycine and alanine

pyruvate

-ketoglutarate

glutamate

H2O
5, 10-Methylene THF

THF

Amino acids giving rise to succinyl-CoA:

Methionine, threonine

Cystathionine
-Ketobutyrate
dehydrogenase

Propionyl-CoA + CO2
NADH

Succinyl-CoA

NAD+

Branched chain amino acid (BCAA) catabolism: Valine, Isoleucine, Leucine

Aromatic amino acid metabolism:

Phenylalanine and tyrosine
NADH
NAD+
+ H+
O2
H2 O
Phenylalanine
hydroxylase
X
Phenylketonuria
(1 in 10,000 newborns)

COOCH2

H2 O

COOO

Phenylacetate

CO2
COO-

CH2
HO

CH
CH2

Phenylpyruvate

Phenyllactate

Accumulates in
phenylketonuria patients

phenylketonurics:
contains phenylalanine

Aspartame
-Artificial sweetener
-Dipeptide of phenylalanine methyl ester and aspartate

Amino Acid Biosynthesis

The Nitrogen Cycle

[N2 as electron acceptor]

Bacteria (symbiotic in legume plants)

Denitrification

Nutrifying
bacteria

Plants, bacteria, fungi

Nitrogen fixation by the nitrogenase complex:

N2 + 8 H+ + 8 e- + 16 ATP 2NH3 + H2 + 16 ADP + 16 Pi

Nitrogen-fixing bacteria in root nodules

of legume plants

Ammonia Assimilation
- Entry point for ammonia: glutamate (Glu) and glutamine (Gln)

- Plants and bacteria: an additional pathway

NAD(P)H + H+

NAD(P)+

Glutamate
synthase

Essential and Non-essential Amino Acids (in mammals)

Essential Amino Acids:
Histidine, Isoleucine, Leucine, Lysine, Methionine
Phenyalanine, Tryptophan, Threonine, Valine

Non-essential amino acids (precursor):

Glutamate, glutamine, proline, arginine (-ketoglutarate)
Alanine (pyruvate)
Aspartate, asparagine (OAA)
Serine, glycine (3-Phophoglycerate)
*Cysteine (Methionine)
*Tyrosine (Phenylalanine)
*Conditional essential

Biosynthesis of Amino Acids

TRANSAMINATIONS

Example:
Glu

-KG

Glu-ala
aminotransferase

Aspartate and Asparagine Biosynthesis

Purine and pyrimidine

biosynthesis

Asparagine synthetase
amide group

PPi

amide
group

Proline Biosynthesis
NH3+

O
C

CH2

CH2

CH

Glutamate kinase
COO-

NH3+

ATP

ADP

Glutamate

CH2

CH2

CH

COO-

O
P O O

Glutamate-5-P
NAD(P)H + H+

Glutamate 5-P
Dehydrogenase
NAD(P)+
Pi

H
N
H 2C
H2C

CH
CH2

Proline

COO-

NAD(P)+

NAD(P)H + H+

HC

1-Pyrroline-5carboxylate reductase

H2C

N
CH

COO-

CH2

1-Pyrroline-5carboxylate

NH3+

Spontaneous
cyclization
H

CH2

CH2

CH

COO-

Glutamate-5-semialdehyde

Arginine Biosynthesis
(related to urea cycle)

(Acetyl-CoA)

N-acetyl group

Glutamate

acetylglutamate synthase

N-Acetylglutamate

N-Acetylglutamate

kinase

N-Acetyl--glutamyl

phosphate

N-Acetylglutamate

dehydrogenase

N-Acetylornithine

argininosuccinase
Fumarate

Serine and Glycine Biosynthesis

Glutamate
-Ketoglutarate

Pi

H2O

Phosphoserine
phosphatase

Phosphoserine
transaminase

H2O

Tyrosine synthesis from phenylalanine

NH3+
CH2 CH

O2
(defective in phenylketonurics)
Phenyalanine
hydroxylase
Mixed function oxidase
(mechanism similar to
fatty acid desaturase)

COO-

Phenylalanine

NADH + H+
tetrahydrobiopterin

NAD+
H2O

NH3+
HO

CH2 CH

Tyrosine

COO-

Cysteine synthesis from methionine

[ Plants and bacteria: SO42-

assimilation

cysteine ]

(from diet)

(SAM)

Methionine
cylce

Cysteine synthesis

(SAH)

Cysteine Biosynthesis

(CBS)

(From
methionine
cycle)

Homocystinuria
- Genetic defect in CBS
- Homocysteine level in blood stream
- Risks of heart diseases