INTERNATIONAL UNIVERSITY

SCHOOL OF BIOTECHNOLOGY

Amino Acid
CHAPTER 6:
Degradation and
Synthesis

BIOCHEMISTRY
June 14, 2024 1
 LEARNING OBJECTIVES

1. To understand the way to go of each

amino acid
2. To know the way to synthesize the
nonessential amino acids
3. To know some human diseases
associated with amino acid metabolism

June 14, 2024 2

 Contents
• Amino acids that form oxaloacetate
• Amino acids that form -ketoglutamate
• Amino acids that form pyruvate
• Amino acids that form fumarate
• Amino acids that form succinyl CoA
• Degradation and Resynthesis of
Methionine
• Amino acids that form acetyl CoA or
acetoacetyl CoA
June 14, 2024 3
 Contents
•Folic Acid in Amino Acid Metabolism
•Tetrahydrofolate Derivatives
•Two Reactions using Vitamin B12
•Biosynthesis of Nonessential Amino
Acids
Diseases Associated with Amino Acid
Metabolism
Maple Syrup Urine Disease (MSUD)
Homocystinuria
Phenylketonuria (PKU)
June 14, 2024 4
Glucogenic and Ketogenic Amino Acids

Amino Acids whose catabolism

yields pyruvate or one of the
intermediates of the TCA cycle

Amino Acids whose catabolism

yields either acetoacetate or
June 14, 2024
acetyl CoA or acetoacetyl CoA5
 Amino Acid Catabolism
• Amino acids that form oxaloacetate

June 14, 2024 6

 Amino Acid Catabolism
• Amino acids that form oxaloacetate

Acute lymphoblastic leukemia (ALL)

June 14, 2024 7

 Amino Acid Catabolism
• Amino acids that form oxaloacetate
• Amino acids that form -ketoglutarate
glutaminase transamination
a. Glutamine Glutamate -ketoglutarate
deamination
oxidation
b. Proline

c. Arginine Ornithine

d. Histidine

FIGLU test: a urine test, an indicator of

Vitamin B12 or folic acid deficiency or liver
disease
June 14, 2024 8
 Amino Acid Catabolism
• Amino acids that form oxaloacetate
• Amino acids that form -ketoglutarate
• Amino acids that form pyruvate
-KG Glutamate

a. Alanine
ALT

N5,N10-methylene-THF THF
Serine
b. Glycine Serine Serine dehydrogenase
Hydromethyl-
transferase
CO2+NH3

reduction
c. Cystine Cysteine

d. Threonine
June 14, 2024 9
-ketobutyrate Succinyl CoA
 Amino Acid Catabolism
• Amino acids that form oxaloacetate
• Amino acids that form -ketoglutarate
• Amino acids that form pyruvate
• Amino acids that form fumarate

June 14, 2024 10

 Amino Acid Catabolism
• Amino acids that form oxaloacetate
• Amino acids that form -ketoglutarate
• Amino acids that form pyruvate
• Amino acids that form fumarate
• Amino acids that form succinyl CoA

a. Valine, isoleucine: branched-chain amino acids.

June 14, 2024 11

 Branched-chain Amino Acids Catabolism
Leucine
Valine
Isoleucine
Branch-chain -amino
1. Transamination acid aminotransferase
Maple syrup urine
disease Branch-chain -keto
2. Oxidative Decarboxylation acid dehydrogenase
(coenzymes: TPP, CoA,
lipoic acid,
NAD and FAD)
3. Dehydrogenation

Acetyl CoA
Propionyl CoA
Acetoacetate
+
Acetyl CoA
June 14, 2024 Succinyl CoA 12
 Amino Acid Catabolism
• Amino acids that form oxaloacetate
• Amino acids that form -ketoglutamate
• Amino acids that form pyruvate
• Amino acids that form fumarate
• Amino acids that form succinyl CoA

a. Valine, isoleucine: branched-chain amino acids.

b. Threonine:

Threonine -ketobutyrate
pyruvate
propionyl

June 14, 2024 Succinyl CoA 13

 Amino Acid Catabolism
• Amino acids that form oxaloacetate
• Amino acids that form -ketoglutamate
• Amino acids that form pyruvate
• Amino acids that form fumarate
• Amino acids that form succinyl CoA

a. Valine, isoleucine: branched-chain amino acids.

b. Threonine
c. Methionine

June 14, 2024 14

 Degradation and Resynthesis of Methionine
L-Methionine
S-Adenosyl ATP
methionine
synthase Pi+PPi
CH3 the major methyl-group donor
- - - - -

Adenosine- S+ 2P
in one carbon metabolism
CH2
CH2 S-Adenosylmethionine (SAM)
HCNH3+
COO- Methyl acceptors
Methyltransferases

Methylated products
Adenosine- S
- - - -

CH2
CH2 S-Adenosylhomocysteine
HCNH3 +

COO-

Adenosine
Vascular diseases
SH
- - - -

CH2
CH2 L-homocysteine
June 14,HCNH
+
2024 -3 15
COO
 Degradation and Resynthesis of Methionine
L-Methionine
1) Resynthesis of methionine
S-Adenosylmethionine (SAM) 2) synthesis of cysteine
S-Adenosylhomocysteine Methylcobalamin
(Methyl-B12)
L-Methionine
L-homocysteine Homocystein
L-Serine methyltransferase
Cystathionine
synthase
B6 N5-Methyltetrahydrofolate Tetrahydrofolate
H2O
Cystathionine
H2O
Cystathionase B6

-ketobutyrate+NH 4
+

L-cysteine
Propionyl CoA Succinyl CoA

Low concentrations of folate, vitamin B12 or B6 may increase the level of homocysteine.
Elevated
June 14,homocysteine
2024 level is an independent risk factor for heart disease and stroke.
16
 Amino Acid Catabolism
• Amino acids that form oxaloacetate
• Amino acids that form -ketoglutamate
• Amino acids that form pyruvate
• Amino acids that form fumarate
• Amino acids that form succinyl CoA
• Amino acids that form acetyl CoA or acetoacetyl
CoA
a. Leucine, isoleucine: branched-chain amino acids.
b. Lysine:
c. Tryptophan
acetoacetyl CoA

Alanine + acetoacetyl CoA

June 14, 2024 17

 Folic Acid in Amino Acid Metabolism

Folic acid
(folate)
Pterin
p-aminobenzoate dihydrofolate
reductase
Glutamate
(DHFR)

Dihydrofolate
(DHF)

dihydrofolate
a) THFs are reduced forms of folic acid reductase
b) addition of glutamate residues bound (DHFR)
to one another

Tetrahydrofolate
June 14, 2024
(THF) 18
 Tetrahydrofolate Derivatives
THF
+ Purine
Formate
N10-Formyl-THF
H2O

THF
+
Histidine NADPH+H+

N5, N10 -Methenyl-THF

NADP+
THF
+
Glycine Thymine
Serine
Formaldehyde NADH+H+

N5, N10 -Methylene-THF

NAD+

Purpose: carry and transfer the oxidation

state of one carbon unit (methane,
methanol, formadehyde and Methionine
formic acid )
June 14, 2024 19
N5-Methyl-THF
 Two Reactions using Vitamin B12
1. Resynthesis of methionine from homocysteine
Methylcobalamin
(Methyl-B12)
L-Methionine
L-homocysteine Homocystein
methyltransferase

N5-Methyltetrahydrofolate Tetrahydrofolate

2. Synthesis of succinyl CoA:

June 14, 2024 20

Biosynthesis of Nonessential Amino Acids

A. Synthesis from -keto acids

June 14, 2024 21

Biosynthesis of Nonessential Amino Acids

A. Synthesis from -keto acids

B. Synthesis by amidation

a. Glutamine

b. Asparagine Glutamine + ATP Glutamate + ADP

Aspartate Asparagine
Asparagine
June 14, 2024 synthetase 22
Biosynthesis of Nonessential Amino Acids

A. Synthesis from -keto acids

B. Synthesis by amidation

C. Proline: from glutamate by cyclization and reduction reactions

D. Serine, glycine and cysteine

Serine
Homocysteine
3-P-Glycerate

Glycinee Cystathionine
-ketoglutarate

Serine Cysteine

Pyruvate
June 14, 2024 23
Biosynthesis of Nonessential Amino Acids

A. Synthesis from -keto acids

B. Synthesis by amidation

C. Proline

D. Serine, glycine and cysteine

Serine
Homocysteine
3-P-Glycerate

Glycinee Cystathionine
-ketoglutarate

Serine Cysteine

Pyruvate
June 14, 2024 24
Biosynthesis of Nonessential Amino Acids

A. Synthesis from -keto acids

B. Synthesis by amidation

C. Proline

D. Serine, glycine and cysteine

E. Tyrosine

June 14, 2024 25

Diseases Associated with Amino Acid Metabolism

A. Maple Syrup Urine Disease (MSUD)

Partial or complete deficiency in branched-chain

-ketoacid dehydrogenase

-ketoacid dehydrogenase

Neurological problems, mental retardation

Physical disabilities and death

Treatment: limited leucine, isoleucine and valine

June 14, 2024 26

Diseases Associated with Amino Acid Metabolism

A. Maple Syrup Urine Disease (MSUD)

B. Homocystinuria
Defect in cystathionine -synthase Methionine

Ectopic lentis, skeletal abnormalities,

Premature arterial disease, osteoporosis
and mental retardation.

Treatment: restriction of methionine intake,

administration of Vitamins 6,
B12 and folate.

June 14, 2024 27

Diseases Associated with Amino Acid Metabolism

A. Maple Syrup Urine Disease (MSUD)

B. Homocystinuria

C. Phenylketonuria (PKU)

June 14, 2024 28

 Phenylketonuria (PKU)
•Hyperphenylalaninemia
•Defect in the conversion of Phenylalanine to Tyrosine
•Deficiency in any of the following enzymes:
1) phenylalanine hydroxylase (majority) 2) BH2 synthetase 3) BH2 reductase

(BH4)
NADP+
Dihydrobiopterin
reductase

(BH2) NADPH + H+
Dihydrobiopterin
synthetase

June 14, 2024 GTP 29

 Symtoms associated with PKU
•Elevated phenylalanine and low level of Tyrosine

•CNS Symptoms:
Mental retardation, failure to walk or talk, seizure,
and failure to grow

•Hypopigmentation:fair hair, light skin

color and blue eyes, no melanin

June 14, 2024 30

 Phenylketonuria (PKU)

(BH4)
NADP+
Dihydrobiopterin
reductase

(BH2) NADPH + H+
Dihydrobiopterin
synthetase

GTP

Treatment: 1: deficiency in phenylalanie hydroxylase (PAH):

special diet low in phenylalanine for the rest of their life,
injectable PAH
June 14, 2024 2: deficit in BH4: administration of BH4 31
Biosynthetic reactions involving tetrahydrobiopterin

June 14, 2024 32

 Thank you for your kindly listening

June 14, 2024 33