1. Amino Acid Biosynthesis & Degradation
Learning Objectives :
1. Know the groups of a.a. biosynthetic families
2. The enzymes and coenzymes involved in the synthetic pathways
3. The enzyme deficiencies of each pathway.
4. The consequences of the inborn errors of metabolism

2. Amino Acid Biosynthetic Families, Grouped by Metabolic Precursor
α-Ketoglutarate Pyruvate
Glutamate Alanine
Glutamine Valine*
Proline Leucine*
Arginine Isoleucine*
3-Phosphoglycerate Phosphoenolpyruvate and
Serine erythrose 4-phosphate
Glycine Tryptophan*
Cysteine Phenylalanine*
Oxaloacetate Tyrosine
Aspartate Ribose 5-phosphate
Aspargine Histidine*
Methionine*
Threonine*
Lysine*

3. Biosynthetic Families of Amino Acids in Bacteria and Plants

4. Pyruvate as an Entry Point into Metabolism
Pyruvate is the entry point of the three-carbon amino acids alanine, serine, and cysteine into the metabolic mainstream
The transamination of alanine directly yields pyruvate.
Glutamate is then oxidatively deaminated, yielding NH4+ and regenerating
α-ketoglutarate. The sum of these reactions is

5. Another simple reaction in the degradation of amino acids is the deamination of serine to pyruvate by serine dehydratase

6. Methionine Metabolism

7. Activated Methyl Cycle
Activated Methyl Cycle. The methyl group of methionine is activated by the formation of Sadenosylmethionine

8. Oxygenases Are Required for the Degradation of Aromatic Amino Acids
The degradation of phenylalanine begins with its hydroxylation to tyrosine, a reaction catalyzed by phenylalanine hydroxylase. This enzyme is called a monooxygenase (or mixed-function oxygenase) because one atom of O2 appears in the product and the other in H2O.

9. Phenylalanine & Tyrosine Degradation

10. Phenylalanine Catabolism Is Genetically Defective in Some People
Genetic defects of amino acid metabolism can cause defective neural development and mental retardation. In most such diseases specific intermediates accumulate. For example, a genetic defect in phenylalanine hydroxylase, The first enzyme in the catabolic pathway for phenylalanine , is responsible for the disease phenylketonuria (PKU), the most common cause of elevated levels of phenylalanine (hyperphenylalaninemia).

11. The incidence of phenylketonuria is about 1 in 20,000 newborns
The incidence of phenylketonuria is about 1 in 20,000 newborns. The disease is inherited in an autosomal recessive manner. Heterozygotes, who make up about 1.5% of a typical population, appear normal. Carriers of the phenylketonuria gene have a reduced level of phenylalanine hydroxylase, as indicated by an increased level of phenylalanine in the blood

12. Because the major outflow pathway is blocked in phenylketonuria, the blood level of phenylalanine is typically at least 20-fold as high as in normal people. Minor fates of phenylalanine in normal people, such as the formation of phenylpyruvate, become major fates in phenylketonurics.

14. Alcaptonuria is an inherited metabolic disorder caused by the absence of homogentisate oxidase.

16. The Branched-Chain Amino Acids Yield Acetyl CoA, Acetoacetate, or Propionyl CoA
The degradative pathways of valine and isoleucine resemble that of leucine. After transamination and oxidative decarboxylation to yield a CoA derivative, the subsequent reactions are like those of fatty acid oxidation.
Isoleucine yields acetyl CoA and propionyl CoA, whereas valine yields CO2 and propionyl CoA.

18. Tryptophan Degradation
Tryptophan Degradation. The pathway for the conversion of tryptophan into alanine and acetoacetate

19. Histidine Degradation Conversion of histidine into glutamate
Glutamate Formation. Conversion of proline and arginine into glutamate

20. Succinyl CoA Formation
Succinyl CoA Formation. Conversion of methionine, isoleucine, and valine into succinyl CoA

21. Some Human Genetic Disorders Affecting Amino Acid Catabolism
Medical condition
Defective process
Defective enzyme
Symptoms and effects
Albinism
Melanin synthesis
from tyrosine
Tyrosine 3-monooxygenase
(Tyrosinase)
Lack of pigmentation:
white hair, pink skin
Alkaptonuria
Tyrosine degradation
Homogentisate
1,2-dioxygenase
Dark colour of urine; late developing
Arthritis
Argininemia
Urea synthesis
Arginase
Mental retardation

22. Medical condition
Defective process
Defective enzyme
Symptoms and effects
Carbamoyl phosphate synthetase I
deficiency
Urea synthesis
Carbamoyl phosphatase I
Lethargy; convulsions;
early death
Homocystinuria
Methionine degradation
Cystathionine –β synthase
Faulty bone development;
mental
retardation
Maple syrup urine disease (branched-
chain ketoaciduria)
Isoleucine, leucine,
& Valine degradation
Branched-chain –α keto acid dehydrogenase
complex
Vomiting; convulsions mental retardation, early death

23. Medical condition Defective process Defective enzyme
Symptoms and effects
Methylmalonic
acidemia
Conversion of propionyl-CoA to succinyl-CoA
Methylmalonyl-CoA
mutase
Vomiting; convulsions;
mental retardation;
Early death
Phenylketonuria
Conversion of phenylalanine to tyrosine
Phenylalanine hydroxylase
Neonatal vomiting
Mental retardation

24. Inherited defects of a. a. met
Inherited defects of a.a. met. almost result in mental retardation or other developmental abnormalities as a result of harmful accumulation of metabolites .

25. END of PROTEIN METABOLISM