1. Metabolism of amino acids, purine and pyrimidine bases
Pavla Balínová

2. Amino acids (AAs) Sources of AAs: diet synthesis de novo
protein degradation
dietary proteins proteosynthesis
body proteins AAs pool N-compound synthes.
de novo biosynthesis degradation (E,glc,fat)

3. Biosynthesis of amino acids (AA)
Humans can synthesize only 10 of the 20 AA.
Essential AA = AA that cannot be synthesized „de novo“. They must be obtained from diet.
Nonessential AA:
Ala is synthesized from pyruvate.
Cys is synthesized from Met and Ser.
Tyr is formed by hydroxylation from Phe.
Tyr
Val
Ser
Trp
Pro
Thr
Gly
Phe
Glu
Met
Gln
Lys
Cys
Leu
Asp
Ile
Asn
His
Ala
Arg
Nonessential AA
Essential AA

4. Synthesis of AAs in a human body - 5 substrates -
oxaloacetate → Asp, Asn
-ketoglutarate → Glu, Gln, Pro, (Arg)
pyruvate → Ala
3-phosphoglycerate → Ser, Cys, Gly
Phe → Tyr

5. Synthesis of thyrosine from phenylalanine
Figure is found at

6. Formation of activated methionine = S-adenosylmethionine (SAM)
SAM is used as –CH3 group donor in metabolic methylations
Figure is found at

7. Synthesis of Cys from Met and Ser
Figure is found at

8. Degradation of AA
20 different multienzyme sequences exist for catabolism of AAs. All common 20 AAs are converted to only
7 compounds:
pyruvate
acetyl-CoA
acetoacetyl-CoA
α-ketoglutarate
succinyl-CoA
fumarate
oxaloacetate

9. Three types of reactions are typical for degradation of AAs:
Transamination
2. Deamination
3. Decarboxylation

10. Transamination = an exchange of –NH2 between amino acid and α-ketoacid
These reactions are catalyzed by transaminases (aminotransferases). Most of them require α-ketoglutarate as an acceptor of –NH2.
Coenzyme of transaminases: pyridoxal phosphate (vit. B6 derivative)
Figure is found at

11. Aminotransferases (transaminases) important in medicine
Alanine aminotransferase
(ALT)
Aspartate aminotransferase
(AST)
Figure was adopted from Devlin, T. M. (editor): Textbook of Biochemistry with Clinical Correlations,
4th ed. Wiley‑Liss, Inc., New York, ISBN 0‑471‑15451‑2

12. Deamination e. g. oxidative deamination of Glu
Glu → α-ketoglutarate by glutamate dehydrogenase
Figure is found at

13. Decarboxylation → primary amines a) decarboxylation of His → histamine
b) decarboxylation of Trp → serotonin
c) decarboxylation of Tyr → epinephrine and norepinephrine
d) decarboxylation of Glu → GABA (γ-aminobutyrate)
Figure is found at

14. Ammonia transport and detoxification
Glutamine (Gln) is the major transport form of ammonia.
Figure is found at

15. Glucose-Alanine cycle
Figure is found at

16. Urea cycle (ornithine cycle)
substrates: NH4+, HCO3-, Asp, ATP
product: urea
function: synthesis of non-toxic urea
subcellular location: mitochondria and cytosol
organ location: liver
regulatory enzyme: carbamoyl phosphate synthetase I

17. Urea cycle (ornithine cycle)
Figure is found at

18. The fate of carbon skeletons of AA during catabolism
The strategy of the cell is to convert carbon skeletons to compounds useful in gluconeogenesis or CAC.
Glucogenic AAs = AA that can form any of intermediates of carbohydrate metabolism
Gly, Ala, Ser, Cys, Thr → pyruvate
Glu, Pro, Arg, His → Glu → α-ketoglutarate
Met, Ile, Val → succinyl-CoA
Ketogenic AAs are converted to acetyl-CoA and acetoacetyl-CoA. They yield ketone bodies.
Leu, Lys
● Glucogenic-ketogenic AAs = Thr, Phe, Tyr, Ile

19. Figure is found at http://www. biocarta

20. De novo synthesis of purine nucleotides
Figure is found at

21. Important notes about biosynthesis of purine nucleotides
Subcellular location: cytoplasm
PRPP = phosphoribosyl pyrophosphate is derived from ribose-5-P
IMP = inosine monophosphate serves as the common precursor of AMP and GMP synthesis
Gln, Gly, Asp are donors of C and N atoms
CO2 is a source of C
C1 units are transferred via tetrahydrofolate
„Salvage pathway“:
purines from normal turnover of cellular NA can be converted to nucleoside triphosphates
substrates: purine bases, PRPP, ATP

22. Degradation of purine nucleotides
→ uric acid is formed by enzyme xanthine oxidase

23. De novo synthesis of pyrimidine nucleotides
Figure is found at

24. Important notes about synthesis of pyrimidine nucleotides
Carbamoyl phosphate is formed from Gln and CO2
(2 ATP are consumed). This reaction is catalyzed by carbamoyl-P synthetase II (cytosolic enzyme) = regulatory step
pathway occurs in cytoplasm but formation of orotate occurs in mitochondrion → orotate is linked by PRPP → OMP → UMP
UMP → UTP → CTP
TTP
● UTP inhibits regulatory enzyme, activator is PRPP
„Salvage pathway“:
● pyrimidine nucleosides are phosphorylated (ATP) to nucleotides
TTP

25. Degradation of pyrimidine bases
→ β-amino acids are formed