1. AMINO ACID METABOLISMS

2. Amino acid structure

4. Non essential amino acids
Essential amimo acids
Val, Leu Ile Phe Met, Thr, Lys, Arg*, Hys*, Trp
Non essential amino acids
Gly, Ala, Ser, Pro, Hyp1, Cys, Tyr, Asn, Gln, Asp, Glu, Hyl1

5. AMINO ACID METABOLISM NONPROTEIN DERIVATIVES BODY PROTEINS
Proteosynthesis
Degradation
NONPROTEIN
DERIVATIVES
Porphyrins
Purines
Pyrimidines
Neurotransmitters
Hormones
Komplex lipids
Aminosugars
Digestion
AMINO ACIDS
DIETARY
PROTEINS
GLYCOLYSIS
KREBS CYCLE
(Carbon skeleton)
Conversion
Transamination
UREA
NH3
GLUCOSE CO2 KETONBODIES

6. Enzymes cleaving the peptide bonds
Endopeptidases – hydrolyse the peptide bond inside a chain
Pepsin, trypsin, chymotrypsin
Exopeptidases – split the peptide bond at the end of a protein molecule
Aminopeptidase, carboxypeptidases
Dipeptidases
Pepsin (pH 1.5 – 2.5) – peptide bond derived fromTyr, Phe,
bonds between Leu and Glu
Trypsin (pH 7.5 – 8.5) – bonds between Lys a Arg
Chymotrypsin (pH 7.5 – 8.5) – bonds between Phe a Tyr

7. General reactions of amino acids
deamination
a-keto acid
NH2 transamination a-keto acid
+ amino acid
R C H
COOH decarboxylation amine
General reactions of amino acids are transamination and
deamination of a-amino group
Decarboxylation reaction gives biologically active amines

8. Transamination reactions
The glutamate which is produced by these transaminase reactions is oxidatively deaminated by glutamate dehydrogenase to release ammonium:

9. Transamination reactions
(enzymes aminotransferases)
Transaminases are enzymes which transfer the amino group from an amino acid to a keto acid,
usually alpha-ketoglutarate, essentially swapping an amino group with a keto group:
(Alanine-a-ketoglutarate transferase)
another similar reaction yields more common products:
(aspartate-a-ketoglutarate transferase)

10. These reactions are mediated by pyridoxal phosphate (PLP),
a derivative of pyridoxine (vitamin B6):

11. pyridoxal phosphate pyridoxamine phosphate
pyridoxamine phosphate pyridoxal phosphate

12. Clinicaly important transaminases
ALT
Alanine-a-ketoglutarate transferase
Clinical marker for irreversibile liver damage
AST
aspartate-a-ketoglutarate transferase
Clinical marker for irreversibile myocardial damage

13. Amino acids with three carbons are converted to pyruvate: Alanine
Serine
Cysteine
Serine is deaminated by serine dehydratase to form pyruvate + NH4+ in a reaction which doesn't involve the transaminase but does use pyridoxal phosphate (PLP) as a reactive group.
Similarly, threonine can be dehydrated and deaminated to yield pyruvate.
Glycine can be converted to serine for degradation, or it can be cleaved to release CO2, NH4+ and an activated one-carbon unit. In addition, three carbons from tryptophan are converted to pyruvate by way of alanine.

14. Amino acids with three carbons are converted to pyruvate

15. Amino acids with five carbons are converted to alpha-ketoglutarate:
Arginine
Glutamine
Histidine
Proline
These amino acids are first converted to glutamate which is transaminated to alpha-ketoglutarate.

17. Some amino acids are converted to succinyl-CoA: Methionine Valine
Isoleucine
These amino acids are converted to propionyl-CoA
which is carboxylated to methylmalonyl-CoA
which is converted to succinyl-CoA.
This last step is an isomerization catalyzed by Methylmalonyl-CoA mutase, an enzyme which uses cobalamin (vitamin B12).

18. Leucine and Lysine are converted to acetyl-CoA and acetoacetate:
Degradation of valine, leucine, and isoleucine requires the oxidative decarboxylation of an alpha-keto acid.
If this enzyme is defective, these acids accumulate in the blood and urine, resulting in maple syrup urine disease (branched chain ketoaciduria).
This disease is characterized by physical and mental retardation.

19. Phenylalanine and Tyrosine are converted to fumarate and acetoacetate
A serious disease results from the inability to oxidize phenylalanine by a defective phenylalanine hydroxylase.
This results in high levels of phenylpyruvate developing (phenylpyruvate is the result of transamination of phenylalanine with an amino acid).
The disease is phenylketonuria (PKU), and results in severe mental retardation and shortens the life span so that half the carriers are dead at 20 and 75% are dead at 30 if it is untreated. It is a genetic disorder and can result from aberrant splicing of the normal phenylalanine hydroxylase transcript.
Therapy for the disease involves restricting the intake of phenylalanine, and must be started immediately after birth. Screening for the disease occurs at birth so that as many effects as possible can be avoided.

20. Degradation of aminoacids for saccharides and lipides synthesis
The twenty common amino acids are degrade to a total of seven different compounds, all of which are related to the citric acid cycle:
Degradation of aminoacids
gives intermediates
for saccharides and lipides synthesis

21. Interconversion of amino acids and intermediates
of carbohydrate metabolism

22. Glucogenic ketogenic glucogenic + ketogenic
Amino acids
Glucogenic ketogenic glucogenic +
ketogenic
Ala Hyp Leu Ile
Arg Met Lys
Asp Pro Phe
Cys Ser Trp
Glu Thr Tyr
Glu Val
Gly
His

23. Enzymes which metabolised amino acides containe vitamines as cofactors
Vater soluble vitamins B
THIAMINE B1 (thiamine diphosphate)
oxidative decarboxylation of a-ketoacids
RIBOFLAVIN B2 (flavin mononucleotide FMN, flavin adenine dinucleotide FAD)
oxidses of a-aminoacids
NIACIN B3 – nicotinic acid (nikotinamide adenine dinucleotide NAD+
nikotinamide adenine dinukleotide phosphate NADP+)
dehydrogenases, reductase
PYRIDOXIN B6 (pyridoxalphosphate)
transamination reaction and decarboxylation
FOLIC ACID (tetrahydropholate)
Meny enzymes of amino acid metabolism

24. Nitrogenous derivatives of amino acids
Glycine
heme, purine, creatine, conjugation of bile acids
Histidine
histamine
Ornithine a arginin
creatine, polyamines (spermidine, spermine)
Tryptophan
serotonine (melatonine)
Tyrosine
Epinephrine, norepinephrine
Glutamic acid
g-aminobutyric acid (GABA)

25. Aspartame (NutraSweet) consists of a methly ester of L-aspartate and L-phenylalanine: