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AMINO ACID METABOLISMS
Amino acid structure
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
AMINO ACID METABOLISM
BODY PROTEINS
Degradation
Proteosynthesis
NONPROTEIN
DERIVATIVES
DIETARY
PROTEINS
GLYCOLYSIS
KREBS CYCLE
UREA
GLUCOSE
Conversion
(Carbon skeleton)
AMINO ACIDS
CO2
NH3
Porphyrins
Purines
Pyrimidines
Neurotransmitters
Hormones
Komplex lipids
Aminosugars
KETONBODIES
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
General reactions of amino acids
deamination
NH2
R
C
a-keto acid
transamination
a-keto acid
+ amino acid
H
COOH
decarboxylation
amine
General reactions of amino acids are transamination and
deamination of a-amino group
Decarboxylation reaction gives biologically active amines
Transamination reactions
The glutamate which is produced by these transaminase reactions is oxidatively
deaminated by glutamate dehydrogenase to release ammonium:
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)
These reactions are mediated by pyridoxal phosphate (PLP),
a derivative of pyridoxine (vitamin B6):
pyridoxal phosphate
pyridoxamine phosphate
pyridoxamine phosphate
pyridoxal phosphate
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
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.
Amino acids with three carbons are converted to pyruvate
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 alphaketoglutarate.
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).
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.
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.
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
Interconversion of amino acids and intermediates
of carbohydrate metabolism
Amino acids
Glucogenic
Ala
Arg
Asp
Cys
Glu
Glu
Gly
His
Hyp
Met
Pro
Ser
Thr
Val
ketogenic
Leu
glucogenic +
ketogenic
Ile
Lys
Phe
Trp
Tyr
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
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)
Aspartame (NutraSweet) consists of a methly ester
of L-aspartate and L-phenylalanine: