Aromatic amino acid contains aromatic ring They are PhenylalanineBenzene ring or phenyl Tyrosinephenol Tryptophanindole Phenylalanine and Tryptophan are essential amino acids ID: 553560
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Slide1
Aromatic amino acid metabolismSlide2
Aromatic amino acid contains aromatic
ring. They are:Phenylalanine(Benzene ring or phenyl).Tyrosine(phenol).Tryptophan(indole).Phenylalanine and Tryptophan are essential amino acids.Tyrosine can synthesis from Phenylalanine.Partially glucogenic and partially ketogenic.Only plants and microorganisms are able to synthesize aromatic amino acids.
AROMATIC AMINO ACIDSlide3
phenylalanine
tyrosine
tryptophanSlide4
Biosynthesis of aromatic amino acids starts with a common pathway, the
Shikimate pathway. The biosynthesis begins with Phosphoenolpyruvate and Erythrose-4- phosphate to form Shikimate. Shikimate then goes on to form the branch point intermediate Chorismate.Chorismate can be converted into
anthranilate
(L-Trp) or
prephenate (L-Phe and L-Tyr).Biosynthesis of aromatic amino acids: Slide5
Shikimate pathway
: 2-keto-3-deoxy-D-arabinoheptulosonate-7- phosphate synthase.: dehydroquinate
synthase.Slide6
: 3-dehydroquinate dehydrogenase, : shikimate dehydrogenase,: shikimate
kinase,
:
3-enolpyruvylshikimate-5-phosphate synthase, and : chorismate synthase.Slide7
Tryptophan
synthesisTryptophan is synthesized from chorismate in a 5-step process.Chorismate requires an amino group from the side chain of glutamine and releases pyruvate to form anthranilate.Anthranilate then undergoes condensation with
phosphoribosyl pyrophosphate (PRPP)
,
an activated form of ribose phosphate.The C-1 atom of ribose 5-phosphate becomes bonded to the nitrogen atom of anthranilate in a reaction that is driven by the hydrolysis of pyrophosphate.The ribose moiety of ribosylanthranilate undergoes rearrangement to yield enol-1-o-carboxylphenylamino-1- deoxyribulose-5-phosphate.This intermediate is dehydrated and then decarboxylated to indole-3- glycerol phosphate, which reacts with serine to form
tryptophan.Slide8
: anthranilate synthase, : anthranilate phosphoribosyl transferase, : N-(5’-phosphoribosyl)- anthranilate isomerase,Slide9
: indole-3-glycerol phosphate synthase, and : tryptophan synthase.Slide10
Tyrosine and phenylalanine
synthesisA mutase converts chorismate into prephenate, the immediate precursor of the aromatic ring of tyrosine and phenylalanine.Prephenate is oxidatively decarboxylated to p-
hydroxyphenylpyruvate.
Alternatively
, dehydration followed by decarboxylation yields phenyl pyruvate.These α-keto acids are then transaminated, with glutamate as amino group donor, to form
tyrosine and phenylalanine, respectively.Slide11
prephenate dehydratase
chorismate mutaseprephenate dehydrogenaseSlide12
Tyrosine can also be made by animals directly from phenylalanine
via hydroxylation at C-4 of the phenyl group by phenyl hydroxylase, which also participates in the degradation of phenylalanine.Hydroxylation of phenylalanine to form tyrosine involves the reductant tetrahydrobiopterin.Dihydrobiopterin is reduced to tetrahydrobiopterin by electron transfer from NADH.
Thus NADH is secondarily the e- donor for conversion of phenylalanine to tyrosineSlide13Slide14
Degradation of Aromatic Amino Acids
Transaminase.p-hydroxy-phenylpyruvate dioxygenase (vitamin C-dependent). homogentisate dioxygenase .
4-Maleylacetoacetate
isomerase
.fumarylacetoacetase.Slide15
Tryptophan
degradation requires several oxygenases
Pyruvate
Kynureninase
Formamidase
kynurenine hydroxylase
PLP
tryptophan pyrrolase
NADPH +
H+
NADP+
NAD and NADPSlide16
Amino Acids as Metabolic Precursors
Tyrosine is the precursor to several important molecules in metabolic signaling and neurotransmission, including epinephrine and dopamine. Tyrosine is oxidized by the enzyme tyrosine hydroxylase in a reaction requiring the enzyme cofactor tetrahydrobiopterin to form dihydroxyphenylalanine (L-DOPA), a metabolic precursor to dopamineSlide17Slide18
Tyrosine
is also the precursor to pigment molecules called melanins that are produced from dopaquinone. The two primary melanins are eumelanins, which are dark pigments having a brown or black color, and
pheomelanins
that have red or yellow color.
The yellow color of pheomelanin pigments comes from the sulfur in cysteine that is combined with dopaquinone. Slide19
T
hyroid hormones - Thyroxine (tetraiodothyronine) & triiodothyronine - are synthesized from the tyrosine residues of the protein thyroglobulin & activated iodine. Iodination of tyrosine ring occurs to produce mono & diiodotyrosine from which triiodothyronine (T3) & thyroxine (T4) are synthesized. The protein thyroglobulin undergoes proteolytic breakdown to release the free hormones - T3 & T4.Slide20
Tryptophan
, is the precursor to:Serotonin and melatonin.Niacin.Slide21Slide22
INBORN ERRORS OF AMINO ACIDS METABOLISM:
Alcaptonuria - inherited disorder of the tyrosine metabolism caused by the absence of homogentisate oxidase. homogentisic acid is accumulated and excreted in the urine turns a black color
upon exposure to air
In children:
urine in diaper may darken In adults: darkening of the ear dark spots on the on
the sclera and cornea arthritisSlide23Slide24
A genetic defect in the gene encoding phenylalanine hydroxylase is responsible for the metabolic disease
phenylketonuria (PKU). phenylketonuria (PKU)Diagnostic criteria: phenylalanine level in the blood FeCl3 test DNA probes (prenatal)
Defect in
myelination
of nervesThe brain weight is below normal.Mental and
physical retardations.The life expectancy is drastically shortened. Treatment: consists of limiting phenylalanine intake to levels barely adequate to support growth. Tyrosine, an essential nutrient for individuals with phenylketonuria, must be supplied in the diet. Slide25
The clinical symptoms of PKU are caused by the accumulation of
phenylalanine in the blood that is 30-50 times higher than normal. This high level of phenylalanine leads to the production of phenylalanine metabolites such as phenylpyruvate, phenylacetate
and
phenyllactate
, all of which are associated with the observed neurological and developmental problemsSlide26
NutraSweet contains a phenylalanine derivative
Phenylketonuriacs also have to be careful to avoid processed foods and beverages containing the food additive aspartame (aspartyl-phenylalanine methyl ester).Slide27
Albinism
– genetically determined lack or deficit of enzyme Tyrosinase
Tyrosinase
in
melanocytes oxidases tyrosine to DOPA and DOPA-chinone.Symptoms of albinism:
inhibition of production or lack of melanin in skin, hair, eyesincreased sensitivity to sunlightincreased risk of skin cancer development sun burnsphotophobiadecrease of vision acuitystrabismus, nystagmus
tyrosinase
Phenylalanine
Tyrosine
Tyroxine
Melanin
DOPA
Dopamine
Norepinephrine
EpinephrineSlide28
Tyrosinemia:
occur in several forms. They may be caused by a deficit of enzymes which catalyze either the transamination of tyrosine (II), or oxidation of p-hydroxyphenylpyruvate (III) and hydrolysis of fumarylacetoacetate (I). A low-tyrosine diet may be very useful.Plasma levels of tyrosine are elevated, and large amounts of tyrosine,
p
-hydroxyphenylpyruvate
, –lactate, and –acetate are excreted into the urine (tyrosyluria).Slide29
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