/
Aromatic amino acid metabolism Aromatic amino acid metabolism

Aromatic amino acid metabolism - PowerPoint Presentation

phoebe-click
phoebe-click . @phoebe-click
Follow
517 views
Uploaded On 2017-05-29

Aromatic amino acid metabolism - PPT Presentation

Aromatic amino acid contains aromatic ring They are PhenylalanineBenzene ring or phenyl Tyrosinephenol Tryptophanindole Phenylalanine and Tryptophan are essential amino acids ID: 553560

phenylalanine tyrosine tryptophan amino tyrosine phenylalanine amino tryptophan aromatic phosphate acids form anthranilate chorismate synthase shikimate amp precursor prephenate

Share:

Link:

Embed:

Download Presentation from below link

Download Presentation The PPT/PDF document "Aromatic amino acid metabolism" is the property of its rightful owner. Permission is granted to download and print the materials on this web site for personal, non-commercial use only, and to display it on your personal computer provided you do not modify the materials and that you retain all copyright notices contained in the materials. By downloading content from our website, you accept the terms of this agreement.


Presentation Transcript

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 tyrosineSlide13
Slide14

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 dopamineSlide17
Slide18

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.Slide21
Slide22

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 arthritisSlide23
Slide24

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

Thank you