When Tyrosine becomes an essential amino acid

Answer to Question AM-06

 

Short answer: (g)

 

In patients with PKU, Tyrosine becomes essential, since it is formed from Phenylalanine in the reaction that is impaired in Phenylketonuria.

 

Additional information:

 

Most of the textbooks classify amino acids from the nutritional point of view, in two groups: essential or not essential.  Essential amino acids are considered those amino acids that can not be synthesized by an organism and so should be consumed in the diet; non essential amino acids are those amino acids that can be synthesized.  This classification is not related to the importance of the amino acids, but with the fact of them being required in the diet or not.

 

According to this classification, the essential amino acids are:

 

Arginine, Histidine, Isoleucine, Leucine, Lysine, Methionine, Phenylalanine, Threonine, Tryptophan, Valine

 

(Mnemonics:

PriVaTe TIM HALL:

 

Phenylalanine

Valine

Threonine

 

Tryptophan

Isoleucine

Methionine

 

Histidine

Arginine

Leucine

Lysine)

 

Non essential amino acids are:

Alanine, Asparagine, Aspartate, Cysteine, Glutamate, Glutamine, Glycine, Proline, Serine, Tyrosine

 

Like most facts in biology, this “black and white” classification is not 100 % accurate. Actually, some amino acids are conditionally essential or partially essential, since some “essential” amino acids, like arginine,  can be synthesized by the body. Arginine is synthesized in the urea cycle, for example, but it is considered essential since the quantity of Arginine that is synthesized is not enough during the growing process.

 

 Tyrosine is an amino acid that is synthesized in the body from Phenylalanine, that is an essential amino acid. This reaction is catalyzed by the enzyme Phenylalanine Hydroxylase, that use as cofactor reduced tetrahydobiopterine.

If Phenylalanine is deficient in the diet, then the body requires tyrosine in the diet.

 

In Phenylketonuria there is an excess of Phenylalanine, since the body can not metabolize it, but Phenylketonuria is a consequence of a deficit of Phenylalanine Hydroxylase (Classic Phenylketonuria) or a deficit of Tetrahydrobiopterin Reductase. In both cases, the organism is not able to synthesize Tyrosine from Phenylalanine, so even when there is an accumulation of Phe in these patients, it can not be used to synthesize Tyrosine.

 

In fact, some of the signs and symptoms of Phenylketonuria, like mental retardation and other neurological symptoms, have been related to the unavailability of tyrosine for the synthesis of the neurotransmitters that derive from tyrosine.

 

 

The lack of pigmentation of PKU patients, has been related also to the lack of tyrosine, since Tyrosine is a precursor of melanine also.

 

It is obvious that if Tyrosine is formed in normal persons from phenylalanine through the reaction cited above, in case that this reaction can not be produced, like in PKU, it is necessary to supplement the patient with Tyrosine, since the patient can not synthesize it, so Tyrosine becomes an essential amino acid for these patients.

 

 

About PKU and amino acids

 

 

 

 

(Q AM-06) H.C, a 4 month-old male infant, emigrated with his parents from a Latin American country to the United States a month ago. He was normal at birth but in the past several days a tremor in his extremities has appeared. Last night he presented gross twitching movements in his crib. When you examine the patient, you note a musty odor to the baby’s wet diaper.

 

Immediately you order a screening test for PKU and it results positive.

 

Besides diet restrictions, but warranting an appropriate amount of the essential amino acids, which of the following amino acids you should supplement in higher quantities than in a normal diet, since it is essential for this patient?

 

a)     Alanine

 

b)     Asparagine

 

c)      Aspartate

 

d)     Glutamate

 

e)     Phenyl alanine

 

f)       Serine

 

g)     Tyrosine

 

Answer

 

     

A: About a baby with PKU (AM-01)

Original Question

 

Answer (a)

 

Phenylalanine, per se, can follow three metabolic pathways:

 

a)     incorporation to the process of synthesis of proteins

b)     hydroxylation  to tyrosine

c)      conversion to phenyl pyruvate and derivatives like phenyl lactic and phenyl acetic.

 

The incorporation of Phenylalanine to proteins depends on the requirements in the synthesis of proteins.

 

Normally, conversion of phenylalanine to phenyl pyruvate and derivatives occurs in small quantities, since most of the phenylalanine is used in the other two metabolic processes.

 

The hydroxylation of Phenylalanine to Tyrosine is catalyzed by the enzyme Phenylalanine Hydroxylase, as represented in this graphic from the NLM:

                                         

This reaction is impaired in PKU (Phenylketonuria), due to the lack of Phenyl alanine hydroxylase or to the lack of Tetrahydrobiopteryn reductase, an enzyme necessary for supplying the reduced cofactor (TH4) required for this reaction.

 

As a consequence, Phenylalanine accumulates and it is drained to the formation of Phenylpyruvate, in a transamination reaction.  Pyruvate can be reduced to Phenyllactate or decarboxylated to Phenylacetate, in a same way that Pyruvate can be reduced to Lactate or, by decarboxylation,  form the  Acetyl group of Acetyl CoA).

 

1) Phenylalanine + alpha-ketoglutarate <——–> Phenylpyruvate + glutamate

 

2) Phenyl lactate <———— Phenylpyruvate ———————–> Phenylacetate

                          (reduction)                            (decarboxylation)

 

These compounds, which are normally produced in very small amounts, accumulate in PKU and are eliminated by urine in increased quantities, where they can be detected.

 

The name Phenylketonuria corresponds to the finding of notable quantities of phenyl pyruvate and derived metabolites in urine of the patients and the detection of the metabolites was an important tool of diagnosis of this disease before the Guthrie test made available a screening test for newborns and the detection of phenylalanine in blood gave an appropriate diagnosis tool.

 

Note: questions very similar to the former one can be found frequently in different tests. The Step 1 Content description and General information 2008 (FSMB/NBME) includes a sample question in which the compound released in urine is phenylacetic. Copyrights issues do not allow me to show the question here, but you can find it as the question number 126 in the referred document. Observe that in these kind of questions the patient usually, for some circumstance, have escaped to mandatory screening for PKU)

 

 

The following site contains useful information and several links to other sites about Phenylketonuria:

 

 

http://ghr.nlm.nih.gov/condition=phenylketonuria