b) Briefly justify the following statement:
• Tyrosine becomes essential amino acids for PKU patients.
• Homocystinuria is a high risk factor for atherogenesis.
• Occurrence of cataracts is a common symptom in galactosemia.
• Large pale cells are seen in Gaucher's disease.
ANS- *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.
* Homocysteine is a sulphurated amino acid which, at high plasma concentrations, predisposes to thrombosis and induces focal arteriosclerosis. These characteristics have been established both in patients with homocystinuria, a genetic disease in which homocysteine accumulates in the blood, and in animals submitted to intravenous infusions of this amino acid. Many recent publications have addressed the problem of whether mild increases in plasma homocysteine predisposed to the development of the usual forms of atherosclerosis. Transverse epidemiological studies have established a correlation between homocysteine levels and atherosclerosis at all its vascular localisations, coronary, carotid and lower limb. Multivariate analysis in several prospective studies have shown plasma homocysteine to be an independent risk factor for cerebrovascular accidents and myocardial infarction. Causes of mild increases in plasma homocysteine are usually dietetic deficiencies in folic acid, vitamin B6 or B12, or genetic by mutation of the methylene-tetrahydrofolate reductase. Renal failure is also associated with a high risk in plasma homocysteine levels. However, the toxicity of homocysteine to the arterial wall at slightly elevated concentration remains speculative.
*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.
* Galactosemia is an inborn error of carbohydrate metabolism first described by von Reuss1 a half a century ago. Sporadic reports of the disorder are found in the literature since that time, and during the past decade, probably because of earlier recognition and diagnosis, such reports have appeared with increasing frequency. The occurrence of cataracts is one of the common features of the disease, and it is the purpose of this paper to give a longrange follow-up of the eye findings in a relatively large group of cases.
Clinical Findings Clinically, infants with galactosemia appear normal at birth, but signs and symptoms appear within a few days or weeks at most. Presenting symptoms are usually vomiting, lethargy, fever, and failure to gain weight. Icterus, ascites, peripheral edema, hepatomegaly, and splenomegaly are among the physical findings.2 Cataracts and mental retardation may be recognized as early as 4 to 8 weeks
* Many inherited disorders of metabolism involve enzymes in degradation pathways. A deficiency of such an enzyme can lead to accumulation of intermediate metabolites that accumulate as storage products in cells, as seen here with Gaucher disease involving spleen. The large pale cells contain an accumulated storage product from lack of the glucocerebrosidase enzyme.
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