Clinical cases and Situational tasks

143. Biuret reaction became negative after a while of proteins hydrolysis. What changes in the protein it specifies?

Answer: The negative biuret reaction shows that there is no native protein and indicates on the completion of hydrolysis.

143. The positive reaction with sulfosalicylic acid in urine of a patient was observed. 0,253 % of protein was detected. What does it mean? What consequences in the body can cause this condition?

Answer: The positive reaction with sulfosalicylic acid indicates on the presence of a protein in urine, and it could be caused by kidney diseases. This state can cause hypoproteinemia, the decrease of the oncotic preassure and development of edema.

144. What is molecular weigh of glutathione, if the weigh percent of sulfur in it is equal 10,42 %? What is the biological role of glutathione?

Answer. The molecular weigh of glutathione can be calculated according to proportion:

100 g of glutathione contains 10,42 g of sulfur

х g ------------------------ 32 g of sulfur

х = 307 g of glutathione

Glutathione serves as a reductant; is conjugated to drugs to make them more water soluble; is involved in amino acid transport across cell membranes (the g-glutamyl cycle); is a substrate for the peptidoleukotrienes; serves as a cofactor for some enzymatic reactions and as an aid in the rearrangement of protein disulfide bonds.

145. In a patient 10 g of urine per day is excreted. Evaluate this result.

Answer: The increased content of urea in urine can be caused by negative nitrogen balance. There is a nett loss of body protein. It reflects either a response to trauma or infection, or an intake that is inadequate to meet the need to replace tissue proteins that are turning over.

146. Laboratory analysis of the urine of a six-day infant displayed excessive concentration of phenylpyruvate and phenylacetate. Metabolism of what amino acid is disturbed in the body of this child?

Answer: Excessive concentration of phenylpyruvate and phenylacetate indicates on the development of phenylketonuria, which is an autosomal recessive metabolic genetic disorder characterized by a mutation in the gene for the hepatic enzyme phenylalanine hydroxylase, rendering it nonfunctional. This enzyme is necessary to metabolize the amino acid phenylalanine to the amino acid tyrosine. When phenylalanine hydroxylase activity is reduced, phenylalanine accumulates and is converted into phenylpyruvate (also known as phenylketone), which is detected in the urine.

147. An 81/2-month-old infant was admitted to the hospital in a coma and a temperature of 39.4°C (102.9°F). His pulse was elevated, his liver was enlarged, and an electroencephalogram was grossly abnormal. Since the infant could not retain milk given by gavage feeding, intravenous glucose was administered. He improved rapidly and came out of the coma in 24 hours. Analysis of his urine showed abnormally high amounts of glutamine and uracil, which suggested a high blood ammonium ion concentration. The laboratory confirmed this. Considering the data, which enzyme may be defective in this patient?

Answer: The patient exhibits signs of a defect in the urea cycle. The presence of elevated uracil in addition to ammonia and glutamine points to an accumulation of carbamoyl phosphate. If ornithine transcarbamoylase is deficient, carbamoyl phosphate will accumulate in the mitochondria and leak into the cytosol, providing the starting compound for the synthesis of uracil.

148. A newborn male infant was diagnosed as having phenylketonuria (PKU), and immediately placed on diet low in phenylalanine (Phe); careful compliance with the diet and frequent monitoring of the patient’s plasma Phe level resulted in the level being maintained at the lower limit of the normal range. The patient appeared to be developing normally until 4 months of age, when he developed truncal hypotonia and spasticity of the limbs. Despite being on a low-phenylalanine diet, at 5 months the patient had several grand mal (epileptic) seizures. After an abnormal Phe-loading test, the patient’s urine was found to have a markedly elevated urinary biopterin concentration. Which of enzymes is most likely deficient in this patient?

Answer: The patient, despite being put on a low-Phe diet, exhibits neurologic problems resulting from an inability to synthesize catecholamine and indoleamine neurotransmitters. This is caused by a deficiency in dihydropteridine reductase (DHPR). DHPR regenerates tetrahydrobiopterin (BH₄), which is oxidized to dihydrobiopterin by phenylalanine hydroxylase, as well as tyrosine hydroxylase and tryptophan hydroxylase (tryptophan 5-monooxygenase). If phenylalanine hydroxylase were deficient, a diet low in Phe would alleviate the effects. Since the urinary biopterin concentration is elevated, a deficiency in GTP cyclohydrolase I is eliminated because that is an enzyme in the biosynthetic pathway of BH₄. Phe hydroxylase, Tyr hydroxylase, and Trp hydroxylase activities are low because of a lack of BH₄.

149. A 1-year-old girl is brought to her pediatrician’s office with concerns about her development. The mother reports that the baby is not achieving the normal milestones for a baby of her age. She also reports an unusual odor to her urine and some areas of hypopigmentation on her skin and hair. On exam, the girl is noted to have some muscle hypotonia and microcephaly. The urine collected is found to have a “mousy” odor. What is the most likely diagnosis? What is the biochemical basis of the hypopigmented skin and hair?

Answer: Likely Diagnosis: Phenylketonuria (PKU). Biochemical basis of hypopigmentation: phenylalanine is competitive inhibitor of tyrosinase (key enzyme in melanin synthesis) Elevated phenylalanine can be caused by a variety of different enzyme deficiencies resulting in impaired conversion of phenylalanine to tyrosine. The most common deficiency is in phenylalanine hydroxylase (autosomal recessive) resulting in the classic picture of PKU. Two other enzyme deficiencies leading to PKU include dihydropteridine reductase and 6-pyruvoyl-tetrahydropterin synthase, an enzyme in the biosynthetic pathway of tetrahydrobiopterin. With PKU, the baby appears normal at birth but then fails to reach normal developmental milestones. If unrecognized, the child will develop profound mental retardation and impairment of cerebral function. A mousy odor of the skin, hair, and urine can often be detected clinically. Treatment consists of dietary modifications with limitation of phenylalanine intake and supplementation of tyrosine. The diagnosis of PKU and initiation of diet modification needs to be implemented prior to 3 weeks of age to prevent mental retardation and the other classic signs of PKU.

150. A 1-year-old girl presents at your clinic the day after you saw the 3-month-old boy. The symptoms are the same so you order a test on phenylalanine hydroxylase to confirm your diagnosis of phenylketonuria. To your surprise the phenylalanine hydroxylase activity is well within the normal range. Which of enzymes might you check next to support your diagnosis?

Answer: The correct response is dihydropteridine reductase. This enzymereduces dihydrobiopterin to tetrahydrobiopterin the obligate electron donor for phenylalanine hydroxylase. Tyrosinase is the first enzyme on the pathway to melanin. Dopamine hydroxylase and tyrosine transaminase are enzymes on other tyrosine metabolic tracts. Homogentisic acid oxidase is an enzyme on the pathway of tyrosine to fumarate and acetoacetate.