D. In purine nucleotide synthesis, the ring system is first constructed and then attached to ribose 5-phosphate.
E. Oxypurinol inhibits the amidotransferase that initiates degradation of the purine ring system.
F. Partial or complete enzymic deficiencies in the salvage of purine bases are characterized by hyperuricemia.
Q2. Purines are one type of nitrogenous base found in nucleotides. Pyrimidines are the other. Which of the following statements is true of the pyrimidines?
A. Carbamoyl phosphate synthetase I is the regulated enzymic activity in pyrimidine ring synthesis.
B. Methotrexate decreases synthesis of the pyrimidine nucleotide thymidine monophosphate.
C. Orotic aciduria is a pathology of pyrimidine degradation.
D. Pyrimidine nucleotide synthesis is independent of 5-phosphoribosyl-1pyrophosphate (PRPP).
Q3. IR is subsequently shown to have a form of PRPP synthetase that shows increased enzymic activity. Why does this result in hyperuricemia?
Case 8: No Bowel Movement
Patient Presentation: DW is a 48-hour-old female who has not yet had a bowel movement.
Focused History: DW is the full-term product of a normal pregnancy and delivery. She appeared normal at birth. DW is the first child of parents of Northern European ethnicity. The parents are both in good health, and their family histories are unremarkable.
Pertinent Findings: DW has a distended abdomen. She recently vomited small amounts of bilious (green-colored) material.
Diagnosis: Meconium ileus (obstruction of the ileum by meconium, the first stool produced by newborns) was confirmed by abdominal x-rays. About 98% of full-term newborns with meconium ileus have cystic fibrosis (CF). Diagnosis of CF was subsequently confirmed with a chloride sweat test.
Treatment: The ileus was successfully treated nonsurgically. For management of the CF, the family was referred to the CF center at the regional children’s hospital.
Prognosis: CF is the most common life-limiting autosomal-recessive disease in Caucasians.
Case-Related Questions: Choose the ONE best answer.
Q1. CF is the result of mutations to the gene that encodes the CF transmembrane conductance regulator (CFTR) protein that functions as a chloride channel in the apical membrane of epithelial cells on a mucosal surface. Which of the following statements concerning CF is correct?
A. Clinical manifestations of CF are the consequence of chloride retention with increased water reabsorption that causes mucus on the epithelial surface to be excessively thick and sticky.
B. Excessive pancreatic secretion of insulin in CF commonly results in hypoglycemia.
C. Genetic testing for CF may involve the use of a set of probes for the most common mutations, a technique known as restriction fragment length polymorphism analysis.
D. Some mutations result in premature degradation of the CFTR protein through tagging with ubiquinone followed by proteasome-mediated proteolysis.
E. The most common mutation, ∆F508, results in the loss of a codon for phenylalanine (F) and is classified as a frameshift mutation.
Q2. The CFTR protein is an intrinsic plasma membrane glycoprotein. Targeting of proteins destined to function as components of membranes:
A. includes transport to and through the Golgi.
B. involves an amino-terminal signal sequence that is retained in the functional protein.
C. occurs after the protein has been completely synthesized (that is, posttranslationally).
D. requires the presence of mannose 6-phosphate residues on the protein. Q3. Why might steatorrhea be seen with CF?
Case 9: Elevated Ammonia