Question 1

You are treating a 4-year-old child who has been afflicted with recurrent infections. The child exhibits retarded development, weakness, and weight loss. Physical examination also shows absent tonsils and blood work reveals a lack of lymphocytes. These signs and symptoms are typical of severe combined immunodeficiency syndrome. Which of the following compounds would be expected to be elevated in the blood of this patient?

A) bilirubin
B) cytosine
C) deoxyadenosine
D) deoxythymidine
E) xanthine

deoxyadenosine

Accepted Answer

In severe combined immunodeficiency syndrome (SCID), particularly the adenosine deaminase (ADA) deficiency type, there is an accumulation of deoxyadenosine because ADA is responsible for its breakdown. This accumulation is toxic to lymphocytes, leading to the immunodeficiency observed.  Severe combined immunodeficiency disease (SCID) is a disorder related to defects in the activity of the purine nucleotide catabolism enzyme, adenosine deaminase (ADA). In ADA deficiency there is an elevation in the level of adenosine and 2′-deoxyadenosine in the blood and 2′-deoxyadenosine levels in the urine are also elevated. The consequences of the elevations in these two ADA substrates are impaired lymphocyte differentiation, function, and viability, which results in lymphopenia and severe immunodeficiency. Increases in 2′-deoxyadenosine, through the action of ubiquitous nucleoside phosphorylases, results in dramatic increases in cellular dATP pools. The consequences of increased dATP pools are an inhibition of ribonucleotide reductase (RR), the enzyme responsible for generating deoxyribonucleotides (necessary for DNA replication) from ribonucleotides.

Question 2

You are examining a 7-year-old male child who exhibits delayed motor development, overexaggerated reflexes, and spasticity. In addition, the boy has a tendency to chew his lips and fingers often causing tissue damage and bleeding. He also has painful, swollen, and inflamed joints. The most likely diagnosis in this case is Lesch-Nyhan syndrome. Which of the following compounds would be expected to be elevated in the urine of this patient?

A) adenosine
B) guanine
C) hypoxanthine
D) uric acid
E) xanthine

uric acid

Accepted Answer

Lesch-Nyhan syndrome results from deficiencies in hypoxanthine-guanine phosphoribosyltransferase (HGPRT). HGPRT is a purine nucleotide salvage enzyme that converts guanine to GMP and hypoxanthine to inosine 5'-monophosphate (IMP). Loss of this salvage enzyme results in increased rates of purine nucleotide catabolism whose end product is uric acid. Lesch-Nyhan syndrome is caused by a deficiency in the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT), leading to an overproduction of uric acid. This results in elevated levels of uric acid in the urine.

Question 3

You are examining a 5-year-old male child who has been exhibiting a tendency to bite his lower lip to
The point of bleeding as well as chewing on his fingertips. Physical examination demonstrates swollen tender joints. These symptoms and lab results are indicative of a deficiency in HGPRT. Given this enzyme deficiency, which of the following compounds would be expected to be elevated in the serum of this patient?

A) bilirubin
B) cytosine
C) glycine
D) orotate
E) xanthine

xanthine

Accepted Answer

A deficiency in HGPRT is the cause of Lesch-Nyhan syndrome. HGPRT is a purine nucleotide salvage enzyme that converts guanine to GMP and hypoxanthine to IMP. Reduced activity of this enzyme results in increased rates of purine nucleotide catabolism due to the inability to effectively carry out purine salvage. The reduced rate of hypoxanthine salvage by HGPRT will result in increased production if xanthine catalyzed by the xanthine oxidase reaction. In HGPRT deficiency, as seen in Lesch-Nyhan syndrome, there is an accumulation of uric acid due to the inability to salvage hypoxanthine and guanine, leading to increased levels of xanthine and uric acid in the serum.

Question 4

Certain nucleic acids harbor significant free energy that can be released and coupled to the synthesis of biological molecules. Which of the following represents a nucleic acid form containing the greatest amount of free energy?

A) adenine
B) adenosine
C) adenosine monophosphate
D) adenosine diphosphate
E) adenosine triphosphate

Accepted Answer

Adenosine triphosphate (ATP) contains three phosphate groups, and the bonds between these phosphates (particularly the terminal phosphate bond) store a significant amount of free energy. When ATP is hydrolyzed to ADP or AMP, this energy is released and can be used to drive various biological processes.  The high free energy in nucleic acids is imparted by the formation of phosphate bonds. The nucleobase and nucleosides do not contain sufficient energy to drive biosynthetic processes. The phosphate in a monophosphate nucleotide is linked via an ester bond to the ribose. The di- and tri-phosphates of nucleotides are linked by anhydride bonds. Acid anhydride bonds have a high ΔG0′ for hydrolysis imparting upon them a high potential to transfer the phosphates to other molecules. Since the triphosphate nucleotide contains 2 phosphoanhydride bonds, it is this form that has the greatest level of free energy.

Question 5

When glucagon binds to its receptors on the surface of adipose tissue, it activates a signaling cascade leading to the release of free fatty acids that can be utilized by the liver and other peripheral tissues for energy production. Which of the following is the correct nucleic acid involved in the triggering of this cascade?

A) ATP
B) cAMP
C) cGMP
D) GTP
E) xanthine

Accepted Answer

cAMP (cyclic adenosine monophosphate) is the second messenger involved in the signaling cascade triggered by glucagon binding to its receptor, leading to the activation of protein kinase A and subsequent release of free fatty acids.  Glucagon binds to plasma membrane receptors coupled through a G-protein that activates adenylate cyclase. Adenylate cyclase generates cAMP from ATP and the resultant increases in cAMP in turn activate cAMP-dependent protein kinase, PKA. Activation of PKA leads to increased fatty acids release from triglycerides stored in adipose tissue.

Deck 4: Nucleic Acids