Question 1

I-cell disease (also identified as mucolipidosis type II) is characterized by the presence of inclusion bodies in fibroblasts (hence the derivation of the term I-cell), severe psychomotor retardation, corneal clouding, and dysostosis multiplex. These symptoms arise from a defect in the targeting of lysosomal enzymes due to an inability to carry out which of the following processes?

A) produce mannose-6-phosphate modifications in lysosomal enzymes
B) recycle the lysosomal receptor for mannose 6-phosphate present on lysosomal enzymes
C) remove mannose 6-phosphates from lysosomal enzymes prior to their transport to the lysosomes
D) synthesize the mannose 6-phosphate receptor found in lysosomes
E) transport mannose-6-phosphate receptors to lysosomes

produce mannose-6-phosphate modifications in lysosomal enzymes

Accepted Answer

I-cell disease is caused by a defect in the enzyme that adds mannose-6-phosphate to lysosomal enzymes, which is necessary for their proper targeting to lysosomes.  Enzymes that are destined for the lysosomes (lysosomal enzymes) are directed there by a specific carbohydrate modification. During transit through the Golgi apparatus, a residue of GlcNAc-1-phosphate (GlcNAc-1-P) is added to the carbon-6 hydroxyl group of one or more specific mannose residues that have been added to these enzymes. A specific Man-6-P receptor (MPR) is present in the membranes of the Golgi apparatus. Binding of Man-6-P to this receptor targets proteins to the lysosomes.

Question 2

You are treating an 8-month-old female infant brought in by her parents because of seizures. Physical examination indicates microcephaly, microphthalmia with retinal detachment. and severe mental retardation. You suspect these symptoms are associated with a specific gene defect and order a test for the presence of mutations in α-dystroglycan. Test results are positive. A defect in which of the following, related to α-dystroglycan processing, is most likely in this patient?

A) N-glycosylation
B) O-GlcNAcylation
C) O-glycosylation mucin type
D) O-mannosylation

O-mannosylation

Accepted Answer

The symptoms and positive test for α-dystroglycan mutations suggest a defect in O-mannosylation, which is crucial for proper α-dystroglycan function and is associated with congenital muscular dystrophies.  O-mannosylation has been identified on α-dystroglycan (α-DG) from nerve and muscle, chondroitin sulfate proteoglycans and total glycopeptides from brain tissue. Clinically, O-mannosylation of α-DG is the most significant as evidenced by the constellation of symptoms that result from defects in the processes of O-mannosylation. Defective O-mannosylation is associated with a group of autosomal recessive muscular dystrophies termed congenital muscular dystrophies (CMDs). In addition to muscle dysfunction, these CMDs are also associated with variable brain and ocular abnormalities.

Question 3

You are studying the responses of adipocytes in culture to insulin following addition of a test compound. In the absence of the compound, addition of insulin to your culture system results in increased glucose uptake. However, following addition of the test compound, the effects of insulin on glucose uptake are severely impaired. Analysis of components of the insulin-signaling pathway indicates that addition of the compound results in a dramatic increase in O-GlcNAcylation. Your test compound is likely to be most highly related to which of the following?

A) CTP
B) glucosamine
C) glucose
D) glucose-6-phosphate
E) UTP

glucosamine

Accepted Answer

Glucosamine is a precursor for the synthesis of UDP-GlcNAc, which is involved in O-GlcNAcylation, a process that can interfere with insulin signaling and glucose uptake.  Numerous proteins involved in insulin signaling and the downstream targets of these signaling cascades have been shown to be O-GlcNAcylated. With respect to insulin receptor signaling proteins, IRS-1, PI3K, PKB/Akt, PDK1, and GSK-3β are all known to be O-GlcNAcylated. These modifications have all been observed in adipocytes, which are a major target for the actions of insulin. It is possible for glucosamine to enter the HBP directly by conversion to glucosamine-6-phosphate (GlcN6P) via the action of hexokinase. This reaction bypasses the rate-limiting step of the pathway catalyzed by GFAT and will lead to increased O-GlcNAcylation of proteins.

Question 4

You are examining a 2-year-old girl brought in by her parents because they are concerned about her lack of any type of talking and she seems unusually clumsy. History reveals that the child has had numerous upper respiratory infections over the past 6 months. You suspect the child is suffering from a particular form of a lysosomal storage disease. Genetic testing reveals a missense mutation in the N-aspartyl-β-glucosaminidase gene. This child is most likely suffering from which of the following defects in glycoprotein metabolism?

A) aspartylglucosaminuria
B) fucosidosis
C) leukocyte adhesion deficiency syndrome II (LAD II)
D) Sandhoff disease
E) sialidosis

Accepted Answer

Aspartylglucosaminuria is a lysosomal storage disease caused by a deficiency in the enzyme N-aspartyl-β-glucosaminidase, leading to the accumulation of glycoasparagines. The symptoms and genetic mutation described match this condition. Aspartylglucosaminuria belongs to a family of disorders identified as lysosomal storage diseases. This disorder is characterized by the lysosomal accumulation of glycoasparagines, primarily aspartylglycosamine. These glycoasparagines accumulate in the lysosomes as a consequence of defects in the lysosomal hydrolase, N-aspartyl-β-glucosaminidase. The hallmark symptom of aspartylglucosaminuria is a global delay in psychomotor development that begins between 2 and 4 years of age. There is a period of frequent upper respiratory infections followed by delayed speech and physical clumsiness. The disorder in speech development is a cardinal sign of mental retardation and is usually the first indication to parents that there is something amiss with their child.

Question 5

E-selectin is a member of the lectin family of carbohydrate-binding proteins. The cell surface presentation of E-selectin is required for which of the following processes?&#10;A) ability of monocytes to bind and phagocytose cholesterol&#10;B) activation of platelet adhesion to subendothelial extracellular matrix proteins&#10;C) binding of platelets to endothelial cells&#10;D) binding of monocytes to platelets&#10;E) interaction of neutrophils with endothelial cells

Accepted Answer

E-selectin is involved in the interaction of neutrophils with endothelial cells, facilitating their adhesion and migration during the inflammatory response. The selectins are subtype IV C-type lectins defined by the presence of the C-type lectin CRD, an epidermal growth factor-like domain, and a variable number of complement regulatory proteinlike repeat domains. The selectins are also members of the cell adhesion family of proteins. Each selectin is tethered to the plasma membrane via a single transmembrane domain. A major function of the selectins is the recruitment of neutrophils to sites of inflammation.

Question 6

Patients with classic paroxysmal nocturnal hemoglobinuria (PNH) have clinical evidence of intravascular hemolysis typified by reticulocytosis, abnormally high concentration of serum lactate dehydrogenase, indirect bilirubin, and abnormally low concentration of serum haptoglobin. These symptoms are due to a lack of being able to carry out which of the following posttranslational modifications?

A) glipiated linkage
B) mannose 6-phosporylation
C) N-linked glycosylation
D) O-linked glycosylation
E) prenylation

Accepted Answer

Patients with PNH have a deficiency in the GPI anchor, which is a type of glipiated linkage, due to mutations in the PIGA gene. This deficiency leads to the absence of protective proteins on the surface of red blood cells, causing hemolysis.  Many membrane-associated glycoproteins belong to neither the peripheral nor the transmembrane class. These glycoproteins are tethered to the outer leaflet of the plasma membrane via a glycosylphosphatidylinositol linkage to their C-termini. This type of membrane attachment is referred to as a GPI linkage and the glycoproteins are termed glypiated proteins. One clinically important glypiated protein is the glycoprotein present on the surface of erythrocytes, that is, decay-accelerating factor (DAF; also known as CD55 = cluster of differentiation protein 55). The normal function of DAF is to prevent erythrocyte lysis by complement

Question 7

A 4-year-old boy presents with persistent leukocytosis. Patient history reveals that the boy has suffered from recurrent infections. On physical examination, the physician notes severe growth and mental retardation. An additional feature of this child is that he harbors the rare Bombay (hh) blood type at the ABO locus. These findings are consistent with the child suffering from which of the following disorders?

A) congenital disorder of glycosylation Ia (CDG Ia)
B) I-cell disease
C) leukocyte adhesion deficiency syndrome II (LAD II)
D) pseudo-Hurler polydystrophy
E) Tay-Sachs disease

Accepted Answer

Leukocyte adhesion deficiency syndrome II (LAD II) is characterized by persistent leukocytosis, recurrent infections, growth and mental retardation, and the rare Bombay blood type due to a defect in fucose metabolism affecting blood group antigen expression.  The child is suffering from LAD II, which is a disease that belongs to the class of disorders referred to as primary immunodeficiency syndromes. Symptoms of LAD II are characterized by unique facial features, recurrent infections, persistent leukocytosis, defective neutrophil chemotaxis, and severe growth and mental retardation. The genetic defect resulting in LAD II is in the pathway of fucose utilization leading to loss of fucosylated glycans on the cell surface. An additional feature of LAD II is that individuals harbor the rare Bombay (hh) blood type at the ABO locus as well as lack the Lewis blood group antigens. The recurrent infections seen in LAD II patients are the result of the defective neutrophil function. Neutrophils are involved in innate immunity responses to bacterial infection. To carry out their role in host defense mechanisms, neutrophils must adhere to the surface of the endothelium at the site of inflammation, which is an event mediated by cell surface adhesion molecules. The selectin family (E-, L-, and P-selectins) of animal lectins are necessary to mediate the initial process of neutrophil adherence to the endothelium. The selectins recognize sialylated fucosylated lactosamines typified by the Lewis X antigen.

Question 8

A 6-month-old infant presents with failure to thrive, obvious developmental delay, abnormal skeletal development, coarse facial features, and restricted joint movement. Cellular and biochemical analysis indicates the infant is suffering from a defect in protein modification. These clinical symptoms are most indicative of which of the following disorders?

A) congenital disorder of glycosylation Ia (CDG Ia)
B) I-cell disease
C) leukocyte adhesion deficiency syndrome II (LAD II)
D) pseudo-Hurler polydystrophy
E) Tay-Sachs disease

Accepted Answer

The symptoms described are characteristic of I-cell disease, which is caused by a defect in the modification of lysosomal enzymes, leading to their improper targeting and accumulation of undegraded substrates.  I-cell disease (also called mucolipidosis II α/β, ML-II α/β) is an autosomal recessive disorder that results as a consequence of defective targeting of lysosomal hydrolases to the lysosomes. The disorder is so called because fibroblasts from afflicted patients contain numerous phase-dense inclusion bodies in the cytosol. I-cell disease is characterized by severe psychomotor retardation that rapidly progresses. leading to death between 5 and 8 years of age. I-cell patients exhibit coarse facial features, craniofacial abnormalities, and severe skeletal abnormalities. Additional clinical symptoms of I-cell disease include hepatomegaly, cardiomegaly, umbilical hernias, and recurrent upper respiratory infections.

Question 9

A percentage of the population manifests the ABO blood group antigens in saliva and other mucous secretions and are thus referred to as "secretors," whereas those that do not are termed "nonsecretors." The difference between these 2 populations results from which of the following?

A) ABO antigens present on circulating lipids
B) ABO antigens present on circulating proteins
C) inappropriate activation of the ABO-specific glycosyltransferases in mucus-secreting tissues
D) mild hemolysis that releases cellular ABO antigens
E) presence of a mutant glycosyl hydrolase, which releases the ABO antigens from cell surfaces

Accepted Answer

The ABO blood group antigens are the carbohydrate moieties of glycolipids on the surface of cells as well as the carbohydrate portion of serum glycoproteins. When the ABO carbohydrates are associated with protein in the form of glycoproteins, they are found in the serum and are referred to as the secreted forms. Some individuals produce the glycoprotein forms of the ABO antigens while others do not. This property distinguishes secretors from nonsecretors, a property that has forensic importance such as in cases of rape.

Question 10

The correct targeting of newly synthesized hydrolytic enzymes to the lysosomes requires which of the following modifications?&#10;A) attachment of mannose 6-phosphate to the enzymes&#10;B) g-Carboxylation of glutamate residues in the enzymes&#10;C) O-linkage of carbohydrate to the enzymes&#10;D) prenylation of the enzymes&#10;E) proteolytic activation following transport to the lysosome

Accepted Answer

The attachment of mannose 6-phosphate to enzymes is crucial for their recognition and transport to lysosomes. This modification occurs in the Golgi apparatus and is essential for the proper targeting of lysosomal enzymes.  Enzymes that are destined for the lysosomes (lysosomal enzymes) are directed there by a specific carbohydrate modification. During transit through the Golgi apparatus, a residue of GlcNAc-1-phosphate (GlcNAc-1-P) is added to the carbon-6 hydroxyl group of one or more specific mannose residues that have been added to these enzymes. A specific Man-6-P receptor (MPR) is present in the membranes of the Golgi apparatus. Binding of Man-6-P to this receptor targets proteins to the lysosomes.

Question 11

You are examining a 2-year-old child who has begun having trouble walking and stumbles and falls frequently. Additional manifesting symptoms are developmental delay, muscle weakness, and speech and vision impairment. Muscle biopsy results indicate the patient has a deficiency in functional α-dystroglycan. The clinical signs in this patient would most likely be associated with a defect in which of the following pathway?

A) addition of sialic acid residues to α-dystroglycan
B) O-mannosylation of α-dystroglycan
C) processing of the lipid-linked oligosaccharide used in N-glycosylation of α-dystroglycan
D) regulation of the hexosamine biosynthesis pathway such that α-dystroglycan is abnormally O-GlcNAcylated
E) synthesis of O-linked hydroxylysine residues in collagens associated with α-dystroglycan

Accepted Answer

The answer of You are examining a 2-year-old child who...

Question 12

Which of the following carbohydrate-modified molecules are enriched in the viscous gel that lines the pulmonary airways?&#10;A) GlcNAcylated glycoproteins&#10;B) glycosphingolipids&#10;C) N-linked glycoproteins&#10;D) O-linked glycoproteins&#10;E) O-mannosylated glycoproteins

Accepted Answer

The answer of Which of the following carbohydrate-modified molecules are...

Question 13

The hexosamine biosynthesis pathway (HBP) is regulated at the level of the reaction catalyzed by glutamine:fructose-6-phosphate aminotransferase 1 (GFAT). However, excess availability of which of the following can lead to unregulated O-GlcNAc synthesis?

A) fructose 1-phosphate
B) glucosamine
C) glucose
D) glucose 6-phosphate
E) glutamine

Accepted Answer

The answer of The hexosamine biosynthesis pathway (HBP) is regulated...

Question 14

You are studying the consequences of carbohydrate modification of proteins in hepatocyte cultures. Your studies reveal that addition of high levels of glucose to the culture system results in modification and activation of the transcription factor PGC-1α, leading to an increased rate of gluconeogenesis. Which of the following is the most likely modification that results in the observed activation of PGC-1α?

A) N-glycosylation
B) O-GlcNAcylation
C) O-glycosylation mucin type
D) O-mannosylation

Accepted Answer

The answer of You are studying the consequences of carbohydrate...

Question 15

The lectins are proteins that recognize and bind to specific types of carbohydrate structures displayed on other proteins and/or lipids. Perhaps the most important homeostatic function of the animal lectins is their roles in the regulation of immune responses and autoimmunity. Which of the following classes of lectins have a member that exhibits potent anti-inflammatory effects due to its ability to induce apoptosis in activated T cells?

A) collectins
B) ficolins
C) galectins (S-type lectins)
D) pentraxins
E) siglecs (I-type lectins)

Accepted Answer

The answer of The lectins are proteins that recognize and...

Question 16

You are studying the process of protein glycosylation utilizing cells isolated from a breast cancer tumor. Analysis of the cells reveals that they are incapable of incorporating glucose into glycoproteins. Which of the following is most likely not synthesized, thereby preventing glycosyltransferases from incorporating glucose into the oligosaccharide portion of glycoproteins in these cells

A) AMP 1-glucose
B) CDP 6-glucose
C) glucose 1-phosphate
D) glucose 1,6-bisphosphate
E) UDP 1-glucose

Accepted Answer

The answer of You are studying the process of protein...

Question 17

Which of the following features of the carbohydrate portion of glycoproteins determines their uptake into lysosomes?&#10;A) multiple galactose residues&#10;B) N-acetylneuraminic acid residues&#10;C) O-linked oligosaccharides&#10;D) terminal fucose residues&#10;E) terminal mannose 6-phosphate residues

Accepted Answer

The answer of Which of the following features of the...

Question 18

An oligosaccharide unit is transferred from dolichol pyrophosphate to an asparagine moiety of a protein in which of the following structures?&#10;A) endosomes&#10;B) lysosomes&#10;C) mitochondria&#10;D) nuclei&#10;E) rough endoplasmic reticulum

Accepted Answer

The answer of An oligosaccharide unit is transferred from dolichol...

Question 19

A 6-month-old boy is brought to his pediatrician by his mother for a follow-up examination. When born, the infant had a low birth weight, coarse facial features, and restricted motion of the extremities. Serum and urine analysis at this time indicated the presence of lysosomal enzyme activity. Physical examination today shows psychomotor retardation and hepatomegaly. A biopsy of skin is taken and analysis of the fibroblasts indicates that they contain multiple intracellular cytoplasmic inclusions. A deficiency in which of the following posttranslational modifications is most likely present in this infant?

A) acetylation of galactosamine
B) acetylation of glucosamine
C) phosphorylation of galactose
D) phosphorylation of mannose
E) phosphorylation of sialic acid

Accepted Answer

The answer of A 6-month-old boy is brought to his...

Question 20

You are studying the processes of glycoprotein synthesis using a cell culture system. Your experiments are focused on the attachment of oligosaccharides to asparagine residues in proteins as they transit the ER. Your experiments detect that the cells you are using are incapable of the initial transfer of nucleotide-activated sugars. Given these results, which of the following is most likely deficient in these cells?

A) arachidonic acid
B) asparagine
C) dolichol pyrophosphate
D) glucose 6-phosphate
E) serine

Accepted Answer

The answer of You are studying the processes of glycoprotein...

Deck 38: Glycoproteins