Lecture 16

Question 1

diverse structural properties of ________ are critical fo modulating receptor/ligand binding, affecting cell function and tissue morphogenesis

Answer 1

glucosaminoglycans

Question 2

Any disruption of the ability of the cell to perform critical biochemical reactions involved in the process of converting food to energy on a cellular level

Answer 2

metabolic disease

Question 3

patients with SLOS with cholesterol levels greater than or equal to 1.7 mmol/L _______

Answer 3

had milder features and were diagnosed at 9 months to 25 years of age

Question 4

A family of highly sulfated, complex linear polysaccharides having a variety of biological roles:Heparin/heparan sulfate, Chondroitin sulfate/dermatan sulfate, Keratan sulfate, Hyaluronan

Answer 4

Glycosaminoglycans (GAG)

Question 5

characterized by distinct clustering of phenotypes that is dependent on defective enzyme in the process of assembly

Answer 5

N-glycosylation

Question 6

process by which sugar ‘trees’ (glycans) are created, altered and chemically attached to certain proteins or fats (lipids).

Answer 6

glycosylation

Question 7

Mutations in any of the 12 genes responsible for _____ all lead to a similar phenotype.

Answer 7

O-linked glycosylation

Question 8

Disorder of cholesterol metabolism; Caused by mutation in the DHCR7 gene; Encodes dehydrocholesterol delta reductase; Elevated cholesterol precursors, decreased cholesterol; Multiple anomalies (cardiac, urogenital, digit, renal, pulmonary), dysmorphic face, growth deficiency, mental retardation, including autism, epilepsy, aggression, self-mutilation

Answer 8

SMITH-LEMLI-OPITZ SYNDROME (SLOS)

Question 9

separate molecules such as proteins or enzymes based upon their electrical charge

Answer 9

isoelectric focusing (IEF)

Question 10

Gingival hyperplasia, delayed tooth eruption, malocclusion, mandibular dysplasia, radiolucent lesions in the jaws, and condylar defects.

Answer 10

MPS I (Hurler syndrome) & MPS II (Hunter syndrome)

Question 11

patients with SLOS with cholesterol levels less than or equal to 0.35mmol/L _______

Answer 11

died

Question 12

simple monosaccharide of nuclear transcription factors and complex branched polysaccharides (GAGs) on cell surface receptors are types of

Answer 12

protein glycosylation

Question 13

cell membranes, myelin (axonal), bile acids, steroid hormones, SHH signaling are all functions of

Answer 13

cholesterol

Question 14

Group of 7 distinct disorders characterized by a deficiency in 1 of 11 enzymes involved in breakdown of GAGs; Overall prevalence range of 1.9 to 4.5 per 100,000 live births; Characterized by lysosomal storage of GAGs; The progressive accumulation of GAGs results in skeletal deformities, poor joint mobility, severe growth deficit, coarse facial features, and enlarged organs

Answer 14

MUCOPOLYSACCHARIDOSES (MPS)

Question 15

due to importance of O-glycosylation for the anchoring function of dystroglycan

Answer 15

muscular dystrophy

Question 16

allows for early treatment or dietary intervention to prevent/manage/delay symptoms [phenylketonuria (PKU), hypothyroidism, galactosemia, sickle cell disease, cystic fibrosis (CF)]

Answer 16

newborn metabolic screening

Question 17

refers to amide bond (beta-conformation) formed between GlcNAc (acetylglucosamine) and the amino acid,Asparagine (Asn:N), in a protein.Occurs within the endoplasmic reticulum (ER).

Answer 17

N-linked glycosylation

Question 18

simple blood test to analyze the glycosylation of transferrin, electrospray ionization-mass spec used to detect abnormal transferrin, enzyme activity assay, molecular genetic testing is needed for confirmation

Answer 18

clinical testing for CDG

Question 19

one of the major post-translational modifications

Answer 19

protein glycosylation

Question 20

severe cases of SLOS present with features on the _______ spectrum

Answer 20

holoprosencephaly (HPE)

Question 21

T/F: Early detection may improve outcome of patients as cholesterol supplementation can improve symptoms

Answer 21

True

Question 22

T/F: Metabolic disease is not typically heritable

Answer 22

False

Question 23

carbohydrates bound to a protein backbone through hydroxyl residues (eg. on Ser, Thr, Tyr). Occurs mostly in ER & Golgi.

Answer 23

O-linked glycosylation

Question 24

______ impacts protein folding, distribution, stability, and activity in ER

Answer 24

protein glycosylation

Question 25

up to 80 sugars linked to protein in ER and Golgi, subsequently sulfated in Golgi, further modulating properties of the protein, extracellular gel giving tensile strength and elasticity and resists compressive force

Answer 25

glycosaminoglycans

Question 26

genetics, nutrition, gender, age, environment, cultural, occupation are all influencing and interacting factors of ____

Answer 26

metabolic disease

Question 27

The pattern of glycosylation is often ________ due to differential expression of the genes encoding the respective enzymes

Answer 27

cell-type specific

Question 28

HPE most commonly caused by defects in the _______ pathway, which is known to be regulated by cholesterol

Answer 28

Sonic Hedgehog (SHH)

Question 29

characterized by variably dysmorphic features like prominent forehead, dysplastic ears and large ear lobules, thin upper lip, long philtrum, prominent jaw, prominent nose and anteverted nares, and high arched palate

Answer 29

congenital disorders of glycosylation

Question 30

mutations in each gene required for ______ do not all give the same phenotype - rather, they group in clusters.

Answer 30

N-linked glycosylation

Question 31

a secreted ligand, has 2 co-receptors, and signaling primarily occurs in primary cilia

Answer 31

Sonic Hedgehog (SHH)

Question 32

many metabolic diseases affect ____ and _____

Answer 32

bone, cartilage

Question 33

Multiple dentigerous cysts, macroglossia, fibrous gingival hyperplasia, generalized bone rarefactions, expanded marrow spaces, cortical wear, osteosclerosis, root resorption, demineralization of the symphysis region, impairment of TMJ, impacted teeth, and morphologic alterations in nasal cavity and maxillary sinuses.

Answer 33

MPS VI (Marateaux-Lamy syndrome)

Question 34

Obliteration of pulp chambers and irregular root canals.

Answer 34

MPS III (Sanfilippo syndrome)

Question 35

the pattern of glycosylation is often ______ due to differential expression of the genes encoding the respective enzymes

Answer 35

cell type-specific

Question 36

Enamel defects (1 ̊ & 2 ̊ dentition), with generalized loss of tooth structure.

Answer 36

MPS IV (Morquio syndrome)

Question 37

major pathway coordinating embryonic morphogenesis and patterning, particularly the brain and the midline of the craniofacial complex.

Answer 37

SHH signaling