EXAM 2 STARTS: Metabolic Disease and the Maxofacial Complex- Guest lecture Flashcards
What is metabolic disease
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
what is affected by metabolic disease
processing, transport, or absorption of proteins, carbohydrates, or lipids
what are the influencing factors of metabolic disease
-genetics
-nutrition
-gender
-age
-environment
-cultural
-occupation
what metabolic diseases are screened for prenatally
phenylketonuria (PKU), hypothyroidism, galactosemia, sickle cell disease, cystic fibrosis
what is protein gylcosylation
process by which sugar “trees” (glycans) are creatde, altered and chemically attached to certain proteins or fats
when does glycosylation occur
post translationally
what are congenital disorders of glycosylation characterized by
-prminent forehead
-dyslplastic ears
-thin upper lip
-prominent jaw
-prominent nose and anteverted nostrils
-high arched palate
what are the types of glycosylation
-simple monosaccharide modifications of nuclear transcription factors
- complex branched polysaccharides (GAGs) on cell surface receptors
how does glycosylation affect proteins
impacts protein folding, distribution, stability and activity
what is N linked glycosylation
amide bone formed between N-acetylglucosamine and the asparagine in a protein
where does N linked glycosylation occur
ER
what is O linked glycosylation
carbohydrates bound to a protein backbone through N-acetylgalactosamine and free hydroxyl residues on the protein
where does O linked glycosylation occur
ER and golgi
Describe the phenotype impact of O linked glycosylation
all lead to a similar phenotype
describe the impact of N linked glycosylation on phenotype
mutations do not give the same phenotype
how is CDG tested for
- simple blood test to analyze the glycosylation status of transferrin
- electrospray. ionization-mass spectrometry to detect abnormal transferrin
-enzyme activity assay for some subtypes - molecular genetic testing
what are GAGs
a family of highly sulfated, complex linear polysaccharides
what molecules do GAGs play a role in
-heparin/heparan sulfate
-chondroitin sulfate/dermatan sulfate
- keratan sulfate
-hyaluronan
what do GAGs do
-tensile strength and elasticity
-resists compressive force
what are MPS diseases caused by
lysosomal storage of GAGs that result in skeletal deformities, poor joint mobility, severe growth deficit, coarse facial features, and enlarged organs
what are MPS 1 (Hurler Syndrome) and MPS 2 (Hunter Syndrome) characterized by
gingival hyperplasia, delayed tooth eruption, malocclusion, mandibular dysplasia, radiolucent lesions in the jaws, and condylar defects
what is MPS 3 (Sanfilippo) syndrome characterized by
obliteration of pulp chambers and irregular root canals
what is MPS 4 (Morquio syndrome) characterized by
enamel defects with generalized loss of tooth structure
what is MPS 6 (Marateaux-Lamy syndrome) characterized by
multiple dentigerous systs, macroglossia, fibrous gingival hyperplasia, generalize 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
what are lysosomal storage disorders
MPS 1 and MPS 2 and ML (mucolipidosis)
what are examples of metabolic disorders
MPS1 and MPS2 and ML and Smith Lemli Opitz syndrome
what is smith-Lemli_opitz syndrome (SLOS)
-disorder of cholesterol metabolism caused by a mutation in the DHCR7 gene
-high cholesterol precursors low cholesterol
what does SLOS affect
multiple anomalies (cardiac, urogenital, digit, renal, pulmonary), dysmorphic face, growth deficiency, mental retardation including autism, epilepsy, aggression and self mutilation
