Metabolic Disease & the Maxillofacial Complex

Question 1

What is metabolic disease?

Answer 1

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

Question 2

Thousands of enzymes participate in dozens of _________ metabolic pathways

Answer 2

interdependent

Question 3

Are metabolic disease heritable?

Answer 3

typically yes

Question 4

Do all metabolic diseases present the same?

Answer 4

no, they differ and in some cases appear only when the body is stressed

Question 5

What is typically affected by metabolic disease?

Answer 5

bone/mineralized tissue and cartilage

Question 6

what stages of life are affected by metabolic disease?

Answer 6

all!
infancy–> reflects an impact on embryo/fetus
adolescence–> hormonal influence
adult–> can be due to lifestyle

Question 7

What are some factors that can influence metabolic disease?

Answer 7

genetics, nutrition, gender, age, environment, cultural, occupation, and other diseases/co-morbidities

Question 8

how do genetics influence metabolic disease?

Answer 8

genes encode for the enzymes that regulate the pathways

Question 9

how does nutrition influence metabolic disease?

Answer 9

vitamins form precursors to metabolic pathways

Question 10

What are some of the things that can be screened for in newborn screening?

Answer 10

Phenylketonuria (PKU), hypothyroidism, galactosemia, sickle cell disease, and cystic fibrosis

Question 11

What is a benefit for newborn screening?

Answer 11

allow for early treatment or dietary intervention to prevent/manage/delay symptoms

Question 12

What is protein glycosylation?

Answer 12

sugar trees (glycans) are created, altered, and chemically attached to certain proteins or fats
-one of the major post-translational modification
-impacts protein folding, distribution, stability, and activity

Question 13

How many genes are in the human genome?

Answer 13

20,000-25,000

Question 14

How many tRNAs can be made with modifications?

Answer 14

over 100,000
*due to large variability in pattern of glycosylation

Question 15

What are 5 types of protein glycosylation?

Answer 15

N-glycosylation**
O-glycosylation**
Glypiation
C-glycosylation
Phosphoglycosylation

Question 16

What determines the pattern of glycosylation?

Answer 16

the cell type or tissue type

Question 17

Why does glycosylation change based on the tissue type?

Answer 17

Different genes are active in different tissues

Question 18

N-linked glycosylation

Answer 18

amide bond formed between N-acetylglucosamine and the Asparagine (N)
*typically see attached to two blue boxes

Question 19

Where does N-linked glycosylation occur?

Answer 19

endoplasmic reticulum

Question 20

O-linked glycosylation

Answer 20

carbs bind to protein backbone by N-acetylgalactosamine and the free hydroxy residue on serine, threonine, and tyrosine on the protein

Question 21

Where does O-linked glycosylation occur?

Answer 21

ER and golgi

Question 22

How many congenital disorders of glycosylation (CDG) are there?

Answer 22

around 130

Question 23

What are some of the dysmorphic features of CDGs?

Answer 23

prominent forehead, dysplastic ears, thin upper lip, long philtrum, and prominent jaw

Question 24

How many genes are responsible for O-linked glycosylation?

Answer 24

12 genes

Question 25

Do all mutations in N-glycosylation present the same phenotype?

Answer 25

No, disorders shown will differ based on where the mutation occurs and what sugars are added in what order *group in clusters

Question 26

Do all mutations in O-glycosylation present the same phenotype?

Answer 26

yes- similar phenotypes

Question 27

What is a new tool that has been able to use to try and determine is there metabolic diseases?

Answer 27

AI has been used to scan and compare features of different diseases to see the possibility of having the disease -not a diagnostic tool, but can give good insight

Question 28

What does the PMM2 gene encode for?

Answer 28

enzyme that generates mannose-1-phosphate from mannose-6-phosphate -creates a sugar that can be added

Question 29

What are some possible clinical testing for CDG?

Answer 29

-simple blood test -isoelectric focusing: separate molecules based upon electrical charge -electrospray ionization-mass spectrometry -enzyme activity assay -molecular genetic testing

Question 30

simple blood test for CDGs

Answer 30

analyzes the glycosylation status of transferrin (normally heavily glycosylated)

Question 31

What are glycosaminoglycans? (GAGs)

Answer 31

highly sulfated, complex linear polysaccharides have repeating disaccharide units

Question 32

What are some examples of GAGs?

Answer 32

heparan sulfate, chondroitin sulfate, dermatan sulfate, keratan sulfate, and hyaluronan (hyaluronic acid)

Question 33

how do GAGs differ?

Answer 33

have different repeating disaccharide combinations

Question 34

How much water can GAGs bind to?

Answer 34

1000x their weight

Question 35

Where are GAGs sulfonated?

Answer 35

in the golgi

Question 36

Which GAG is not sulfated?

Answer 36

hyaluronan

Question 37

what is the function of GAGs extracellularly?

Answer 37

form extracellular "gel" which gives the extracellular matrix: -tensile strength and elasticity -resist compressive force

Question 38

Roles of GAGs:

Answer 38

strutural properties are critical for modulating receptor/ligand binding, affecting cell function and tissue morphogenesis -determine how cells respond to growth factors and extracellular stress

Question 39

What are mucopolysaccharidoses?

Answer 39

-group of 7 disorders -deficiency in 1 of 11 enzymes involved with the breakdown of GAGs -causes excessive lysosomal storage of GAGs

Question 40

Prevalence of MPS

Answer 40

1.9-4.5 of 100,000 live births *very rare

Question 41

What do MPSs cause?

Answer 41

over accumulation of GAGs -result in skeletal abnormalities, poor joint mobility, severe growth deficit, coarse facial features, and enlarge organs

Question 42

MPSs have _____ features, but _______ variability

Answer 42

common; inter-individual

Question 43

MPS I and MPS II (Hurlers syndrome)

Answer 43

gingival hyperplasia, delayed tooth eruption, malocclusion, mandicular dysplasia, radiolucent lesion in the jaw, and condylar defects

Question 44

MPS III (sanfilippo syndrome)

Answer 44

obliteration of pulp chambers and irregular root canals

Question 45

MPS IV (Morquio syndrome)

Answer 45

enamel defects with generalized loss of tooth structure

Question 46

MPS VI (Marateaux-Lamy syndrome)

Answer 46

multiple dentigerous cysts, macroglossia, fibrous gingival hyperplasia, generalized bone rarefractions, expanded marrow spaces, cortical wear, impairment of TMJ, impacted teeth, and morphological alterations in nasal cavity and maxillary sinuses

Question 47

Smith-Lemli-Optitz syndrome

Answer 47

disorder of cholesterol metabolism -mutation in DHCR7 gene -one of the final steps in cholesterol formation -mental retardation, autism, epilepsy, agression, self-mutilation -if found early, symptoms can be improved with cholesterol supplementation

Question 48

Functions of cholesterol:

Answer 48

cell membrane, Myelin, bile acids, steroid hormones, and SHH signaling