Metabolic Disease Flashcards
what is a metabolic disease?
any disruption of the ability of the cell to perform critical biochemical reactions involved in the processes of converting food to energy on a cellular level (ex. metabolism)
metabolic disease can involve
the processing, transport or absorption of proteins (amino acids), carbohydrates (sugars and stretches), or lipids (fatty acids)
thousands of enzymes participate is dozens of
interdependent metabolic pahtways
is metabolic disease heritable?
typically yes
level of robustness with “feedback” mechanisms to help regulate
pathway activities
variable in presentation, in many cases only appearing when the body is
stressed
many affect (3)
bone, mineralized tissue, cartilage
impact on maxillofacial complex can be variable and affect all stages of life
infant, reflecting an impact on the embryo/fetus
adolescence
adult
influencing factors include (8)
genetics nutrition gender age environment cultural occupation other diseases/co-morbidities
in severe cases, — — is done
prenatal screening
newborn metabolic screening (non standardized) in all states allows for
early treatment or dietary intervention to prevent/manage/delay symptoms
examples of newborn metabolic screening (non standardized) in all states (5)
PKU, hypothyroidism, galactosemia, sickle cell disease, CF
glycoslyation
process by which sugar trees (glycans) are created, altered and chemically attached to certain proteins or fats (lipids)
one of the major post translational modifications
glycoslylation
CDG
congenital disorders of glycolsylation
~— subtypes of CDG
130
CDG is characterized by variably dysmorphic features such as
Prominent forehead, dysplastic ears and large ear lobules, thin upper lip, long philtrum, prominent jaw (develops with age as mandible can start as retrognathic), narrow/short palpebral fissures, prominent nose and anteverted nares, high-arched palate, long and slender fingers and toes, peau d’orange (skin of an orange), strabismus, inverted nipples, abnormal fat distribution, cardiac defects, liver and bile duct abnormalities, urogenital malformations
simple monosaccharide modifications of
nuclear transcription factors
complex branched polysaccharides (GAGs) on
cell surface receptors
what does protein glycosylation impact?
protein folding, distribution, stability and activity
the pattern of glycoslation is often
cell type specific
due to differential expression of the genes encoding the
respective enzymes
large variation in pattern because of the difference in
sugar moieties added
N linked glycosylation
efers 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).▸O-linked
O linked glycosylation
carbohydrates bound to a protein backbone through hydroxyl residues (eg. on Ser, Thr, Tyr). Occurs mostly in ER & Golgi.
mutations in any of the 12 genes responsible for O linked glycoslation all lead to a similar
phenotype