BC 32 BC Basics of Biochem Disease Flashcards
Enzymopathies in General
- lower the protein or enz activity the more severe the pathology
- almost ALWAYS autosomal recessive
- most are produced in such excess that heterozygotes with 50% activity are still clinically normal
- many still normal with just 10%
Significance of Inheritance of Enzymopathies
Recessive Traits-usually enzymes of Peptide Hormones
- esp enzymes involed in regulation
- manifest only if both copies present
Dominant Traits: usually non enz or structural proteins
-both homo and heterozygotes
Diffusible vs macromolecular
substrate determines pathology
substrate is small molecule ie phenylalanine- easily distributed throughout body by diffusion or transport, site of disease unpredictable
Substrate is a macromolecule: mucopolusaccharide
- trapped in organelle or cell
- pathology contained to tissue of accumulation
-stubstrate can be trapped and derivatives escape, non localized effects
Loss of multiple enzymes paths from enzymopathy…how can this happen
share common subunit,
processed by common mod enzyme
entire organelle can be defective
aldolase B deficiency
normally converts fructose 1 P to glyceraldehyde (eventually Glyceraldehyde 3 P for glycolysis)
- accumulation of F1P (osmotically active compound) leads to liver damage
- decreased cellular Pi (Pi tied to F1P
- –decreased hepatic liver glycogenolysis
- –decreased ATP synthesis
- severe hypoglycemia
- jaundice from liver damage
- hepatic failure from liver damave
- avoid dietary fructose and sucrose
- CATARACTS NOT A FEATURE
- fructose not an aldose sugar (?)
Gal–1-P uridyltransferase deficiency
converts UDP glucose to UDP galactose (cellular pool)
Metabolic block results in accumulation of falactose 1 P, osmotically active resulting in liver damage
-TWO FOLD
accumulation of galactose (upstream substrate in liver and other tissues)
-galactose is converted to galactitol, by aldose reductase (damaging)
- galactosemia (Galactose in Blood)
- galactosuria (in urine)
- liver damage (acc of G1P and Galactitol)
- extrahepatic tissue damage
- CATARACTS due to galactitol accumulation in lens (increase osmo other proteins denatured)
- galactitol nerve damage, sever mental retard
remove ALL dietary galactose (lactose or galactose)
-screened
sig of UDP Gal C4 epimerase
???
Classic Phenylketonuria
mutations in gene encoding hepatic phenylalanine hydroxylase
-converts phenylalanine to tyrosine in liver
autosomal recessive
-accumulation of phenylalanine and phenylpyruvic acid (derivative via alternate reaction and red tyrosine)
Hyperphenylalaniremia: diffusible molecule in all body fluids
-irreversible CNS damage retardation 4 weeks post natal
phenylalanine restricted diet
-tyrosine supplements
MATERNAL PKU
-even if heterozygous
Guthrie Test
drops of baby blood, paper placed in agar, bacteria will grow with excessive phenylalanine
GSD Type 0
Glycogen synthase (GLYCOGENESIS)
-fasting hypoglycemia and muscle cramping (occasional)
- feeding relives symptoms but still post prandial hyperglycemia and lactiacidemia
- –due to shunting excessive pyruvate to LA
GSD type IV
hepatic Branching Enzyme (GLYCOGENESIS)
- Andersons Disease
- accumulation of VERY long branches leads to liver cirrhosis and death by age five
immune respose to cells with abnormal branches
Type VI GSD
hepatic glycogen phophorylase (partial defect) (GlYCOGENOLYSIS)
Sever hepatomegaly (filled with h2o) glycogen accumulation mild hepoglycemia to nothing
Type V GSD
Glycogen Phosphorylase (GLYCOGENOLYSIS) MUSCLE
- McArdel
- exercise induced cramps and intolerance
Type III GSD
Debranching enzyme (GLYCOGENOLYSIS)
- CORI disease
- hepatomegaly: fasting hypoglycemia and myopathy
Type I GSD
Glucose 6 phosphate (glycogenolysis)
Von Gierke
Lethargy, seizures, hepatomegaly
Type II GSD
lysosomal glycogen degradation
-lysosomal alpha glucosidase
not necessary for BG homeo
POMPE disease
-heart attach musle disfunction, weakness…death by 2
