Block 2 Dieases Flashcards
Arsenite poisoning
binds lipoic acid
interferes with E2 of pyruvate dehyrogenase and to alpha-ketoglutarate DH, inhibits gluconeogenesis
build-up of pyruvate and then lactate
von Gierke disease enzyme
glucose 6-phosphatase
von Gierke features
liver and kidney glycogen accumulation, doll-like facial features, thin extremities, short stature, protuberant abdomen, PCOS in untreated females
lactic acidosis, hyperlipidemia, hypoglycemia
Pompe disease enzyme
lysosomal hydrolase (debranching enzyme, 4:4 transferase and 1:6 glucosidase)
Pompe disease features
lysosomal glycogen accumulation
juvenile-onset hypoglycemia, muscle hypotonia, heart failure, cardiomegaly, floppy baby syndrome
adult-onset: muscular dystrophy
McArdle disease enzyme
muscle glycogen phosphorylase
NORMAL GLYCOGEN STRUCTURE
McArdle disease features
poor exercise tolerance, high m. glycogen, blood lactate low after exercise, burgundy urine
Hers disease enzyme
liver glycogen phosphorylase
Hers disease features
hepatomegaly, liver glycogen accumulation, mild hypoglycemia, good prognosis
Forbe/Cori disease enzyme
liver and muscle debranching enzyme
=limit dextrinosis
ABNORMAL GLYCOGEN STRUCTURE
GSD (Glycogen Storage Disease) Type 0 enzyme
glycogen synthase
GSD (Glycogen Storage Disease) Type 0 features
hyperketonemia, hypoglycemia, early death
G6PD deficiency features
neonatal jaundice, acute hemolytic anemia, Heinz bodies (cross-linked, denatured proteins)
G6PD deficiency
X-linked
inability to carry out PPP prevents formation of NADPH, cannot regenerate GSH (glutathione, req. NADPH) to cope with ROS
Fructosuria enzyme
fructokinase
Fructosuria features
autosomal recessive
fructose accumulation in urine, benign
HFI, Hereditary Fructose Intolerance enzyme
aldolase B
HFI features
trapping of F1P, no phosphate produced
severe hypoglycemia, vomiting, jaundice, hepatomegaly, hemorrhage, hyperuricemia, lactic acidemia, hemorrhage
cannot metabolize fructose, sucrose, or sorbitol
Type I galactosemia enzyme
GALT, galactose 1-P uridyltransferase
Type I galactosemia features
classic type
response to lactose/galactose: vomiting, diarrhea, jaundice, liver damage, severe mental retardation, cataracts, ovarian failure
Type II galactosemia enzyme
GALK, galactokinase
Type II galactosemia features
lactose/galactose response: cataracts, galactosuria, no long-term complications
Type III galactosemia enzyme
GALE, UDP-hexose 4-epimerase
Type III galactosemia features
relatively benign, usually only affects red and white blood cells unless rare form ~Type I
Hunter syndrome GAGs build-up
dermatan sulfate and heparan sulfate
Hunter syndrome features
X-LINKED !
NO corneal clouding, physical deformity, mental retardation
Hurler syndrome GAGs build-up
dermatan sulfate and heparan sulfate
Hurler syndrome features
autosomal recessive
CORNEAL CLOUDING, dwarfing, hearing loss, upper airway obstruction, coronary artery deposition–>death
San Filippo syndrome GAGs build-up
heparan sulfate
San Filippo syndrome features
autosomal recessive
4 types
severe nervous system disorders, mental retardation
Sly syndrome GAGs build-up
dermatan sulfate and heparan sulfate
Sly syndrome features
autosomal recessive
CORNEAL CLOUDING, hepatosplenomegaly, skeletal deformity, short stature, mental deficiency
I-cell disease pathology
INCLUSION bodies of improperly processed N-linked glycoproteins meant as lysosomal enzymes–>exported out of cell
inability to phosphorylate mannose and address glycoprotein to lysosome
deficiency of hydrolytic enzymes in lysosomes
I-cell disease features
skeletal abnormalities, joint restriction, coarse facial features, severe psychomotor problems, death by age 10
Steatorrhea cause
lipid malabsorption
Cystic fibrosis defect
CFTR gene mutation
folding defect and degradation of protein ERAD leads to non0functional chloride channels on all epithelial cells
Cystic fibrosis features
pancreatic insufficiency, thickened pancreatic secretions prevent lipases from reaching intestine, rely on gastric lipase
Orlistat function
anti-obesity drug
competitive inhibitor for pancreatic and gastric lipases
Chylomicronemia
build-up of chylomicrons, result from lipid malabsorption
Type I hyperlipoproteinemia (familia lipoprotein lipase deficiency) deficiency
APOC2 deficiency leads to non-functional lipoprotein lipase (cofactor)
Type III hyperlipoproteinemia (familial dysbetalipoproteinemia) deficiency
APOE deficiency, inability to synthesize chylomicrons (deficient core protein)
Hyperlipoproteinemia features
pancreatitis, neuralgias, xanthomas, chylomicronemia
Ezetimibe function
lowers cholesterol
binds to NPC1L, carrier protein for cholesterol transport
Mucopolysaccharidoses
Hunter, Hurler, San Filippo, Sly syndromes
Carnitine deficiency features
muscle weakness, cardiomyopathy, acute encephalopathy, hypoglycemia, chronic infections
Congenital carnitine palmitoyl transferase (CPT-I or CPT-II) deficiencies pathology
prevent carnitine shuttle in fatty acid degradation
Peroxisome Biogenesis Disorders (PBDs) pathology
interfere with peroxisomal beta-oxidation for very long fatty acid chains
Zellweger syndrome pathology
Peroxisome Biogenesis Disorder
autosomal recessive
adrenoleukodystrophy
Peroxisome Biogenesis Disorder
X-linked (Lorenzo’s Oil)
Zellweger syndrome features
impaired neuronal migration, brain development
Adrenoleukodystrophy features
mental impairment, motor problems
Refsum’s disease deficiency
alpha-hydroxylase
prevents alpha-oxidation of fatty acids
Refsum’s disease features
retinitis pigmentosum, deafness, cerebellar ataxia
Hyaline membrane disease pathology
low production of DPPC, dipalmitoyl phosphatidyl choline, lung surfactant from PC synthesis (salvage pathway or de novo)
Hyaline membrane disease features
respiratory distress syndrome
common in premature infants
Paroxysmal nocturnal hemoglobinuria pathology
deficiency of GPI, glycosyl phosphatidyl inositol, anchoring protein from PI phospholipid synthesis
Paroxysmal nocturnal hemoglobinuria features
hemolytic disease, loss of protein anchoring–> RBC hemolysis
Niemann-Pick disease enzyme
sphingomyelinase, loss-of-function mutation
Niemann-Pick disease features
severe mental retardation, hepatosplenomgaly, death in early adulthood, higher incidence in Ashkenazi Jews
Niemann-Pick disease lipid accumulation
sphingomyelin
Niemann-Pick primary organs
brain, liver, spleen
Tay-Sachs disease enzyme
beta-hexosaminidase A
Tay-Sachs lipid accumulation
ganglioside GM2
Tay-Sachs primary organs
brain
Sphingolipidoses
Tay-Sachs, Gaucher, Fabry (X-linked), Niemann-Pick, Farber
Gaucher disease enzyme
glucocerebrosidase
Gaucher disease lipid accumulation
glucocerebroside
Gaucher disease primary organs
brain, liver, spleen
Fabry disease enzyme
alpha-galactosidase
Fabry disease lipid accumulation
ceramide trihexoside
Fabry disease inheritance
X-linked
Farber disease enzyme
ceramidase
Farber disease lipid accumulation
ceramide
Farber disease primary organs
joints, liver, spleen
Fabry disease primary organs
kidney
MCAD (medium chain-length acyl CoA DH) deficiency pathology
decreased fatty acid beta-oxidation leads to lipid build-up
MCAD features
associated with SIDS and Reye syndrome
severe hypoketotic hypoglycemia
autosomal recessive loss-of-function point mutation
Pyruvate dehydrogenase complex deficiency features
cerebral lactic acidosis, encephalopathy
Thiamine deficiency (TPP, vit B1) features
CNS problems, no ATP produced
Forbe/Cori disease features
fasting hypoglycemia, hepatomegaly in infancy, muscle weakness
