Biochemistry Diseases Flashcards
Lipodystrophy
Cause: mutant perilipin
Mechanism: no protection of TG from lipolysis by HSL
Symptoms: extreme loss of adiposity
Diabetes Type 1
Cause: No insulin secretion
Mechanism: starvation with extreme hyperglycemia
Symptoms: “turning muscle into urine”, starvation
Niemann Pick A/B
Cause: sphingomyelinase deficiency
Mechanism: accumulation of sphingomyelin, especially in CNS
Symptoms: hepatosplenomegaly, death
Smith-Lemli-Opitz (SLOS)
Cause: deficiency in 7-dehydrocholesterol reductase (last step in synthesis pathway)
Mechanism: accumulation of toxic intermediates, lack of cholesterol
Symptoms: multisystem embryonic abnormalities
Niemann Pick C
Cause: delayed release of cholesterol from lysosomes following LDL intake
Mechanism: accumulation of LDL contents
Symptoms: progressive neural damage, hepatosplenomegaly, death
Sphingolipidosis
Cause: defective sphingolipid degradation
Mechanism: accumulation of sphingolipids (or gangliosides) in lysosomes
Symptoms: Includes Niemann Pick, Tay-Sachs
Tay-Sachs
Cause: defective enzyme for GM2 ganglioside breakdown in lysosomes
Mechanism: accumulation of GM2 ganglioside, neural swelling and damage
Symptoms: neural problems at 1yr then death
Tangier’s disease
Cause: defective ABC transporter A1
Mechanism: no lipidation of ApoA1 –> no reverse cholesterol transport in HDL from periphery
Symptoms: No ApoA1 or HDL, hyperTG in blood, neuropathy
Hypercholesterolemia drugs
Statins: inhibit HMG reductase (rate limiting step in cholesterol synthesis)
Cholystyramin: reduces reabsorption of bile salts via an insoluble +charged resin
Obesity drugs
Orlistat: blocks pancreatic lipase and FA absorption in gut –> fat in feces
Cholelithiasis
Cause: bile salt deficiency
Mechanism: secretion of more cholesterol than can be solubilized via bile salts
Symptoms: Gallstones
Cystic fibrosis
Cause: pancreatic insufficiency that affects pancreatic lipase
Mechanism: digestive ducts blocked
Symptoms: mucus problems as well due to malfunctioning Na/Cl transporter, poor fat absorption, fat in feces
Type I hyperlipoproteinemia (apoCII deficiency) aka familial lipoprotein lipase deficiency
Cause: lack of lipoprotein lipase or apoCII on chylomicron
Mechanism: no chylomicron breakdown
Symptoms: super hyperTGemia
Type II hyperlipidemia (familial hypercholesterolemia)
Cause: defective LDL receptors
Mechanism: no clearance of LDL from blood, foam cell formation
Symptoms: premature athleroschlerosis
Abetalipoproteinemia
Cause: no microsomal transfer protein (MTTP)
Mechanism: Can’t load ApoB48 (chylomicron) or ApoB100 (VLDL)
Symptoms: No chylomicrons or VLDL, TAGs accumulate in liver and intestine
Fatty liver (hepatic steatosis)
Cause: Imbalance between TAG synthesis and secretion of VLDL
Mechanism: obesity, uncontrolled DM, alcoholism
Symptoms: liver dysfunction
Maple Syrup Urine Disease
Cause: cannot metabolize branched chain amino acids
Mechanism: accumulation of keto-acid byproducts
Symptoms: self-explanatory
Phenylketonuria
Cause: defective phenylalanine hydroxylase (PAH)
Mechanism: accumulation of phenylpyruvate
Symptoms: intellectual disability, seizures
Gout
Cause: overproductive- xanthine oxidase
Mechanism: uric acid builds up in joints
Symptoms: a world of pain
G6PDH deficiency
Cause: missing G6PDH, cannot form NADPH via pentose phosphate pathway (first step)
Mechanism: can’t reduce glutathione, which mops up oxidative damage
Symptoms: hemolytic anemia with certain drugs, infections, etc
Lesch-Nyhan Syndrome
Cause: missing purine salvage pathway via HGPRT
Mechanism: hypoxanthine builds up
Symptoms: neurological difficulties, self-harm
Adenosine Deaminase Deficiency
Cause: missing adenosine deaminase, recycles adenosine back to iosine
Mechanism: adenosine inhibits de novo synthesis, impairs DNA synth
Symptoms: significant immunodeficiency
