Biochemistry Diseases

Question 1

Lipodystrophy

Answer 1

Cause: mutant perilipin
Mechanism: no protection of TG from lipolysis by HSL
Symptoms: extreme loss of adiposity

Question 2

Diabetes Type 1

Answer 2

Cause: No insulin secretion
Mechanism: starvation with extreme hyperglycemia
Symptoms: “turning muscle into urine”, starvation

Question 3

Niemann Pick A/B

Answer 3

Cause: sphingomyelinase deficiency
Mechanism: accumulation of sphingomyelin, especially in CNS
Symptoms: hepatosplenomegaly, death

Question 4

Smith-Lemli-Opitz (SLOS)

Answer 4

Cause: deficiency in 7-dehydrocholesterol reductase (last step in synthesis pathway)
Mechanism: accumulation of toxic intermediates, lack of cholesterol
Symptoms: multisystem embryonic abnormalities

Question 5

Niemann Pick C

Answer 5

Cause: delayed release of cholesterol from lysosomes following LDL intake
Mechanism: accumulation of LDL contents
Symptoms: progressive neural damage, hepatosplenomegaly, death

Question 6

Sphingolipidosis

Answer 6

Cause: defective sphingolipid degradation
Mechanism: accumulation of sphingolipids (or gangliosides) in lysosomes
Symptoms: Includes Niemann Pick, Tay-Sachs

Question 7

Tay-Sachs

Answer 7

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

Question 8

Tangier’s disease

Answer 8

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

Question 9

Hypercholesterolemia drugs

Answer 9

Statins: inhibit HMG reductase (rate limiting step in cholesterol synthesis)
Cholystyramin: reduces reabsorption of bile salts via an insoluble +charged resin

Question 10

Obesity drugs

Answer 10

Orlistat: blocks pancreatic lipase and FA absorption in gut –> fat in feces

Question 11

Cholelithiasis

Answer 11

Cause: bile salt deficiency
Mechanism: secretion of more cholesterol than can be solubilized via bile salts
Symptoms: Gallstones

Question 12

Cystic fibrosis

Answer 12

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

Question 13

Type I hyperlipoproteinemia (apoCII deficiency) aka familial lipoprotein lipase deficiency

Answer 13

Cause: lack of lipoprotein lipase or apoCII on chylomicron
Mechanism: no chylomicron breakdown
Symptoms: super hyperTGemia

Question 14

Type II hyperlipidemia (familial hypercholesterolemia)

Answer 14

Cause: defective LDL receptors
Mechanism: no clearance of LDL from blood, foam cell formation
Symptoms: premature athleroschlerosis

Question 15

Abetalipoproteinemia

Answer 15

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

Question 16

Fatty liver (hepatic steatosis)

Answer 16

Cause: Imbalance between TAG synthesis and secretion of VLDL
Mechanism: obesity, uncontrolled DM, alcoholism
Symptoms: liver dysfunction

Question 17

Maple Syrup Urine Disease

Answer 17

Cause: cannot metabolize branched chain amino acids
Mechanism: accumulation of keto-acid byproducts
Symptoms: self-explanatory

Question 18

Phenylketonuria

Answer 18

Cause: defective phenylalanine hydroxylase (PAH)
Mechanism: accumulation of phenylpyruvate
Symptoms: intellectual disability, seizures

Question 19

Gout

Answer 19

Cause: overproductive- xanthine oxidase
Mechanism: uric acid builds up in joints
Symptoms: a world of pain

Question 20

G6PDH deficiency

Answer 20

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

Question 21

Lesch-Nyhan Syndrome

Answer 21

Cause: missing purine salvage pathway via HGPRT
Mechanism: hypoxanthine builds up
Symptoms: neurological difficulties, self-harm

Question 22

Adenosine Deaminase Deficiency

Answer 22

Cause: missing adenosine deaminase, recycles adenosine back to iosine
Mechanism: adenosine inhibits de novo synthesis, impairs DNA synth
Symptoms: significant immunodeficiency