,USMLE Step 1 Biochemistry + Molecular
Biology | Lipid Metabolism, Storage Diseases
& Nucleotide Pathways | Verified High-Yield
Notes 2025.
HMG CoA Reductace Inhibitors
LDL⬇⬇⬇ HDL ⬆ TG ⬇
-statin
Lovastatin, pravastatin, etc
Competitive Inhibitors of HMG-CoA Reductace by appearing like HMG-CoA
Mechanism:
Inhibition of HMG CoA Reductace which results in the decrease of cholesterol intracellularly.
Decrease of intracellularly results in the ⬆ of LDL receptors (which increases the uptake of LDL from
circulation) and ⬇ of LDL secretion.
Adverse Effects: (rare)
Mostly due to the decrease of byproduct Farnesyl PPi; it is important for the synthesis of CoQ in the
Electron Transport Chain (mostly located in muscle and liver)
Liver - liver function failure
Muscle* - myopathy and rhabdomyolysis (disintegration or dissolution of muscle), most cases involve
patients with renal insufficiency or taking drugs like cyclosporine, erythromycin, niacin.
Niacin
Vit. B3
Most effective drug for raising HDL
LDL⬇⬇ HDL⬆⬆⬆ TG⬇
Mechanism:
Inhibits lipolysis in adipose tissue, which lowers the circulating fatty acids that liver uses to produce TG
and cholesterol (VLDL and LDL)
Adverse Effects:
Red flushed face, pruritus, can be relieved by aspirin
Resins
,LDL⬇⬇ HDL⬆ TG⬆
Cholestyramine, colestipol, colesevelam
Mechanism:
- Drug inhibits the uptake of bile acids from small intestines which promotes the liver to convert more
cholesterol into bile acid too maintain the balance and hence lowering cholesterol
- 7a-hydroxylase activated due to decrease in circulating bile acid
(similar effects of a HIGH-FIBER DIET, cellulose will bind to bile acid and decrease circulating BA and
activate 7a-hydroxylase)
Adverse Effects:
Patients hate it because it tastes bad.
GI: most common; constipation, nausea, etc.
Liver: Pruritus in liver failure patients and diarrhea
Absorption: ⬇ uptake of fat soluble vitamins
CONTRAINDICATED in patients with gallstones (due to increase of production of bile acid)
Ezetimibe
Cholesterol absorption inhibitor
LDL⬇⬇ HDL- TG-
Mechanism:
Inhibits dietary and biliary cholesterol absorption in the small intestines to the liver; decreases
cholesterol stores and increases the uptake of cholesterol from circulation.
Adverse Effects: rare but should not use in patients with severe liver insufficiency.
Fibrates
LDL⬇ HDL⬆ TG⬇⬇⬇
Fenofibrate, gemfibrozil
Mechanism:
Upregulates lipoprotein lipase LPL which increases TG clearance.
Adverse effects:
GI: mild disturbances
Lithiasis: formation of gallstones due to increase in biliary cholesterol secretion.
Muscle: myositis (tender muscle)
Tay Sachs Disease
, Sphingolipidoses (lysosomal storage disease)
Inheritance: AR
Deficient: hexsoaminidase A
Accumulated: GM2-ganglioside
Findings:
1. Cherry red spot on macula
2. Lysosomal with onion skin
3. Progressive neurodegeneration
4. Ashkenazi Jews
NO HEPATOSPLENOMEGALY vs. Niemann-Picke's Disease
KJ: hey seXy don't look at my GM2
Fabry's Disease
'Fairy'
Sphingolipidoses (lysosomal storage disease)
Inheritance: XR
Deficient: α-galactosidase A
Accumulated: Ceramide trihexoside
Findings:
1. Peripheral neuropathy of hands/feet
2. Angiokeratoma
3. Cardiovascular/renal disease
4. No neurodegeneration
KJ: Fairy has a cups and don't have sex (XR), so when a man touches her she has heart
(Cardiovascular/renal) problems and can't feel (neuropathy of hands/feet)
Gaucher's Disease
Most common sphingolipidoses (lysosomal disease)
AR
Deficient: β-glucocerebrosidase
Accumulated: glucocerebroside
Findings:
1. Hepatosplenomegaly
2. Aseptic necrosis of femur
3. Bone crises
Biology | Lipid Metabolism, Storage Diseases
& Nucleotide Pathways | Verified High-Yield
Notes 2025.
HMG CoA Reductace Inhibitors
LDL⬇⬇⬇ HDL ⬆ TG ⬇
-statin
Lovastatin, pravastatin, etc
Competitive Inhibitors of HMG-CoA Reductace by appearing like HMG-CoA
Mechanism:
Inhibition of HMG CoA Reductace which results in the decrease of cholesterol intracellularly.
Decrease of intracellularly results in the ⬆ of LDL receptors (which increases the uptake of LDL from
circulation) and ⬇ of LDL secretion.
Adverse Effects: (rare)
Mostly due to the decrease of byproduct Farnesyl PPi; it is important for the synthesis of CoQ in the
Electron Transport Chain (mostly located in muscle and liver)
Liver - liver function failure
Muscle* - myopathy and rhabdomyolysis (disintegration or dissolution of muscle), most cases involve
patients with renal insufficiency or taking drugs like cyclosporine, erythromycin, niacin.
Niacin
Vit. B3
Most effective drug for raising HDL
LDL⬇⬇ HDL⬆⬆⬆ TG⬇
Mechanism:
Inhibits lipolysis in adipose tissue, which lowers the circulating fatty acids that liver uses to produce TG
and cholesterol (VLDL and LDL)
Adverse Effects:
Red flushed face, pruritus, can be relieved by aspirin
Resins
,LDL⬇⬇ HDL⬆ TG⬆
Cholestyramine, colestipol, colesevelam
Mechanism:
- Drug inhibits the uptake of bile acids from small intestines which promotes the liver to convert more
cholesterol into bile acid too maintain the balance and hence lowering cholesterol
- 7a-hydroxylase activated due to decrease in circulating bile acid
(similar effects of a HIGH-FIBER DIET, cellulose will bind to bile acid and decrease circulating BA and
activate 7a-hydroxylase)
Adverse Effects:
Patients hate it because it tastes bad.
GI: most common; constipation, nausea, etc.
Liver: Pruritus in liver failure patients and diarrhea
Absorption: ⬇ uptake of fat soluble vitamins
CONTRAINDICATED in patients with gallstones (due to increase of production of bile acid)
Ezetimibe
Cholesterol absorption inhibitor
LDL⬇⬇ HDL- TG-
Mechanism:
Inhibits dietary and biliary cholesterol absorption in the small intestines to the liver; decreases
cholesterol stores and increases the uptake of cholesterol from circulation.
Adverse Effects: rare but should not use in patients with severe liver insufficiency.
Fibrates
LDL⬇ HDL⬆ TG⬇⬇⬇
Fenofibrate, gemfibrozil
Mechanism:
Upregulates lipoprotein lipase LPL which increases TG clearance.
Adverse effects:
GI: mild disturbances
Lithiasis: formation of gallstones due to increase in biliary cholesterol secretion.
Muscle: myositis (tender muscle)
Tay Sachs Disease
, Sphingolipidoses (lysosomal storage disease)
Inheritance: AR
Deficient: hexsoaminidase A
Accumulated: GM2-ganglioside
Findings:
1. Cherry red spot on macula
2. Lysosomal with onion skin
3. Progressive neurodegeneration
4. Ashkenazi Jews
NO HEPATOSPLENOMEGALY vs. Niemann-Picke's Disease
KJ: hey seXy don't look at my GM2
Fabry's Disease
'Fairy'
Sphingolipidoses (lysosomal storage disease)
Inheritance: XR
Deficient: α-galactosidase A
Accumulated: Ceramide trihexoside
Findings:
1. Peripheral neuropathy of hands/feet
2. Angiokeratoma
3. Cardiovascular/renal disease
4. No neurodegeneration
KJ: Fairy has a cups and don't have sex (XR), so when a man touches her she has heart
(Cardiovascular/renal) problems and can't feel (neuropathy of hands/feet)
Gaucher's Disease
Most common sphingolipidoses (lysosomal disease)
AR
Deficient: β-glucocerebrosidase
Accumulated: glucocerebroside
Findings:
1. Hepatosplenomegaly
2. Aseptic necrosis of femur
3. Bone crises
