Cholesterol Synthesis Mnemonic

Sources of cholesterol

1. Dietary intake: Most cells derive their cholesterol from LDL or HDL

2. De novo synthesis: Occurs in the liver, where cholesterol is synthesized from acetyl-CoA in cytoplasm.


“Ah Ah Help Me – Plan In Diet Good Food- Stay Low in Cholesterol”

The sequential steps of formation of cholesterol

cholesterol synthesis pathway

Correlate with the mnemonic above:

  1. AcetylCoA (2 C)
    • Citrate shuttle shifts mitochondrial Acetyl-CoA into cytoplasm
  2. AcetoacetylCoA (4 C)
    • Action of 3-Hydroxy-3-MethylGlutaryl (HMG) – CoA synthase (cytoplasm)
  3. HMG CoA (6 C)
    • Action of HMG-CoA reductase (rate-limiting enzyme) in ER –
      • Inhibited by: Statins, Glucagon, Cholesterol
      • Activated by: Insulin
    • 2 NADPH used (from HMP pathway)
  4. Mevalonate (6 C)
    • Pyrophyosphorylation
  5. Pyrophosphomevalonate (6 C)
    • Decarboxylation
  6. Isopentanyl pyrophosphate (5 C)
    • Isomerization
  7. Dimethylallyl pyrophosphate (5 C)
    • Addition of isopentanyl pyrophosphate (5 C)
  8. Geranyl pyrophosphate (10 C)
    • Addition of isopentanyl pyrophosphate (5C)
  9. Farnesyl pyrophosphate (15 C)
    • Action of Squalene synthase (2 X Franesyl pyrophosphate)
    • NADPH required
    • Franesyl PPi is important for:
      • Synthesis of CoQ (Electron Transport Chain)
      • Synthesis of Dolichol PPi for N-linked glycosylation of proteins
      • Prenylation of proteins (post-translational modification)
  10. Squalene (30 C)
    • Action of Squalene epoxidase
    • NADPH required
  11. Lanosterol (30 C)
    • Series of 19 reactions
  12. Cholesterol (27 C)
    • Component of cell membrane
    • Steroid synthesis
    • Vitamin D synthesis
    • Bile acid synthesis

Mechanism of Rhabdomyolysis by Statins

Statins block production of Farnesyl PPi by blocking HMG CoA reductase in the synthesis of lipid pathway. Farnesyl PPi is needed for production of CoQ. Decreased Farnesyl PPi leads to decreased CoQ required in ETC. Decreased CoQ results in Decreased ATP production in muscles results in dysfunctioning of Sodium/K pump leads to cell swelling and rhabdomyolysis.

Smith‐Lemli‐Opitz syndrome (SLOS)

smith lemli opitz syndrome
Source: Marmara Medical Journal
  • Most common and best understood of the inborn errors of cholesterol metabolism
  • Caused by mutations in DHCR7 which encodes the final enzyme in the cholesterol synthetic pathway
  • Cholesterol is necessary for normal embryonic development and has important functions both before and after birth. It is a structural component of cell membranes and the protective substance covering nerve cells (myelin)
  • Clinical features due to cholesterol deficiency and/or accumulation of cholesterol precursors and their metabolites:
    • Autism
    • Malformation of heart, lungs, kidney, gastrointestinal tract, genitalia
    • Hypotonia
    • Syndactyly and Polydactyly
  • Supplementation of cholesterol is a commonly employed potential therapy

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