Complex Lipids & Cholesterol Biochemistry Flashcards Preview

DEMS: Unit II > Complex Lipids & Cholesterol Biochemistry > Flashcards

Flashcards in Complex Lipids & Cholesterol Biochemistry Deck (16):
1

Sources of cholesterol

 

  • Diet: consume ~300-600 mg/day 
    • Half is absorbed
  • De novo synthesis: ~1gm/day
    • Mostly in liver (highly regulated process)

2

General steps of de novo cholesterol synthesis

 In hepatocyte cytoplasm:

Acetyl CoA (thiolase & HMG CoA synthase) --> HMG CoA (HMG CoA reductase*) + NADPH --> NADPH --> mevalonate --> lots of complicated steps resulting in key intermediates geranyl pyrophosphate and farnesyl pyrophosphate --> cholesterol

*key regulated step, rate limiting

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3

Key regulated step in cholesterol synthesis

HMG CoA (HMG CoA reductase*) + NADPH --> mevalonate

Primary means for controlling intracellular cholesterol levels

4

4 levels of HMG CoA reductase regulation

  • Transcriptional regulation
  • Translational regulation
  • Regulation of degradation
  • Regulation of phosphorylation

5

Key features of glycerophospholipids, sphingomyelin, glycosphingolipids (general)

  • All lipids begin with glycerol or ceramide (sphingosine) backbone 
  • Polar head group: 
    • Phosphate linked to alcohol: glycerophospholipid
    • Phosphate linked to choline: sphingomyelin
    • Sugar moiety: glycosphingolipids

**Sphingolipids have no glycerol backbone - instead sphingosine with nitrogen in it

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6

Synthesis of different glycerophospholipids

  • Backbone comes from phosphatidic acid (precursor in triglyceride biosynthesis)
  • Head group added:
    • Phosphatidylserine (PS)
    • Phosphatidylethanolamine (PE)
      • Head group formed de novo or from diet, activated by CDP then attached to backbone
    • Phosphatidylcholine (PC)
      • Head group formed de novo or from diet, activated by CDP then attached to backbone

  • Another synthesis pathway: "base exchange"
    • Head groups exchanged onto previously synthesized phospholipids

7

Important functions of sphingomyelin

  • Major structural lipid in nerve tissue

8

Important functions of phosphatidylinositol

  • Important in signal transduction
  • Reservoir for arachidonic acid
  • Important in membrane protein anchoring

9

Important functions of phosphatidylcholine

  • Lung surfactant
  • Reservoir of choline
  • Present in bile
  • Most abundant phospholipid in body

10

Synthesis of arachidonic acid

Made from dietary linoleic acid

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11

Synthesis of prostaglandins

Synthesized from arachidonic acid by COX

12

Fates of cholesterol

  • Steroid hormones
  • Bile acids
    • Secrete 300-600mg of cholesterol in bile salts/day
  • Component of membranes
  • Vitamin D

13

Transcriptional regulation of HMG-CoA reductase

  • Cholesterol present in excess --> HMG CoA reductase gene transcribed 20x less
  • Insulin/glucagon regulate via transcription
    • Insulin increases expression of enzyme (high in fed state when NADPH is high)
    • Glucagon decreases expression

14

Translational regulation of HMG-CoA reductase

  • Cholesterol present in excess --> translation rate of coding mRNA 5x less than in absence of cholesterol
  • mRNA half-life decreases with excess cholesterol

15

Regulation of degradation of HMG-CoA reductase

  • In excess cholesterol --> half-life of HMG-CoA reductase decreases from 11 hours to 2 hours

16

Regulation of phosphorylation of HMG-CoA reductase

  • AMP kinase phosphorylates HMG-CoA reductase --> inactivates
  • Protein phosphatase removes phosphate --> activates