Your SlideShare is downloading. ×
CHOLESTEROL METABOLISM muhammad mustansar FJMC LAHORE
CHOLESTEROL METABOLISM muhammad mustansar FJMC LAHORE
CHOLESTEROL METABOLISM muhammad mustansar FJMC LAHORE
CHOLESTEROL METABOLISM muhammad mustansar FJMC LAHORE
CHOLESTEROL METABOLISM muhammad mustansar FJMC LAHORE
CHOLESTEROL METABOLISM muhammad mustansar FJMC LAHORE
CHOLESTEROL METABOLISM muhammad mustansar FJMC LAHORE
CHOLESTEROL METABOLISM muhammad mustansar FJMC LAHORE
CHOLESTEROL METABOLISM muhammad mustansar FJMC LAHORE
CHOLESTEROL METABOLISM muhammad mustansar FJMC LAHORE
CHOLESTEROL METABOLISM muhammad mustansar FJMC LAHORE
CHOLESTEROL METABOLISM muhammad mustansar FJMC LAHORE
CHOLESTEROL METABOLISM muhammad mustansar FJMC LAHORE
CHOLESTEROL METABOLISM muhammad mustansar FJMC LAHORE
CHOLESTEROL METABOLISM muhammad mustansar FJMC LAHORE
CHOLESTEROL METABOLISM muhammad mustansar FJMC LAHORE
CHOLESTEROL METABOLISM muhammad mustansar FJMC LAHORE
CHOLESTEROL METABOLISM muhammad mustansar FJMC LAHORE
CHOLESTEROL METABOLISM muhammad mustansar FJMC LAHORE
CHOLESTEROL METABOLISM muhammad mustansar FJMC LAHORE
CHOLESTEROL METABOLISM muhammad mustansar FJMC LAHORE
CHOLESTEROL METABOLISM muhammad mustansar FJMC LAHORE
CHOLESTEROL METABOLISM muhammad mustansar FJMC LAHORE
CHOLESTEROL METABOLISM muhammad mustansar FJMC LAHORE
CHOLESTEROL METABOLISM muhammad mustansar FJMC LAHORE
CHOLESTEROL METABOLISM muhammad mustansar FJMC LAHORE
CHOLESTEROL METABOLISM muhammad mustansar FJMC LAHORE
Upcoming SlideShare
Loading in...5
×

Thanks for flagging this SlideShare!

Oops! An error has occurred.

×
Saving this for later? Get the SlideShare app to save on your phone or tablet. Read anywhere, anytime – even offline.
Text the download link to your phone
Standard text messaging rates apply

CHOLESTEROL METABOLISM muhammad mustansar FJMC LAHORE

1,683

Published on

CHOLESTEROL METABOLISM

CHOLESTEROL METABOLISM

Published in: Education
0 Comments
5 Likes
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total Views
1,683
On Slideshare
0
From Embeds
0
Number of Embeds
2
Actions
Shares
0
Downloads
57
Comments
0
Likes
5
Embeds 0
No embeds

Report content
Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
No notes for slide

Transcript

  • 1. DR MUHAMMAD MUSTANSAR
  • 2.  Membrane component Precurser to ◦ Bile acids ◦ Vitamin D ◦ Steroid hormones
  • 3.  Dietary cholesterol ◦ From chylomicron remnants Cholesterol from extra-hepatic tissues ◦ Reverse cholesterol transport via HDL  Chylomicron remnants  IDL De novo synthesis
  • 4.  VLDL -> LDL ◦ Transport to extra-hepatic tissues Direct excretion into bile ◦ Gallstones commonly are precipitates of cholesterol  Occurs when bile becomes supersaturated with cholesterol  Obesity, biliary stasis, infections Bile acid synthesis and excretion into bile
  • 5.  Primary site: liver (~1g/d) ◦ Secondary sites: adrenal cortex, ovaries, testes Overall equation:
  • 6. O OH O − O C CH2 C CH2 C SCoA CH3 hydroxymethylglutaryl-CoAHydroxymethylglutaryl-coenzyme A (HMG-CoA)is the precursor for cholesterol synthesis.HMG-CoA is also an intermediate on the pathway forsynthesis of ketone bodies from acetyl-CoA.The enzymes for ketone body production are located inthe mitochondrial matrix.HMG-CoA destined for cholesterol synthesis is made byequivalent, but different, enzymes in the cytosol.
  • 7. O O H3C C CH2 C SCoA H2 O + O acetoacetyl-CoA H3 C C SCoA acetyl-CoA HMG-CoA HSCoA Synthase O OH O − O C CH2 C CH2 C SCoA CH3 hydroxymethylglutaryl-CoA HMG-CoA is formed by condensation of acetyl-CoA & acetoacetyl-CoA, catalyzed by HMG-CoA Synthase. HMG-CoA Reductase catalyzes production of mevalonate from HMG-CoA.
  • 8.  Formation of HMG CoA (cyto) ◦ Analogous to KB synthesis (mito) Conversion of HMG CoA to activated isoprenoids
  • 9.  Condensation of isoprenoids to squalene ◦ Six isoprenoids condense to form 30-C molecue
  • 10.  Conversion of Squalene to Cholesterol
  • 11.  All carbons from acetyl-CoA Requires NADPH, ATP, & O 2 Stages ◦ One: forms HMG CoA ◦ Two: forms activated 5 carbon intermediates (isoprenoids) ◦ Three: six isoprenoids form squalene ◦ Four: squalene + O2 form cholesterol
  • 12.  Cellular cholesterol content exerts transcriptional control ◦ HMG-CoA reductase  Half life = 2 hours ◦ LDL-receptor synthesis Nutrigenomics: ◦ interactions between environment and individual genes and how these interactions affect clinical outcomes
  • 13.  Covalent Modification of HMG-CoA Reductase ◦ Insulin induces protein phosphatase ◦ Activates HMG-CoA reductase Feeding promotes cholesterol synthesis ◦ Activates reg. enzyme ◦ Provides substrate: acetyl CoA ◦ Provides NADPH
  • 14.  Covalent Modification of HMG-CoA Reductase ◦ Glucagon stimulates adenyl cyclase producing cAMP ◦ cAMP activates protein kinase A ◦ Inactivates HMG-CoA reductase Fasting inhibits cholesterol synthesis
  • 15.  Major excretory form of cholesterol ◦ Steroid ring is not degraded in humans ◦ Occurs in liver Bile acid/salts involved in dietary lipid digestion as emulsifiers
  • 16.  Primary bile acids ◦ Good emulsifying agents  All OH groups on same side  pKa = 6 (partially ionized) Conjugated bile salts ◦ Amide bonds with glycine or taurine ◦ Very good emulsifier  pKa lower than bile acids
  • 17.  Hydroxylation ◦ Cytochrome P-450/mixed function oxidase system Side chain cleavage Conjugation Secondary bile acids ◦ Intestinal bacterial modification  Deconjugation  Dehydroxylation  Deoxycholic acid  Lithocholic acid
  • 18.  Enterohepatic circulation ◦ 98% recycling of bile acids Cholestyramine Treatment ◦ Resin binds bile acids ◦ Prevents recycling ◦ Increased uptake of LDL-C for bile acid synthesis
  • 19. Plant stanolsNo double bond on B ringPlant sterolsDifferent side chains
  • 20. Structures ofCommon statindrugs
  • 21.  8 yo girl ◦ Admitted for heart/liver transplant History ◦ CHD in family ◦ 2 yo xanthomas appear on legs ◦ 4 yo xanthomas appear on elbows ◦ 7 yo admitted w/ MI symptoms  [TC] = 1240 mg/dl  [TG] = 350 mg/dl  [TC]father = 355 mg/dl  [TC]mother = 310 mg/dl ◦ 2 wks after MI had coronary bypass surgery ◦ Past year severe angina & second bypass ◦ Despite low-fat diet, cholestyramine, & lovastatin, [TC] = 1000 mg/dl
  • 22.  Raised, waxy appearing, often yellow skin lesions (shown here on knee) ◦ Associated with hyperlipidemia Tendon xanthomas common on Achilles and hand extensor tendons
  • 23. Xanthomas of the eyelidEruptive Xanthomas -generally associated with-generally associated with hypercholesterolemiahypertriglyceridemia
  • 24.  Aldosterone ◦ C21 derivative of cholesterol ◦ Promotes renal  Sodium retention  Potassium excretion Glucocorticoids (cortisol) ◦ Starvation  Hepatic gluconeogenesis  Muscle protein degradation  Adipose lipolysis Adrenal androgens ◦ Dehydroepiandroterone (DHEA)  Precurser to potent androgens in extra- adrenal tissues

×