Cholesterol Flashcards
Cholesterol Facts
Structural Role: Cholesterol is a structural component of membranes.
Essentiality: Not an essential nutrient; all cells can synthesize cholesterol.
Functions: Used for steroid hormone and bile acid biosynthesis in certain cells.
Energy Derivation: Cholesterol is not oxidized or used for energy like other lipids.
Concerns: Excess cholesterol can lead to atherosclerotic plaques, increasing the risk of heart attacks and strokes.
Four Stages of Cholesterol Synthesis
Stage 1: Condensation of 3 acetate groups to form a 6-carbon mevalonate.
Stage 2: Conversion of mevalonate to activated 5C isoprene units, requiring 3 ATPs.
Stage 3: Polymerization of six 5-carbon isoprene units to form a 30-carbon linear squalene.
Stage 4: Cyclization of squalene to form a 4-ring steroid nucleus, involving oxidations and removal or migration of methyl groups.
Synthesis of Mevalonate
Pathway: Mevalonate synthesis is part of the cholesterol biosynthesis pathway.
Location: It occurs in the cytoplasm of the cell.
Steps:
a. Acetyl-CoA is converted to acetoacetyl-CoA by thiolase and further to 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) by HMG-CoA synthase.
b. HMG-CoA is reduced to mevalonate by HMG-CoA reductase.
Regulation: The reduction of HMG-CoA is the rate-limiting and tightly regulated step.
Synthesis of Ketone Bodies
Pathway: Ketone body synthesis (ketogenesis) occurs in the mitochondria of liver cells.
Conditions: Activated during low glucose levels, such as fasting or prolonged exercise.
Steps:
a. Acetyl-CoA condenses to form acetoacetyl-CoA by thiolase.
b. Acetoacetyl-CoA combines with another acetyl-CoA to form 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) by HMG-CoA synthase.
c. HMG-CoA is split by HMG-CoA lyase to produce acetoacetate (a ketone body) and another acetyl-CoA.
Comparison of Synthesis of Mevalonate and Ketone Bodies
Both pathways start with acetyl-CoA and involve HMG-CoA formation, but the end products differ - mevalonate in cholesterol biosynthesis and ketone bodies in ketogenesis. The location and conditions for these pathways are distinct.
Statin Drugs
Definition: Statins are competitive inhibitors of HMG CoA Reductase, commonly isolated from fungi.
Names: Examples include LIPITOR, ZOCOR, Lovastatin, etc.
Statin Drugs Inhibition and Effect
Inhibition: Statins are highly effective at inhibiting HMG-CoA reductase activity.
Effect: Reduced biosynthesis, combined with a low-fat diet, significantly lowers whole-body cholesterol levels.
four lipoprotein particles
Chylomicrons, Very-Low-Density Lipoproteins, Low-Density Lipoproteins, High density LIpoproteins
Chylomicrons
Function: Transport of lipids from the diet.
Density: Lowest-density lipoprotein particles.
Composition: Higher proportion of lipids, lower proportion of proteins.
Very-Low-Density Lipoproteins (VLDLs)
Function: Carry triglycerides (TAGs) from the liver to peripheral tissues.
Density: Higher than chylomicrons but still considered very low-density.
Composition: More lipids, less protein.
Low-Density Lipoproteins (LDLs)
Function: Transport cholesterol from the liver to peripheral tissues.
Density: Lower than VLDLs but still considered low-density.
Significance: High LDL values (>200 mg/dl) are detrimental, leading to cholesterol deposition in tissues and atherosclerosis.
High-Density Lipoproteins (HDLs)
Function: Transport cholesterol from dead or dying cells back to the liver.
Density: Higher than LDLs, considered high-density lipoproteins.
Composition: More protein, less fat.
Significance: HDLs are considered beneficial as they remove cholesterol from tissues.
Homozygous LDL Receptor Deficiency
Genetics: Homozygous individuals (two defective genes).
LDL Levels: 5x normal blood LDL.
Outcome: Develop atherosclerosis and coronary infarction in adolescence
Heterozygous LDL Receptor Deficiency
Genetics: Heterozygous individuals (one mutant gene).
LDL Levels: 2-3x higher LDL.
Onset: Symptoms around age 40.
Link between LDL and Atherosclerosis
Association: Elevated LDL linked to atherosclerosis.
Genetic Impact: Homozygous – early-onset atherosclerosis.
Onset in Heterozygous: Develop symptoms around age 40.
