Review Flashcards on Fat and Cholesterol

Fat Synthesis and Storage

• Adipose tissue can resynthesize fat by combining fatty acids with glycerol.

• The liver converts excess carbohydrates into acetyl CoA, which is then used for fatty acid synthesis and converted into triacylglycerol for distribution via lipoproteins.

Fatty Acid Synthesis Pathway

• Excess acetyl CoA in liver cells signals storage.

• Citrate is transported into the cytosol to produce acetyl CoA.

• Malonyl CoA production is the rate-limiting step.

• Palmitate, a fatty acid, is generated with the addition of electrons via NADPH.

• Palmitate is activated with CoA and combined with glycerol-3-phosphate to form triacylglycerol in the liver.

Lipoproteins

• Triacylglycerol is packaged into lipoproteins for transport.

• Lipoproteins consist of triacylglycerol, phospholipids, cholesterol, cholesterol esters, and proteins.

• Very low-density lipoproteins (VLDL) are rich in fat.

• Lipoproteins transport hydrophobic molecules in the bloodstream to power muscles via fatty acid cleavage by lipoprotein lipase or for triacylglycerol resynthesis in adipose tissue.

• Proteins on the lipoprotein surface direct it to its target.

• Phospholipids encapsulate hydrophobic molecules with their hydrophilic head groups and hydrophobic tails.

Regulation by Insulin and Glucagon

• Insulin:

  • Produced in response to eating to store glucose as glycogen.

  • Stimulates adipose tissue to take in glucose and fatty acids for storage.

  • Glycerol-3-phosphate for triacylglycerol synthesis comes from glucose via glycolysis.

• Glucagon:

  • Signals the need for fuel in a fasting state.

  • Activates protein kinase A (PKA) via a second messenger.

  • PKA phosphorylates hormone-sensitive lipase to break down stored fat.

Glucagon Receptor and Drug Design

• The glucagon receptor is a G protein-coupled receptor.

• These receptors are critical for drug design as they mediate cellular responses to external stimuli.

• Binding of glucagon causes a conformational change, activating adenylyl cyclase to produce cyclic AMP (cAMP).

• cAMP activates protein kinase A (PKA).

• Adenylyl cyclase converts ATP to cyclic AMP, a stable signaling molecule.

• Cyclic AMP activates protein kinase A, which phosphorylates hormone-sensitive lipase and perilipin to facilitate fat breakdown.

• Fatty acids are released, bind to albumin proteins, and are transported to muscle cells for beta-oxidation.

Cholesterol

• Essential for cell membranes and is a precursor for bile salts and hormones.

• It has both hydrophobic and hydrophilic properties due to its hydroxyl group (amphiphilic).

• Obtained from diet and produced by the body but not used as an energy source.

• Excreted via bile salts in the gastrointestinal system.

• Transported in lipoproteins due to its insolubility in water.

• High levels are associated with heart disease.

Lipoprotein Structure

• Inner core contains triacylglycerol and cholesterol esters.

• Phospholipids and cholesterol associate with the surface.

• Apoproteins (address markers) determine lipoprotein fate.

Lipoprotein Classes

• Classified by density: chylomicrons, VLDL, IDL, LDL, and HDL.

• Chylomicrons transport dietary fats from the intestine to the liver and other tissues. Fatty acids are removed by lipoprotein lipase.

• Smaller molecules are taken up by the liver.

• VLDL (endogenous pathway): produced in the liver to deliver fats and cholesterol esters. As they travel through the bloodstream, fatty acids are removed resulting in LDL.

• Sure!

  - VLDL transports triglycerides (which contain fatty acids) from the liver to tissues for energy or fat storage. As it sheds triglycerides, it converts into LDL.

  - LDL mainly delivers cholesterol to cells but can contribute to plaque buildup in arteries if excessive.

  - Fatty acids impact these lipoproteins—saturated fats raise LDL, while unsaturated fats (like Omega-3) improve balance and heart health.

  • idl is temp carrier in lipid transport chain etween vldl and ldl

LDL and Cholesterol Uptake

• LDL binds to LDL receptors on cells, and cholesterol is utilized in membranes via endocytosis.

• Excess cholesterol in cells leads to the removal of LDL receptors, increasing LDL levels and oxidation in the blood.

• Oxidized LDL is consumed by macrophages, forming foam cells that accumulate on artery walls, leading to plaque formation.

HDL (high-density lipoprotein) and Cholesterol Removal

• HDL removes cholesterol from cell membranes and converts it to cholesterol esters.

• HDL transfers cholesterol esters to other lipoproteins and they are taken up by the liver.

• This reduces cellular cholesterol, promoting LDL receptor expression and LDL clearance.

• HDL is considered "good cholesterol" as it reverses cholesterol buildup.

Risk Factors for Coronary Heart Disease

• High LDL and low HDL levels increase the risk.

• The Framingham Heart Study monitors risk factors for coronary heart disease.

Cholesterol Synthesis

• Synthesized (generated) from acetyl CoA via mevalonate, isoprene, and squalene.

• HMG CoA reductase is a key regulatory enzyme.

• Regulated by phosphorylation and cholesterol levels (product inhibition).

• High cholesterol levels can reduce sensitivity to negative feedback mechanisms (prevent enzyme function/produced).

Statins as HMG CoA Reductase Inhibitors

• Statins block the active site of HMG CoA reductase, reducing cholesterol production. (direct effect of statins)

• Reduce VLDL production and increase LDL receptor production in the liver. (in direct effect of statins)

• Side effects include muscle aches.

Personal Data

• Data showing the effect of statins on personal cholesterol levels and ten-year risk of death.

Here are some key takeaways from the provided note on fat synthesis and storage, useful for exam revision:

1. Fatty Acid Synthesis: Understand how excess acetyl CoA is converted to fatty acids, with malonyl CoA production being the rate-limiting step.

2. Lipoproteins: Know the different types (VLDL, LDL, HDL), their composition, and their roles in transporting fats and cholesterol.

3. Insulin and Glucagon: Understand how these hormones regulate fat storage and breakdown.

4. Cholesterol: Remember its role in cell membranes, its transport via lipoproteins, and the implications of high LDL and low HDL levels.

5. HMG CoA Reductase and Statins: Know how cholesterol synthesis is regulated and how statins inhibit HMG CoA reductase to lower cholesterol levels.