Lipid Metabolism Flashcards
What are the 2 main types of plasma membrane lipids?
- Phospholipids
- Glycolipids
What are the components of glycerophospholipids?
Most abundant lipid in cell membranes
Glycerol (a 3C sugar alcohol)
Phosphate group
2 Fatty acid chains (unsaturated or saturated)
What are the components of sphingolipids or sphingomyelin?
Sphingomyelin:
Phospholipid
Sphingosine backbone (1 fatty acid chain included as part of structure)
2nd Fatty acid chain
Phosphate group + Choline
Sphingolipid:
Glycolipid
Sphingosine backbone (1 fatty acid chain included as part of structure)
2nd Fatty acid chain
Oligosaccharide
Describe the metabolism of omega-3 or omega-6 fatty acids to form eicosanoids.
Ceramide
Sphingosine + Fatty Acid
Sphingomyelin
Ceramide + Phosphocholine
Glycolipid
Ceramide (Sphingosine + Fatty Acid) + Carbohydrate
Describe the metabolism of omega-3 or omega-6 fatty acids to form eicosanoids.
- 3 metabolic pathways
- Cyclooxygenase
- Lipoxygenase
- Epoxygenase
- Converted into eicosanoids (lipid signaling molecules)
What is the function of phospholipase enzyme?
- Phospholipase 2
- Releases fatty acids & hydrolyzes phospholipids from the membrane
- Triggered with inflammatory response
What are the 3 main classes of eicosanoid synthesizing enzymes?
- Cyclooxygenase
- Lipoxygenase
- Epoxygenase
What are cyclooxygenases?
What do they synthesize?
COX:
- Target of NSAID’s
- Cyclize lipids
- Form prostaglandin’s (omega-3 or omega-6)
- Prostaglandin’s = Pro-inflammation
- Trigger to protect cells from further injury/inflammation
- 2 isoforms
Chronic inflammation = bad
What are NSAIDS?
Which class of enzymes do they inhibit?
- Nonsteroidal anti-inflammatory drugs
- Block formation of prostaglandins via pro-inflammatory pathway
- Inhibit COX-1 and COX-2 enzymes
- Reduce production of prostaglandins and thromboxanes
- Reduce pain, fever, and inflammation
- Side effects bc they block the actions of the housekeeping enzymes too (COX-1)
What is the major difference between COX-1 and COX-2?
COX-1:
- Constitutive, expressed in most tissues
- Physiological & homeostatic role
- Cell signaling
- Housekeeping functions
- Lots of COX-1 when you are in a healthy state
COX-2:
- Inducible!
- Expressed in inflammation & trauma
- Found in immune cells
- Induced by cytokines
- Maintains inflammation
Explain how low dose aspirin works.
Describe VLDL, LDL, and HDL
VLDL:
- Very low density lipoprotein
- Contains a small amount of cholesterol
LDL:
- Low density lipoprotein
- Risky for organisms
- Transmits much of cholesterol in the blood
HDL:
- High density lipoprotein
- Less cholesterol than LDL and more amounts of proteins
- Indicator of good health
How are lipid metabolites generated? How do they elicit their action?
- Generated from Omega-3 and Omega-6 fatty acids
- Short-lived
- Act locally on nearby cells
- Activate specific GPCR’s and nuclear receptors
- Control local inflammation to injury
What is the function of the phospholipase enzyme?
- Phospholipase 2
- Breaks open fatty acid
- Releases fatty acids & hydrolyzes phospholipids from the membrane
- Allows for formation of eicosanoid
- Triggers inflammatory response
What are cyclooxygenases?
What do they synthesize?
They make prostaglandins
Target of NSAIDs
Cyclize lipids
Form Omega-3 or Omega-6 prostaglandins
Prostaglandins = PRO-INFLAMMATION
COX triggers pro-inflammatory response to prevent cells from further injury/inflammation
What is the major difference between COX-1 and COX-2?
COX-1:
- Constitutive, expressed in most tissues
- Physiological & homeostatic role
- Cell signaling
- Housekeeping functions
- Lots of COX-1 when you are in a healthy state
COX-2:
- Inducible!
- Expressed in inflammation & trauma
- Found in immune cells
- Induced by cytokines
- Maintains inflammation
What are NSAIDS?
Which class of enzymes do they inhibit?
- Nonsteroidal anti-inflammatory drugs
- Block formation of prostaglandins via pro-inflammatory pathway
- Inhibit COX-1 and COX-2 enzymes
- Reduce production of prostaglandins and thromboxanes
- Reduce pain, fever, and inflammation
- Side effects (gastric/ulcers/bleeding) bc they remove the housekeeping enzymes too
Explain how low dose aspirin works.
- Aspirin is an irreversible inhibitor of COX
- Blocks COX-1 in the platelets
- Short ½ life
- Reduces the ability of blood to clot→ doesn’t eliminate it!
- Makes platelets less sticky
- Decreases heart attacks and stroke in people with already narrowed blood vessels
What are COX-2 inhibitors?
What are their advantages over COX-1 inhibitors?
COX-2 Inhibitors:
Target inflammation and pain response
Freedom from GI side effects and doesn’t take away housekeeping functions
Can cause cardiovascular problems due to imbalance of good/bad prostaglandins
What class of lipid mediator does lipooxygenase synthesize?
Leukotrienes
What are leukotrienes?
- Produced via lipoxygenase pathway from arachidonic acid
- Pro-inflammatory pathway
- Originated in leuklpcytes but now seen in mast cells, platelets and macrophages in response to immunologic stimuli
- 100X stronger than prostaglandins
- Responsible for inflammation and mucous secretion in later stages of allergic response
