Digestion of lipids depend on the _______ in the TAG.
- Length of fatty acids
* Lingual and gastric lipase present in tongue and stomach to digest short and medium chain FA in TAG
The major lipids present in human diet are?
- Triacylglycerols (TAG)
- Plant and animal sources
- TAGs hold 100,000 kcal of energy, glycogen only 600 kcal, glucose 40
Suspension into small particles in the aqueous environment is the process of?
•Emulsification (opening the molecule and exposing to the enzyme)
Action of Bile Salts
- Fats are emulsified by bile salts in small intestine
- Are amphipathic
- Contraction of gall bladder release bile salts and other pancreatic enzymes is stimulated by the gut hormone cholecystokinin*
Pancreatic Lipase
- Emulsification greatly increase surface area of fats
- Become the substrate of pancreatic lipase
- Secretin released in response to acidic material, causes release of bicarbonate which increase the pH to 6, optimal for intestinal enzymes
- Digest all lengths of FA, forms FA and 2-monoacylglycerol (2-MAG)
Pancrease also produces _______ which removes FA from ________. And __________ which removes FA from ___________.
- Esterase
- Cholesterol esters
- Phospholipase A2
- Phospholipids
Short and medium chain FA (C4-C12) are absorbed into ________.
- Intestinal epithelial cells
* Enter portal blood and transported into the liver bound to serum albumin
Long chain FAs and 2-MAGs are __________ and emulsified by bile salts.
- Packaged into micelles
* Lipids are absorbed across microvilli, bile salts are left in gut
Synthesis of Chylomincrons
- Within intestinal cells, FA and MAGs are condensed to from TAG (in smooth ER)
- Then packaged into chylomicrons which contain protein and phospholipids
- Also contain cholesterol and fat soluble vitamins
- Major apoprotein is B48, made in RER
____________ are secrete by intestinal epithelial cells by exocytosis into lymphatic system.
- Nascent chylomicrons
- Enter blood via thoracic duct
- Accept proteins from HDL within lymph and blood, convert to mature chylomicrons
- ApoE and ApoCII most imp.
____ recognized by receptors on surface of liver cells allowing endocytosis.
- ApoE
* Risk factor in Alzheimer’s
______ activates lipoprotein lipase present on capillary endothelial cells in muscle and adipose tissue which digests chylomicrons.
•ApoCII
3 steps in Utilization of FA as Fuel
- Mobilization: TAGs broken to FA and glycerol, released from aidpose tissue and transported to energy requiring tissue
- Activation: FA must be activated and transported into mito
- Degradation: Stepwise breakdown of FA into acetyl CoA which is then processed in TCA cycle
Mobilization of FA from adipocytes
- Glucagon and Epinephrine come in–>ATP converted to cAMP–>Activates Protein kinase A–>Activates Perilipin and HS lipase
- ATGL-adipose triglyceride lipase: activated removes one fatty acid
- Insulin important for keeping blood glucose levels normal
Fatty Acid is used for energy production via ________.
•ß-oxidation*
FA activation occurs in the ________.
- Cytosol (primed with CoA)
- Carnitine shuttle: carries long-chain FA CoA across mito membrane
- ß-oxidation primarily occurs in mito matrix
First reaction in any FA metabolism:
- Acyl-CoA synthetase*
- traps FA in cells
- Makes it metabolically active
- PP hydrolysis makes it irreversible
- In cytoplasm (ER or outer mito membrane)
FA ß-oxidation in mito matrix:
- Oxidation-hydration-oxidation-Thyiolysis
- FADH2 = 1.5 ATP NADH2 = 2.5 ATP
- Acetyl-CoA = 10 ATP citric acid cycle, Acyl CoA shortened by 2 Cs
Energy yield of FA ß-oxidation in mito matrix:
- 28 ATP –> 7 repetitions of the ß-oxidation spiral
- 80 ATP –> TCA cycle (8 Acetyl CoA, 7 FADH2, 7NADH, 7H+)
- 106 ATP generated!
Unsaturated and Odd chain FA degradation
- Requires 2 additional enzyme: isomerase and reductase
- Odd handled by isomerase, even by both
- Odd give rise to propionyl CoA (converted to Succinyl CoA) and acetyl CoA
Need an _______ to convert cis into trans.
•Isomerase
“Fats burn in…..”
•The flame of carbohydrate”**
Formation of Ketone bodies
•Acetoacetate breaks down into D-3-hydroxybutyrate and acetone
Diabetic Ketosis
- OAA (oxeloacetate) level drops
- CAC slows
- Free FA are released
- Ketone bodies form
- Blood pH drops
- Coma and death result
