fatty acid degration and synthesis Flashcards
What’s the first site of digestion for dietary lipids? And the subsequent? Are these the major sites for lipid digestion in the body?
First site: oral cavity by lingual lipase
Next: stomach with gastric lipase
neither is where most the digestion happens.
Lingual and gastric lipase mainly digest short and medium fatty acids
What is the fate of fat in the small intestine?
Emulsification by bile salts synthesized by the liver but released/stored by the gallbladder.
Breakdown by pancreatic enzymes.
Cholecystokinin stimulated contraction of the gallbladder and release of the enzymes
What is the substrate for pancreatic lipase? What does breakdown by pancreatic enzymes form? (The products)
The substrate is all lengths of fatty acids chains, emulsification allows easier access to the substrate by pancreatic lipase
The products of the lipase is a free fatty acid and 2-MAG
(2-monoacylglycerol)
The pancreatic lipase activity creates an acidic environment, but this is not the optimal pH for enzymatic activity. What is reposible for optimal pH in the small intestine despite pancreatic lipase activity? what other enzymes function in the small intestine for digestion?
Acidic material causes the hormone secretin to be released, this causes release of bicarbonate.
Esterase: digests cholestorol esters
Phospholipase A2: removes FA from phospholipids
All dietary fats go to the liver, how do short and medium chain fats make this trip?
After being digested they are absorbed into the intestinal epithelial cells.
They enter portal blood and transport to the liver while bound to albumin
How to the long chain fatty acids and 2-MAGs make it to their destination? What determines the destination?
They package into micelles along with other lipid soluble molecules like cholesterol, lyso PLs and fat soluble vitamins.
Absorbed into the intestinal cells where the FA and 2-MAGs are reformed into TAGs and packed into chylomicrons along with protiens, cholesterol, phospholipids and vitamins. At this point the only Apo protein present is B48.
Called Nascent chylomicrons, excreted into the lymphatic system by exocytosis and then the blood.
In the blood they accepted Apo proteins from HDL -> mature chylomicrons
Where they go is determined by the apo proteins they got.
What apo proteins are chylomicrons tagged with and where do they send them?
ApoE - liver cells
ApoCII - capillary endothelial cells in muscle and adipose, by lipoproteinase (because chylomicrons cannot go through the PM)
triacylglycerols are stored in adipose tissue, how is it mobilized in times of energy need?
First broken down into FA and glycerol, fatty acids need to be activated by CoA so they can be transferred into mitochondria. Then trade off for carnitine to get into the mitochondrial matrix. CoA is reattached, then beta-oxidation -> Acetyl-CoA
Glycerol delt with by Glycerol kinase to eventually synthesize TAG’s, or feed into glycolysis or gluconeogenesis.
B-oxidation:
- oxidation: FADH2 (1.5 ATP)
- hydration
- oxidation: NADH (2.5 ATP)
- thiolysis: Acetyl-CoA (10 ATP)
What’s the purpose of carnitine in fatty acid oxidation?
It binds to fatty acyl to transport accross the mitochondrial matrix, switches back out for CoA
How is the oxidation of unsaturated fats different than b-oxidation of saturated salts?
Requires 2 extra enzymes: Isomerase and reductase
Odd numbered - isomerase
Even numbered - reductase and isomerase
Why would a person whose trying to lose weight on a no carb diet not be successful? (They are excersizing)
Carbohydrates are the major carbon source for the body, they are used to make Oxaloacetate. If there is none oxaloacetate then the TCA cycle cannot run and FA will not be utilized as Acetyl-CoA through the cycle.
It will instead be used up by gluconeogenesis to make glucose.
Acetyl CoA will instead form ketone bodies
-which will drop blood pH -> ketoacidosis
How are fatty acids synthesized?
Formation of acetyl coa - pyruvate gets broken into OAA and acetyl coa in the mitochondria, leaves mito as citrate, breaks back down.
Acetyl coa is converted to malonyl coa - rate limiting steps - catalyzed by atecylcoa carboxylase (carboxylation)
Malonyl coa donates 2 carbons to the growing fatty acyl until palmitate is made (16:0)
-fatty acid synthase
What is fatty acid synthase?
A large multienyme complex composed of two identical dimers
Both have 7 catalytic activists and an acyl carrier protein.
Arranged in head-to-tail conformation aligned according to a cysteinyl sulfhydral group
Reactions: Condensation Reduction Dehydration Reduction
How is Acetyl CoA carboxylase regulated?
ACC is regulated allosterically, by phosphorylation/dephosphorylation and gene induction or repression
Allosteric reg: (+) citrate (-) long chain fatty acids
Phos/Dephos: Insulin (+), Epinephrine and Glucogon (-)
Gene expression is upreged by high carb/low fat diet
Gene expression is downregged by high fat/low carb diet.
How is fatty acid synthase regulated?
Allosterically by prescense of phosphorylated sugars
Induction repression of gene
- high carb/low fat: increases
- fat fat diet and starvation lowers FAS synthesis
