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
what’s the firs mechanism of the synthesis of phospholipids?
A head group combines to CTP to give CDP-head group complex.
A phosphatase removes a phosphate from a phosphatidic acid making diacylglycerol
The CDP-head group and the diacylglycerol combine giving a glycerophospholipid releasing a CMP
Makes:
-phosphotidylcholine
-phosphotidylethanolamine
Indirectly: the serine is added to phosphotidylethanolamine to make phosphotidylserine
What is mechanism 2 of phopholipid synthesis
Phosphatidic acid, two phosphates are removed and is added to CTP.
CDP-Diacylglycerol connects to the head group with release of CMP
Giving glycerophospholipid
Makes:
- phosphatidylinositol
- cardiolipin
What two phosphotidyl’s can be interconverted and by what process?
Phosphotidylserine and phosphotidylethanolamine
PS -> PE by decarboxylation
Methylated PE can form phosphtidylcholine (PC)
How much of the total body weight is cholesterol? What is cholesterol a precursor for?
0.05%
Precursor for:
- bile acids and bile salts
- vitamin D
- steriod hormones: progesterone, aldosterone, cortisol, testosterone, estradiol
What’s the rate limiting step of cholesterol synthesis?
Acetyl CoA to mevalonate by NADPH and HMG CoA Reductase
How is the 27 carbons substance of cholestorol reached? What step fuses the the rings?
Pyrophosphates add to the mevalonate 5 times to give 27 carbons.
Several squalene enzymes fuse the rings
ACAT esterfies the cholesterol giving cholesterol ester
What drug targets hog-coa reductase and stops cholesterol synthesis?
Statins, lovastatin
VLDL
Very low density lipoprotein
ApoB-100, ApoC-II, ApoE
NOT
What apoproteins do chylomicron have?
ApoB-48
ApoC-II
ApoE
What is IDL and LDL relation of VLDL?
It’s a gradient of apoproteins and cholesterol level in the lipoprotein vessel
IDL loses ApoC-II with less triacylglycerols and more cholesterol esters
LDL lost bot ApoE and ApoC-II only retains ApoB-100. Way less TAGs and more cholesterol esters
Other than being “good cholesterol” how is HDL different than the rest?
The smallest most dense particle with high protein and phophlipib content,
ApoA-I
ApoE
ApoC-II
Donates E and C-II to Nascent chylomicrons
How is fat mobilized in adipose tissue?
Epinephrine or glucogon bind a g-protein receptor and activate adenylate cyclase which activates cAMP
cAMP activates PKA
PKA phosphorylates both Perilipase and HS Lipase
Perilipase activates ATGL which removes a FA from a TAG giving a DAG
HS Lipase removes a FA from the DAG and gives MAG
MAG lipase removes the final FA giving Glycerol and FA
The Glycerol goes off to the liver to be acted on by Glycerol Kinase
-feeds into glycolysis, gluconeogenesis or TAG synthesis
Fatty Acids get into other tissues for Beta-Oxidation
