SM7 Flashcards
(23 cards)
How do we get LC FA into the mitochondria for beta oxidation?
They must be activated by acyl CoA synthetase to FA acyle CoA (req. equiv of 2 ATP) and then it is transferred across outer membrane by CPT I. Coupled with that transfer is exchange of COA for carnitine to form fatty acylcarnitine. This is translocated across inner membrane using carnitine acylcarnitine translocate. Then it is acted on by CPT II to reform fatty acyl coA and beta oxidation can now happen.
How do short and medium chain FA cross?
They cross channels in outer membrane and then they cross inner membrane by MCT and they are activated to FA acyl coA once in the matrix.
In beta oxidation what are the four steps to shorten FA by 2 C at a time?
An oxidation that produces FADH2, a hydration step, an oxidation that produces NADH, and a thiolytic cleavage that releases one molecule of acetyl CoA
how does beta oxidation of odd and even chain FA differ?
Even numbered carbon chains, the four steps are repeated until the final four carbon fatty acid is cleaved to 2 acetyl CoAs.
Odd chain fatty acids undergo β-oxidation to a 5 carbon fatty acyl-Co A followed by cleavage to acetyl-CoA and propionyl-CoA. The propionyl-CoA (3C) is converted to succinyl-CoA and oxidized in the TCA cycle.
How does beta oxidation in peroxisomes differ from that in mitochondria?
The FAD is still used as original electron acceptor but then it is immediately re-oxidized using oxygen as electron acceptor to form hydrogen peroxide with no net yield energy. The hydrogen peroxide is then detoxified by catalase.
What happens in alpha oxidation for branched long chain FA.
The fatty acid is shortened to a C8 fatty acid in the peroxisome which is then transferred to mitochondria for complete oxidation.
What happens in omega oxidation in the ER?
ω methyl group (farthest from the alpha carbon) is oxidized to an alcohol by an enzyme that uses cytochrome p450, O2, and NADPH. Dehydrogenases then convert the alcohol to a carboxylic acid producing a dicarboxylic acid. These dicarboxylic acids are oxidized by β-oxidation to compounds that are 6-10 carbons long and water soluble. These are then released to the blood, oxidized as medium chain fatty acids or excreted in urine as dicarboxylic acids.
How are ketone bodies acetoacetate and 3-hydroxybutryate used as a fuel source in peripheral tissues?
They are oxidized to acetyl CoA by the same enzymes used in β-oxidation and subsequently fully oxidized in the TCA cycle. Succinyl-CoA is used as the CoA donor to convert acetoacetate to acetoacetyl-CoA
What happens in alcohol oxidation in the liver?
It is metabolized in the liver by alcohol dehydrogenase (ADH) to acetaldehyde. Most of the acetaldehyde is metabolized to acetate by acetaldehyde dehydrogenase (ALDH). The acetate can be activated by coenzyme A and oxidized in the TCA cycle or used for fatty acid synthesis.
How was disulfiram used for alcoholics?
Since it blocks ALDH it causes buildup of acetaldehyde which makes the person feel really poorly and negatively reinforces alcohol intake.
What happens in FA synthesis?
conversion of glucose to cytosolic acetyl CoA
What regulates acetyl coA carboxylase (which converts acetyl coA to malonyl coA in FA synthesis)?
Upregulated by citrate. Downregulated by too much palmitoyl CoA (product of FA synthesis).
When energy levels are low ATP will phosphorylate the AMP-activated protein kinase to inactivate the acetyl coA carboxylase. When insulin (which is high when glucose is high) is high it will phosphorylate the acetyl coA carboxylase to activate it again.
What inhibits CPT I (which is used in FA oxidation)?
Malonyl CoA (formed during FA synthesis?
What happens in FA synthesis of C16 palmitate by FA synthetase which has 7 catalytic sites?
You have reduction, dehydration, reduction using NADPH as the electron donor. To elongate from palmitate we go through steps of condensation, reduction, dehydration, reduction.
In humans what is the farthest place we can desaturate (put a double bond)?
C9. Involves cytochrome b5, molecular oxygen and NADH
Why do people on keto-diet get acetone breath?
They use ketone bodies for energy and one of the final steps is when acetoacetate spontaneously converts to acetone with loss of CO2.
Where does acetyl CoA for ketone body synthesis come from?
Betoxidation of FA.
Under starvation when fat is gone we break down muscle and use ketogenic AA to form ketone bodies. T/F
True
How do liver vs adipose tissue differ in forming Glycerol 3-P for synthesis of triacylglycerols?
In liver, glycerol-3-P can be made from either glycerol by glycerol kinase, or by the reduction of dihydroxyacetone phosphate produced by glycolysis.
Adipose tissues lack glycerol kinase and must reduce dihydroxyacetone phosphate. Thus, adipose tissue can only synthesis triacylglycerols when glycolysis is active, that is, in the fed state.
How are triacylglycerols synthesized?
Two fatty acids are added to glycerol-3-P to produce phosphatidic acid. The phosphatidic acid is then dephosphorylated to diacylglycerol and the third fatty acid is added. (All of the fatty acids are added from fatty acyl-CoA activated molecules). The products can either be converted to VLDL and transported in blood or converted to adipose tissue.
There are two ways to make phospholipids for membranes from phosphatidic acid.
1) The phosphatidic acid is leaved to diacylglycerol, which reacts with activated head group (CDP-choline or CDP-ethanolamine) to form phosphatidylcholine and phosphatidylethanolamine (Phosphatidylserine formed from phosphatidylethanolamine by exchange of serine for ethanolamine).
OR
2) Phosphatidic acid reacts with CTP to form CDP-diacylglycerol, which reacts with phosphatidylglycerol to form cardiolipin, reacts with inositol to form phosphatidylinositol, or reacts with glycerol-3-phosphate to form phosphatidylglycerol.
How do statins work to prevent synthesis of cholesterol?
They block HMG-CoA Reductase so it cannot reduce HMG-CoA (formed from acetyl CoA and acetoacetyl CoA) to mevalonate.
What kind of molecules are products of cholesterol and isoprenoid synthesis?
Heme A, dolichol, Ubiquinone, steroid hormones, bile acids and vitamin G
