Biochem Olson
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- 2 domains of fatty acit
-
carboxylic and hydrocarbon
the COOH portion is the reactive portion - unsaturated fatty acid
- has a carbon double bond in the hydrocarbon chain. the hydrocarbon kinks so the differing structure differs its function
- Where is energy stored in the lipid?
- in the fa bc hydrocaron chain is not oxygenated so it can store energy
- Describe the structure of triacylglycerol
- 3 fatty acids bonded to a glycerol backbone thru ester linkages
- How is triacylglycerol handled in the intestines?
- food in tummy. Bile released from GB and bile emulsifies fat. the smaller pieces of fat can then come into contact with lipase. Lipase breaks down the fat into 2 fa, 2 monoacylglycerol, and bile. this crap forms micelle. the micelle can approach the brushboader of intestine to be taken up by epithelial intestinal cells so fat gets into cell and reforms triacylglycerol. Tyiacylglycerol uses lipoprotien particle called chylomicron to leave cell and enter lymph. it is the pu by caps and carried to tissues. on BV surface, lipoprotein lipases degrade the triacylglycerols into 2 fa and 2 monoacelyglycerol before entering body cell. the fa can be used to form energy and the glycerols can go thru glcolytic pathway to form energy
- What activates the lipoprotein lipases on the BV?
- Apo CII protein on the chylomicron
- largest lipoprotein particle in blood
- chylomicron
- parts of chylomicron
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inner is triaclgycerols and cholesteryl esters
outer is phospholipids
Apoliproteins are the sturctural proteins on surface
B48 defines chylomicron. it is protein from intestinal cells
ApoCII activates lipoprotein - apoolipoproteins on chylomicron
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B48 defines chylomicron
ApoCI
ApoCII involved in activating lipoprotein lipase - Describe intestinal lipase
- in SI degrade triacylglycerols into 2 fa and glycerol
- describe lipoprotein lipase
- This lipase is on the surface of BV and is activated by the ApoCII protein on the chylomicron. It breaks down triacylglycerol into 2 fa and 2 monoacelyglycerols; it does this by cleaning out the inner part of the chylomicron and the outer part shrinks.
- describe hormone sensitive lipases
- catalyzes the hydrolysiss of the ester linkages of triacylglycerols and is located in the membrane of adipocyte cells
- What is a chylomicron? where is it made and what is its function?
- Dietary triacylglycerols packaged with dietary cholesterol and apoplipoproteins and it is made in the intestinal epithelial cells. its function is to aid in th transport of FAs to lymph and enter BS to be carried to tissues
- ApoA-1
- Associated with lipoprotein HDL. ApoA-1 activates LCAT and interacts with ABC transporter
- ApoB100
- Associated with lipoprotein VLDL, LDL. ApoB100 binds to LDL receptor (LDL ligand)
- ApoCII
- Associated with lipoproteins Chylomicron, VLDL, HDL. ApoCII activates lipoprotein lipase
- ApoCIII
- associated with lipoproteins chylomicrons, VLDL, HDL. ApoCIII inhibits lipoprotein lipase
- ApoE
- Associated with lipoproteins chylomicrons, VLDL, HDL. ApoE trigger clearance of VLDL and chylomicron remnants
- What happens if there is a problem with ApoB 100?
- ApoB 100 is on LDL. If problem with it, LDL cannot be cleared from the body
- How are lipids packaged to be transported in hydrophillic environment of plasma?
- as lipoprotein particles
- classes of lipoproteins particles
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chylomicron
LDL-Derived from VLDL particles that have transported all of their triacylglycerol to the periphereal tissues. they deliver cholesterol to tissue "bad cholesterol"
VLDL-package fat in the liver to shipped to the rest of the body
HDL-has ApoA-1,ApoC-1, and ApoC-II associated with it. Its function is to PU cholesterol in peripherial tissue and return it to the liver. "good cholesterol" - smallest lipoprotein
- LDL bc lost all triglyceride
- signature protein of LDL
- ApoB-100
- How are FA activated?
- by forming a fatty acyl CoA ester
- when triacylglyerols are broken down, what are the products?
- free fatty acids and glycerol
- What is the rate limiting step in beta oxidation of fatty acids/
- entry of fatty acyl CoA into mitochondria bc when we run out of free CoA we can no longer metabolize free FA. If the enzyme to form the Fa-carnitine bond is inhibited transport cant occur, thats how this process can be regulated
- How does transport of FaCoA to mitochondria for beta oxidation occur?
- fa binds to CoA in cytosol but need ATP. this is the rate limiting step. the Fatty acyl CoA has a esterbond that holds the energy and this is the metabolic starting point. Problem the metabolic enzyme that utilize fa are in the inner mitochondria membrane. So FaCoA transesterifes to carnitine on outer mit. membrane and CoA is released into cytosol. the acylcarnitine shuttles into matrix through carrier protein. For every acylcarnitine going in mitochondria, one free carnitine must come out.Once transported to inner mit. matrix The CoA binds the acyl and the carnitine is released.
- What products are directly made from the beta oxidation of fatty acids?
- If you start out with fatty acid with C16 (palmitol) end up with (C14) Acyl Co A and Acetyl CoA. the alpha carbon and carbonyl carbon of the fatty acyl-CoA is chopped off. Many NADH and FADH are releaed.
- How many carbons are removed through each cycle of beta oxidation?
- 2 carbons
- After beta oxidation, acyl CoA and Acetyl CoA are formed. Where do they go?
- Acyl CoA goes back to the first step to release more carbons and the acetyl CoA goes to Krebs to be further oxidized.
- Beta oxidation has many intermediate steps. Why?
- to provide an unstable intermediate so the carbons can be cleaved off.
- In what tissue and under what physiologic condions are ketones synthesized?
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In mitochondrial matrix of liver cells the Acetyl CoA is metabolized to ketone bodies when the rate of beta-oxidation exceeds the rate at which acetyl CoA is able to be metabolized thru the TCA cyle. these ketone bodies are used as substitues for energy.
Ketons are also overproduced under conditions when gluconeogenisis is activated like during starvation and uncontrolled diabetes - Function of Ketosis
- Frees up CoA
- end products of ketosis
- ketone and an acid. the acid can release a proton and cause acidosis so w/hi keton in blood you can get ketoacidosis
- Problem with reabsorbing ketones.
- Can reabsorb em so pee out ketones but ketones carry proton so changes pH in plasma. also water and electrolytes are lost bc leave with ketones
- In Fatty acid synthesis, what is malonyl CoA, and what functions does it have in tissue/
- Malonyl CoA is an acetyl CoA plus a carboxyl. It is a regulator that causes a switch from carbohydrate metabolism to fat metabolims. It is used to make new fa from excess in the liver. It also inhibits the carnitine shuttle to prevent FA from entering mitochondria for beta oxidation. It is synthesized from Acetyl CoA i nthe cytosol by Acetyl CoA Carboylase enzyme
- Describe Acetyl CoA carboylase
- made of 3 protein units assembled in the cytosol and requires biotin to function
- Malonyl CoA is synthesized from acetyl CoA in the cytoplasm. Where does the acetyl CoA come from that is used for maikin malonyl CoA?
- The acetyl CoA comes from the cytosol
- Why is fatty acid oxidation regulated?
- so that fat is being burned only when it is needed for energy
- What inhibits carnitine shuttle to prevent FA from entering mit. matrix to be beta oxidized?
- malonyl CoA
- What regulates the activation of Acetyl CoA carboxylase?
- malonyl CoA synthesis
- What is the endproduct of complete functioning of the fatty synthase complex?
- palmitate (16;0)
- During fatty acid synthesis how doe fa chain grow/
- By 2 carbon units at a time provided by malonyl CoA
- What are eicosanoids?
- regulatory lipids
- Names and structures of essential dietary Fatty acids
-
Both are polyunsaturated fatty acids
Linoleate (18:2) Delta 9,12
so basically 18C with 2 double bonds at 9 and 12 C.
Linolenate-alpha version 18:3 delta 9,12,15 and gamma version 18;3 delta 6,9,12 - What are dietarily fatty acids used for?
- linoleate is used to synthesize 20 carbon fatty acids by fatty acid elongation reactions. It can also be used to make arachidonate, this is the only way arachidonate can be made. Arachidonate is a precursor for the eicosanoids
- Why are linolenate and linoleate dietarily essential?
- bc we do not have the enzymes to carry out unsaturation past the 9th carbon
- Types of eicosanoids
- prostaglandin and leukotriens
- What products of the cyclooxygenase pathway do in the body/
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Prostaglandins-COX-1 regulate gastric mucin secretion and other types COX-2 mediate inflammation, pain and fever.
Thromboxanes-induce constriction of BV and platelet aggregation in the early steps of blood clotting - What does COX enzymes do?
- the cyclize PUFA chanin and add O2.
- What do products of the lipoxygenase pathway do in the body?
- they crete leukotrienes what are linear derivatives as opposed to prostoglandins and thromboxane which are cyclic pathways. Leukotrienes mediate immediate ypersensitity. Excess leukiotrienes can lead to allergies, hay fever, and asthma.
- How can both prostaglandins and leukotrienes be inhibited?
- inhibit phospholiapse A2 to prevent release of arachidonate by cortisone so neither COX pathway now lipoxygenase pathway can occur
- mehanism by which cortisione and non steroidal anitinflam. drugs can inhibit the formation of prostaglandins and leukotrienes. What are the similiarities and differences?
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cortisone inhibits the release arachidonate from phospholipids so this prevents prostaglandins and leukotrienes from forming.
Non steroidal drugs either mimmick the substrate to inhibit production (naproxen and IBprofen) or they acetylate the essential serine residue at the active sit of the COX enzyme, known as covalent modification (Aspirin) - How is cholesterol synthesized? What is rate limiting step/
- formation of mevalonate from HMG-CoA is the rate limiting step. the enzyme involved with this is HMG-CoA reductase. Melvonate is made from acetate and then melvonate is converted to 2 activated isprenes thru series of phosphorylation. 6 isoprenes condense to form squalenen and squalene converts tothe 4 ring steroid nucleus.
- Buildig block of cholesterol
- Isoprene made from acetate
- How is cholesterol eliminated from the body?
- HDL picks up cholesterol in peripheral tissues and brings it back to the liver where it gets turned into bile and is excreted.
- How do cholestrol lowering drugs work?
- By inhibiting the biosynthesis of cholesterol by acting on HMG-CoA reductase by the actual drug looking like cholestrol and shutting the enzyme off
- 2 functions of malonyl CoA
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1. inhibits carnitine acyl transferase so Beta oxidation cant occur
2. substrate lipit for fa biosynthesis in cytosol - where does FA synthesis occur?
- Cytosol
- What activates ACC?
- hi citrate, glucose, carbs, insulin in cytosol activates ACC so malonyl CoA is formed to allow FA synthesis
- What inhibits ACC?
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Lo glucose
Hi glucagon - 4 steps of fa synthesis
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1. condensation of acetyl CoA to a molecule of malonyl CoA
2. Reduce keto group to alchol
3. Eliminate water to form double bond
4. Reduce double bond to form a saturated acyl group
This occurs on fatty acid syntase - Where is acetyl CoA produced?
- in miochondria. Made from pyruvate oxidation and fa beta oxidation
- Where is cholestrol synthesized?
- Cytosol
- two pathways needed to form reducing agents to support lipid biosynthesis
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1. pentose phosphate pathway
2. malic enzyme
Both make NADPH that is NEEDED for lipid biosynthesis - How does Acetyl Co A get into Cytosol?
- If you have alot of citrate and you dont need oxidation bc ATP levels are hi, Citrate goes through inner mit. membrane and into cytosol. In cytosol, Citrate lyases clease Citrate and CoA is released to form Oxaloacetate. The oxaloacetate then forms Malate. The malate can either form pyruvate or go back into inner mit. matrix