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91 Cards in this Set
- Front
- Back
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What are fatty acids synthesized from?
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Acetyl CoA
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What is "Fat" synthesized from?
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Fatty acids and glycerol
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Where is fat stored?
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In adipose cells
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What is made from surplus carbohydrate and proteins?
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Acetyl CoA
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What transports acetyl CoA from the mitochondria to the cytosol?
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The citrate shuttle:
Citrate -> malate -> pyruvate shuttle |
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Where in the cell is Acetyl CoA synthesized?
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In the mitochondrial matrix
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What enzyme carries out fatty acid synthesis? where is this reaction carried out in the cell?
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By fatty acid synthase in the cytosol
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Where does the majority of fatty acid synthesis take place?
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In the liver
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Where is the citrate transporter located?
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In the inner mitochondrial membrane
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What is the citrate synthase enzyme's reaction? Where does it take place?
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Acetyl CoA + OAA -> citrate, which takes place in the mitochondrial matrix
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What happens to citrate once it crosses into the cytosol?
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It is lysed by ATP-citrate lyase to form Acetyl Coa and OAA using ATP.
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What happens to the OAA that is produced from the citrate shuttle?
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It is reduced to malate using NADH by malate dehydrogenase.
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What happens to malate in the citrate shuttle?
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It is decarboxylated by malic enzyme using NADP+ to form pyruvate, NADPH and CO2
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What happens to Pyruvate in the citrate shuttle?
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It crosses the inner mitochondrial membrane where it forms OAA using ATP and CO2 by pyruvate carboxylase.
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What products of the citrate shuttle are used in fatty acid synthesis?
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Acetyl CoA and NADPH
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What is the first step in fatty acid synthesis?
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Carboxylating the acetyl CoA to turn it into malonyl CoA
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What is the reaction that forms malonyl CoA?
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Acetyl CoA and Co2 are carboxylated to form malonyl CoA by acetyl CoA Carboxylase using ATP
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What coenzyme is required by Acetyl CoA carboxylase?
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Biotin
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What is the committed step in fatty acid biosynthesis?
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Acetyl CoA carboxylase
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What regulates acetyl CoA carboxylase?
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1. adenylate energy charge
2. hormones 3. allosteric effectors |
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What is the adenylate energy charge?
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The fraction of the adenine nucleotides in a cell that contains a high-energy phosphoanhydride bonds (~P).
*It is a quantitative description of the cell's ~P energy state. |
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How do you calculate the energy charge of a cell?
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E.C. = ([ATP] + .5[ADP])/([ATP] + [ADP] + [AMP])
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What is the energy charge of well-nourished aerobic cells?
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~ 0.9, a high energy charge
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What is the relationship b/e energy charge and acetyl CoA carboxylase activity?
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The higher the energy charge the more active the acetyl CoA carboxylase will be.
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What is Insulin's effect on acetyl CoA Carboxylase?
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Insulin promotes dephosphorylation of acetyl CoA carboxylase via protein phosphatase 24.
*promotes formation of the active form of acetyl CoA carboxylase |
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What are glucagon/epinephrine's effects on acetyl CoA Carboxylase?
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Promote phosphorylation of acetyl CoA carboxylase to its inactive form via cAMP-dependent protein kinase.
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What effect does a low cell energy charge have on acetyl coa carboxylase?
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Stimulates phosphorylation of acetyl coa carboxylase to its inactive form via AMP-activated protein kinase.
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What is the inactive form of acetyl coa carboxylase?
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It exists as a inactive dimer and as active filaments
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What effect does citrate have on acetyl coa carboxylase?
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Citrate facilitates the formation of active filaments, so it activates acetyl coa carboxylase formation by causing the inactive dimers to come together and form a polymer which is the active enzyme.
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What effect do long-chain fatty acyl CoAs such as palmitoyl CoA have on acetyl CoA carboxylase?
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causes the disassembly of the acetyl coa carboxylase polymer to its inactive dimer form.
*so it is a negative feedback loop |
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What is fatty acid synthase?
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A multi-subunit complex on which fatty acid synthesis is carried out. It contains two sulphhydril groups.
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What is attached to the ACP-pantetheinyl sulfhydril group?
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A malonyl group
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What is attached to the cysteinyl sulfhydril group?
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An acetyl group
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What are the two components of fatty acid synthase?
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A cysteinyl SH and a ACP-pantetheinyl SH
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What happens to the acetyl and malonyl groups after they are attached to their SH groups?
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They condense to form a acetoacetyl group that is attached to the ACP-pantetheinyl sulfhydryl.
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What drives the fatty acid synthase reactions to keep going in the forward direction?
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The fact that CO2 is produced in the final step of the reaction which is then exhaled, the removal of the product drives the reaction via le chatelier's principle.
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How many cycles does the Fatty acid synthase reaction go through to generate palmitate?
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7 total cycles
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What is the sequence of reactions that occurs during reduction of the ketone sequence after the synthesis of acetoacetyl-enzyme?
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Two NADPH linked reductions w/ a dehydration in between.
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Where does beta-oxidation occur?
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In the mitochondria
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Where does fatty acid synthesis occur?
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in the cytosol
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What is the importance of the compartmentalization of fatty acid synthesis and beta-oxidation?
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That both processes can proceed in their forward direction w/o substrate cycling.
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How can fatty acids be modified?
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By chain lengthening and by introducing double bonds (desaturation)
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Where do fatty acid elongation reactions take place?
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In the ER
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How is FA elongation carried out in the ER?
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By condensation of palmitoyl CoA w/ malonyl CoA
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What is the function of unsaturated fatty acids?
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Important for regulating the fluidity of TAGs and membrane phospholipids as well as forming cholesterol esters and waxy skin secretions.
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What is the furthest down the FA chain that double bonds can be introduced?
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Carbon 9
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What is used to synthesize eicosanoids?
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polyunsaturated fatty acids
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What are the essential fatty acids?
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Linoleic acid or alpha-linolenic acid
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What does Steaoryl CoA desaturase do? where is it located?
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Located in the ER it introduces a C9 double bond forming oleic acid
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What are triacylglycoerols (TGs/fat) made from?
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Phosphatidic acid
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What is phosphatidic acid made from?
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Actyl CoA and glycerol phosphate or dihydroxyacetone phosphate
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where else do you find dihydroxyacetone phosphate besides TG synthesis?
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Glycolysis
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What are the sources of glycerol phosphate for fat synthesis?
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Glucose and glycerol
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Where is glycerol-P-dehydrogenase located?
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In adipose tissue and in the liver
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Where is glycerol kinase located?
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In the liver
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What does glycerol kinase do?
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Converts glycerol to glycerol-3-phosphate using ATP
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What does glycerol-P-dehydrogenase do?
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Converts dihydroxyacetone phosphate to glycerol-3-phosphate using NADH
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What is phosphatidic acid synthesized from?
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Glycerol phosphate and acyl CoA OR from dihydroxyacetone phosphate
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What is triacylglycerol synthesized from?
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Phosphatidate
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What is the process of phosphatidate synthesis from triacylglycerol?
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Phosphatidic acid is converted to diacylglycerol using water and the enzyme phosphatase
Then triacylglycerol is synthesized from diacylglycerol using SCoA and the enzyme acyltransferase |
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Why store fat and not glycogen?
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Glycogen takes more space and is more polar, so you can store way more TAG than glycogen.
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What do membrane lipid complexes contain?
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1. phosphatidates
2. ether lipids 3. sphingolipids 4. cholesterol |
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What does phosphatidate synthesis begin with?
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Diacylglycerol and phosphatidate
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How are phosphatidylcholine and phosphatidylethanolamine synthesized?
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By transferring activated bases to DAG.
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What provides the activated bases in phosphatidylcholine and phosphatidylethanolamine synthesis?
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CDP derivatives
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How is phosphatidylserine synthesized?
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By exchanging serine for ethanolamine on PE
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How are cardiolipid and phosphatidylinositol synthesized?
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1. DAG is activated to CDP-diacylglycerol
2. Phosphatidylglycerol displaces CMP to yield cardiolipin. 3. Inositol displaces CMP to yield phosphatidylinositol |
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Do sphingolipids contain a glycerol moiety? what is their moiety?
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Nope, their alcohol moiety is sphingosine
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What is the reactive nucleotide in making phosphatidylcholine?
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Cytidine (CTP); which makes the reactive amine which reacts w/ DAG to make phosphatidylcholine (lecithin)
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What is the reactive nucleotide in making glycogen?
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UDP-glucose
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How are CDP-ethanolamine and CDP-choline synthesized?
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By taking ethanolamine or choline => reacting them w/ ATP using ethanolamine kinase or choline kinase, then taking the phosphoethanolamine/phosphocholine and reacting them w/ the reactive nucleotide CTP to yield CDP-ethanolamine or CDP-choline
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How do you make phosphatidylethanolamine or phosphatidylcholine (PC, or lecithin)?
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By taking CDP-choline or CDP-ethanolamine and reacting them w/ DAG, CMP is a byproduct.
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How do you make phosphatidylserine?
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By reacting phosphatidylethanolamine w/ serine, this yields phosphatidylserine and gives off ethanolamine as a byproduct.
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How do you make diacylgylcerol? (DAG)
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1. By taking a long chain fatty acid, reactive it w/ CoA using acyl CoA synthase to give long chain fatty acyl CoA.
2. Then taking long-chain fatty acyl CoA and react it w/ glycerol using glycerol-3-phosphate acyltransferase to give a monoglycerol. 3. The monoglycerol is reacted w/ another long-chain fatty acyl CoA using acyl glycerol-3-phosphate acyltransferase to yield a DAG w/ a phosphate 4. The DAG w/ phosphate is dephosphorylated using phosphatidic acid phosphatase to DAG. |
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What are the "cephalins"?
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1. phosphatidylethanolamine
2. phosphatidylserine |
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What is the difference b/e cardiolipin/phosphatidylinositol synthesis and phosphatidylcholine/phosphatidylethanolamine/phosphatidylserine synthesis?
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In cardiolipin and phosphatidylinositol instead of activating the group (i.e. choline) they activate glycerol instead.
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How are cardiolipin and phosphatidylinositol synthesized?
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1. DAG is activated as CDP-diacylglycerol
2. Phosphatidylglycerol displaces CMP to yield cardiolipin. 3. inositol displaces CMP to yield phosphatidylinositol |
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What is the importance of phosphatidylinositol?
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It can be phosphorylated to form the phosphoinositides like PIP, PIP2 and PIP3
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How are ether lipids synthesized?
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1. An acyl group is esterified to C1 of dihydroxyacetone phosphate
2. the acyl group is displaced by fatty alcohols to produce an ether linkage at C1 3. the keto-group at C2 is reduced by NADPH 4. A fatty acid ester is formed at C2 using Acyl CoA 5. Dephosphorylation at C3 and addition of choline follow. |
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What is the starting substrate of phosphatidalcholine synthesis?
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Dihydroxyacetone phosphate
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What is the clinical importance of phosphatidalcholine?
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The fatty acyl group at C2 can be replaced w/ an acetyl group to yield platelet-activating factor (PAF).
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When is PAF synthesized and released?
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When polymorphonuclear leukocytes (PMNs) are stimulated.
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What processes does PAF mediate?
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1. platelet aggregation
2. hypersensitivity 3. acute inflammatory responses 4. allergic responses 5. anaphylactic shock |
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What does sphingolipid synthesis start with?
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Palmitoyl CoA and serine
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What is produced if you add a NH2 to C2 of sphinganine?
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A dihydroceramide
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What is produced by reacting palmitoyl CoA and serine?
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Sphinganine
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What does desaturation of dihydroceramide yield?
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ceramide
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What does addition of phosphorylcholine to C1 of ceramide yield?
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sphingomyelin
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What does addition of a sugar at C1 of ceramide yield?
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If you added galactose you get galactosylcerebroside; if you added glucose you get glucosylcerebroside
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What does adding an oligosaccharide containing N-acetylneuraminic acid to C1 of ceramide produce?
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Ganglioside
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