Term
| What two enzymes catalyze all the chemical steps required for the synthesis of a C16 FA from acetyl CoA? |
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Definition
| Acetyl Co-A Carboxylase (C2 acetyl-CoA à C3 malonyl CoA) and Fatty Acid Synthase. |
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Term
| What types of FA's can't be synthesized de novo in humans? |
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Definition
| W3 and W6 Polyunsaturated FA's. Desaturases can't cleave double bonds so close to the W end. These FA's are important in the production of eiconisoids. |
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Term
| True or false: Under conditions of net FA synthesis, the main source of acetyl CoA is carboydrate. |
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Definition
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Term
| Explain why FA's are synthesized when glucose levels are high. |
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Definition
| With high glucose, there is high glycolysis. ATP levels are elevated and the rate-limiting enzyme of the TCA cycle, isocitrate dehydrogenase is inhibited. Citrate accumulates and is transported out of the mitochondria into the cytosol to form fatty acids. |
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Term
| How is citrate converted to acetyl CoA? |
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Definition
| Citrate lyase with ATP providing the energy and HS-CoA providing the CoA. |
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Term
| What are the reducing equivalents used in fatty acid synthesis and where do they come from? |
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Definition
| NADPH's are used. They come from the pentose phosphate shunt (2) and the malate transhydrogrenase shuttle (malate to pyruvate and CO2 by way of malic enzyme). |
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Term
| What does Acetyl CoA Carboxylase do and where is it located? |
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Definition
| Catalyzes synthesis of malonyl CoA from acetyl CoA and bicarbonate (using biotin). It's the rate-limiting step in FA synthesis. ACC1 (lipgenic) is found in the liver and adipose tissue and is found in the cytosol. ACC2 (oxidative) is mostly in heart and muscle (some in liver) and is localized in the mitochondria. |
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Term
| What are the five steps in FA synthesis? |
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Definition
| 1) Activation: carboxylation of acetyl CoA (rate-controlling step), 2) Condensation: C=O (formation of B-keto group), 3) Reduction: C-OH (of the B-keto group), 4) Dehydration: C=C (of the AB carbons), 5) Reduction: C-C (of the AB double bond) |
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Term
| True or false: Cells can elongate existing FA's and introduce cis double bonds? |
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Definition
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Term
| Describe the regulatory mechanism for ACC1 activity. (DEFINITELY ON EXAM) |
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Definition
| Monomer form (1 P) is inactive. Polymer form (2 P) is active. Allosteric: Citrate activates. LCFA CoA's inhibit. Covalent: Glucagon, Epinephrine, and Norepinephrine stimulate cAMP and inactivate ACC. Insulin either promotes phosphatase or phosphorylation at a second site to activate ACC. |
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Term
| True or false: Exercise inhibits ACC2 via a transcriptional mechanism. |
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Definition
| True, but it also works through AMP Kinase to inhibit ACC2 enzymatically. Recall inhibition of ACC2 means no FA synthesis. |
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Term
| What is the result of decreased ACC2 activity? |
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Definition
| Decreased ACC2 activity means decreased Malonyl CoA levels which means higher FA oxidation and decreased DAG levels (important in signaling). Recall that Malonyl CoA is what donates 2 C's during each round of FA synthesis. |
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Term
| What is the role of ACP in FA Synthesis? |
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Definition
| ACP (acyl carrier protein) is an integral part of FAS that binds acetyl CoA during priming. It remains until the final step of each round when it is cleaved off yielding the +2 C FA. |
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Term
| Why use malonyl CoA for synthesis? |
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Definition
| Cleavage of bond between two acyl groups is highly exergonic (think also about B-oxidation). When acetyl CoA is added to malonyl CoA, the outmost C is thus cleaved and the reaction is driven forward. |
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Term
| True or false: FA synthesis is only done in the presence of excess energy. |
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Definition
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Term
| Where does elongation occur? |
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Definition
| FA elongation occurs in the ER (main site, uses malonyl CoA as carbon donor) and in the mitochondria (uses acetyl CoA as carbon donor) using elongases. (Therefore palmitate isn't the only product of FA synthesis.) |
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Term
| How are cis bonds introduced? |
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Definition
| Desaturases exist in the ER that require O2 and NADH to add a double bond to FA's. Electrons are passed to the ETC. Only three desaturases exist in humans: del9 (stearoyl), del6, and del5. (Be sure to know the rules of double bond addition!) |
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Term
| Briefly outline the pathway from Acetyl CoA to a MUFA like Oleate (C18:1w-9) |
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Definition
| Acetyl CoA à Palmitate (ACC and FAS) à Stearate (elongase) à Oleate (SCD) |
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Term
| With a fat-free diet, the w-6 class of FA's is lacking leading to essential FA deficiency. How can this be monitored? |
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Definition
| Watch w-9 polyunsaturates and look for a buildup of 20:3 FA's (like 20:3del5,8,11) |
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Term
| How many C's do eiconosoids have? |
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Definition
| 20. They are synthesized from arachidonic acid (or eiocosapentaenoic acid). |
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Term
| What are the three pathways for eicosanoid synthesis and what does each produce? |
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Definition
| 1) cyclic (prostaglandins, prostacyclins, and thromboxnes), 2) linear (leuotrienes), and 3) cytochrome p450 pathway. All arachidonic acid comes from PL's or DAG, though PL's are major source. |
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