Term
| What are some pathways that produce NADPH for biosynthetic reactions? |
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Definition
1) Pentose Phosphate Pathway
2) Citrate/Pyruvate Cycle
3) Isocitrate Cycle |
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Term
| How does the citrate-pyruvate cycle produce NADPH? |
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Definition
Citrate produced in the TCA cycle and then converted to OOA.
OOA is then converted to malate
Malate is converted by malic enzyme to form pyruvate and produce NADPH |
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Term
| How does the isocitrate cycle produce NADPH? |
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Definition
| Citrate (from the TCA) is converted to isocitrate in the cytosol and isocitrate dehydrogenase converts it to alpha-ketoglutarate and producing NADPH |
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Term
| What is the role of citrate in fatty acid synthesis? |
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Definition
Citrate is used to transport Acetyl CoA from the mitochondria to the cytosol (Acetyl CoA can't cross the membrane)
Acetyl CoA and OOA form citrate in the TCA cycle in the mitochondria and then citrate is transported to the cytosol.
ATP-citrate lyase cleaves citrate back into OOA and Acetyl CoA which is essential in FA synthesis. |
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Term
| What is the rate controlling step in FA synthesis? |
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Definition
The conversion of Acetyl CoA to Malonyl CoA by acetyl CoA carboxylase
This enzyme requires biotin as a co-factor |
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Term
| Explain the allosteric regulation of acetyl CoA carboxylase |
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Definition
The protomer form of acetly CoA carboxylase is inactive while the polymer form is the active form
Citrate activates the polymerization
Malonyl CoA inhibits the polymerization (product inhibition)
Palmityl CoA (which can come from diet) inhibits the polymerization |
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Term
| How does the energy charge of the cell affect acetly CoA carboxylase? |
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Definition
ATP inhibits AMPKK
decreased AMPKK leads to decreased AMPK
decreased AMPK leads to decreased phosphorylation of Acetyl CoA carboxylase (the inactive form)
so ATP increases levels of the active form of acetyl CoA carboxylase which increases FA synthesis
AMP has the opposite overall effect as it activates AMPKK |
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Term
| How does insulin regulate acetyl CoA carboxylase? |
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Definition
Insulin activates protein phosphatase
Protein phosphatase dephosphorylates the inactive form of acetyl CoA carboxylase to the active form
Insulin also activates the conversion of AMPK to its inactive form which increases the level of activated acetyl CoA carboxylase
Thus insulin increases FA synthesis |
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Term
| How does glucagon affect acetyl CoA carboxylase? |
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Definition
Glucagon increases cAMP levels
cAMP activates cAMP-dependent protein kinase
cAMP-dependent protein kinase activates AMPKK
AMPKK activates AMPK
AMPK inactivates acetyl CoA carboxylase
Glucagon decreases FA synthesis
Remember glucagon and isulin have opposing effects in metabolism pathways |
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Term
| How does Acyl CoA affect acetyl CoA carboxylase? |
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Definition
It participates in product inhibition
It activates AMPKK
AMPKK activates AMPK
AMPK inactivates acetyl CoA carboxylase |
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Term
| Explain the priming phase of FA synthesis |
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Definition
The fatty acid synthase complex contains ACP-SH and CYS-SH. ACP is acyl carrier protein which resembles CoA
Acetyl CoA is the primer and the first two C's (the ketone group) react with ACP-SH and kick off the H.
Then the ketone group from Acetyl CoA switches from the ACP to the CYS-S. |
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Term
| Explain the linkage and elongation phase of FA synthesis |
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Definition
Malonyl CoA (which was produced by acetyl CoA carboxylase) adds a ketone group with a COO- attached to ACP-S.
The ketone group (from the Acetyl CoA primer) on CYS-S then attacks the ketone group on ACP-S and kicks of C02
This has elongated the chain on ACP by 2 C's (another ketone group) |
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Term
| Explain the reducing phase of FA synthesis |
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Definition
The ketone group at the end of the chain attached to ACP-S is reduced to an alcohol group
Then H20 is kicked off and a double bond is formed between the second to last C and the third to last C
NADPH then reduces that double bond to a single bond
The cycle can then start over |
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Term
| Explain the basics of palmitate synthesis |
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Definition
1) priming phase
2) linkage and elongation phase
3) reducing phase
4) cycle repeats 6 more times but now with malonyl CoA serving as the "primer"
Each round of the cycle adds 2 C's to the FA chain (remember the original C's from acetyl CoA stay at the end of the chain)
Once palmitate is finally synthesized and attached to ACP-S, water comes in and binds with palmitate to release it and form the free FA |
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Term
| What are the different desaturases and what are their roles in FA synthesis? |
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Definition
| delta 4,5,6, and 9 are the different desaturases. They add double bonds to their respective C's |
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Term
| How is arachidonate synthesized? |
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Definition
It is synthesized from lineloate
delta 6 desaturase adds a double bond
elongase adds 2 C's to the chain near the beginning
delta 5 desaturase adds the final double bond |
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Term
| How can FA chains be elongated? |
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Definition
Malonyl CoA can add 2 C's to an Acyl-CoA group
The enzymes used are 3-ketoacyl-CoA synthase, 3-ketoacyl-CoA reductase, 3-hydroxyacyl-CoA dehydrase, and 2-trans-enoyl-CoA reductase |
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Term
| How are trigylcerides synthesized? |
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Definition
DAP produced from glycolysis is reduced to from glycerol 3-phosphate
FA chains attached to CoA are attached to C1 and C2 of glycerol 3-phosphate to form phosphatidic acid
The phosphate group on C3 leaves to form 1,2 diacyl glycerol
Another FA chain attached to CoA is attached to C3 to form the triglyceride |
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Term
| How is triglyceride synthesis regulated? |
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Definition
| It is regulated at the gene expression level by controlling enzyme synthesis |
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Term
| How does alcohol affect the liver? |
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Definition
The conversion of alcohol (ethanol) to acetate produces NADH
Increased NADH levels inhibit the use of Acetyl CoA in the TCA cycle
Acetyl CoA then is used in FA synthesis which will lead to triglyceride synthesis causing a fatty liver |
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Term
| Explain the clinical spectrum of fatty liver |
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Definition
Normal liver is converted to fatty liver (steatosis) - this step is reversible and there are few clinical signs
Fatty liver to steatohepatitis is the critical transition. This is the 2nd "hit" and worsened by chronic alcohol and obesity.
Steatohepatitis is the precursor to cirrhosis and it is also susceptible other liver injuries |
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Term
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Definition
Fatty infiltration of the liver
Increased synthesis of fat
Enlarged fat cells
Choke off nutrient and O2 supply to liver cells
Engorged fat cells burst and die
Scar tissues
Advanced stages are not reversible
Destruction of vital tissues regardless of diet
50% chance of death within 4 years |
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Term
| How does brain adipose tissue generate heat? |
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Definition
Thermogenin is a channel that disrupts the proton gradient in the ETC
It allows H+ to flow back into the mito. matrix instead of going through the ATP Synthase and the energy is released as heat. |
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