Lipid Metabolism Overview
Terms in this set (42)
What is a major co-substrate for lipid metabolism
Structure of Acetyl CoA
Where does fatty acid synthesis take place?
Occurs in the cytoplasm
How is Acetyl CoA used in fatty acid synthesis?
Produces malonyl-CoA and Acetyl-ACP for chain elongation
How does Acetyl CoA get into the cytoplasm?
It is synthesized in the mitochondria from pyruvate, and then used to produce citrate. Citrate is then transported into cytoplasm and cleaved with energy to produce it.
Protein that transports Citrate out of mitochondria?
Tricarboxylic Acid Transporter
Describe Acetyl CoA from citrate reaction
reverse reaction of citrate synthesis (uses ATP-Citrate Lysase) and requires energy to make it favorable
What are the three coenzymes of Fatty Acid Synthesis
Coenzyme A, Acyl Carrier Protein (ACP), Biotin (Bi)
Acyl Carrier Protein (ACP)
Difference between Coenzyme A and ACP
ACP is attached to a serine residue on the protein, Coenzyme A is attached to ADP
Activated form of Biotin prosthetic group?
The NH on the side of the ring, the H is removed and replaced with a OCOOH group
Steps of Initiation stage of Fatty Acid Synthesis
Acetyl CoA forms Acetyl-ACP and malonyl-ACP, which then are used together to create acetoacetyl-ACP
Steps of Elongation State of fatty acid synthesis
Acyl-ACP and malonyl-ACP are used to add on 2 more carbons, making a new acyl-ACP, can continuously repeat
The CoA bond is broken by aceytyl CoA:ACP transacetylase and replaced by ACP, both bonds are thioester.
Addition of a carboxyl group to Acetyl CoA (on the methyl group) which is catalyzed by Acetyl CoA carboxylase and metabolically irreversible. Uses ATP. Biotin transfers the carboxyl group.
A simple acyl transfer from Coenzyme A to ACP on malonyl-CoA
3-ketoacyl ACP synthase uses acetyl-ACP and malonyl-ACP. Malonyl-ACP undergoes a decarboxylation. HS-ACP is released from acetyl-ACP.
Math of Acetoacetyl-ACP synthesis
What drives Acetoacetyl-ACP synthesis
The decarboxylation of Malonyl-ACP
Smallest version of growing fatty acid chain (or 3-ketoacyl molecule)
Three steps of fatty acid chain elongation
What does the first reduction step due during fatty acid synthesis
The 3-keto is reduced to an alcohol at that carbon, a reductase, uses NADPH. D-3-hydroxyacyl ACP
What does the dehydration reaction due during fatty acid synthesis?
Dehydration produces a double bond between beta and alpha carbon, produces water, dehydratase. Enoyl-ACP is produced
What does the second reduction reaction due during fatty acid synthesis?
Another reduction down to an acyl group, uses an NADPH, reductase. Creates an Acyl-ACP
The re-creation of a 3-keto is down through what?
The reaction between the new Acyl-ACP and malonyl CoA (last step initiation) to add on 2 more carbons to the chain
How is malonyl-ACP used in chain elongation?
Adds 2 carbon to each chain of fatty acid tail of previous acyl-ACP, with the loss of a carbon dioxide
How does the fatty acid chain become unsaturated?
Desaturase enzymes, that uses NADH and produces water, after chain synthesis
What is the primary source of stored lipids as energy?
Site of Beta-Oxidation
How do you produce acetyl-CoA from fatty acids?
1) Activation of fatty acids in 3 sequential reactions
2) Degradation or Cleavage to 2-Carbon Fragments
What are the 3 reactions of activation of fatty acids?
What is the reaction of fatty acid degradation or cleavage to 2-Carbon fragments?
Thiolysis, sulfhydryl group of HS-Coenzyme A acts as a nucleophille to attack carbonyl carbon of 3-ketoacyl CoA of fatty acid chain. Produces Acetyl CoA and fatty acid chain reduced by 2-carbons
Acetyl CoA Paths
1) Enter TCA cycle for complete oxidation
2)Use as an intermediate for other pathways
Steps in Beta Oxidation Pathway
1) Acyl CoA reacts with FADH to produce an trans-delta2-Enoyl CoA. 2) Water added to produce L-3-hydroxyacyl CoA. 3) NADH produced to form a 3-ketoacyl CoA. 4) HS-CoA is added to produce Acetyl CoA and an acyl-CoA shortened by 2 carbons
Oxidation of Fatty Acyl CoA by Acyl-CoA dehydrogenase
Occurs through electron passing. Electron passes from acyl CoA to FAD, FAD in ETF complex, to Fe-S, to Q producing QH2
Electron flow of first oxidation reaction
1) Electron removed from fatty acyl CoA by FAD+ reduction in the enzyme acyl-CoA dehydrogenase. 2) Passed from FADH2 to FAD+ in a protein coenzyme, electron transferring flavoprotein (ETF). 3) Passed from FADH2 in ETF to Fe-S cluster in ETF. 4) passed a reduced Fe-S cluster in enzyme ETF:ubiquinone.
Thiolysis of 3-Keto Acyl CoA by Thiolase
Cleaved between CH2 and C=O. Forms Acetyl-CoA and a fatty acid chain with 2 less carbons, which can continue through beta-oxidation