Chapter 20: Lipid Metabolism Flashcards
When triacylglycerols stored in adipocytes are mobilized in times of metabolic need by the action of hormone-sensitive lipase, where are the free fatty acids released?
They are transported into the bloodstream where they bind to serum proteins, mostly serum albumin.
It functions to transport a variety of non-polar substances including hormones and drugs
fatty acids are in high solubility when in complex with albumin
Sentence summary of 𝛃 oxidation. (2 main events)
Fatty acids are progressively degraded by two-carbon units as well as the oxidation of the carbon atom β to the carboxyl group./operates in a repetitive fashion to progressively degrade fatty acids by removing two-carbon units.
Before fatty acids can be oxidized, what reaction must occur?
They must be “primed” for reaction in an ATP-dependent acylation reaction to form fatty acyl-CoA.
Catalyzed by at least 3 acetyl-CoA synthetase
which differ in their chain lenghts
Acyl group of fatty acids are activated by their attachment to coenzyme A
What reaction occurs after the formation of fatty acyl-CoA?
The acyl group is transferred by a carnitine shuttle (leaves CoA in cytosol). The resulting acyl-carnitine is transported into the mitochondria for oxidation and where it is re-esterified to CoA
Carnitine is returned to cytosol.
What reaction occurs after the acyl group is transferred into the mitochondria?
The degradation of fatty acyl-CoA to acetyl-CoA via β oxidation which occurs in 4 reactions.
- Formation of a trans-α, β double bond through dehydrogenation by the flavoenzyme acyl-CoA dehydrogenase (AD).
FADH2 is reoxidized by electron transport chain via ETF - Hydration of the double bond by enoyl-CoA hydratase (EH) to form a 3-L-hydroxyacyl-CoA.
- NAD+ -dependent dehydrogenation of the β -hydroxyacyl-CoA by 3-Lhydroxyacyl-CoA dehydrogenase (HAD) to form the corresponding β -ketoacyl-CoA.
/dehydration to form a β-ketoacyl-CoA
NADH reoxidized by e.t chain - Cα —C β cleavage in a thiolysis reaction with CoA as catalyzed by 𝛃 -ketoacylCoA thiolase (KT; also called just thiolase) to form acetyl-CoA and a new acyl-CoA containing two fewer C atoms than the original one.
/thiolysis by CoA to produce acetyl-CoA and an acyl-CoA shortened by 2 carbons.
The function of fatty acid oxidation is, of course, to generate metabolic energy.
Is fatty acid oxidation endergonic or exergonic?
Each round of β oxidation produces one NADH, one FADH2 , and one acetyl-CoA.
Highly exergonic?
Complete oxidation of a fatty acid yields numerous ATPs.
For example, oxidation of palmitoylCoA (which has a C 16 fatty acyl group) involves seven rounds of β oxidation, yielding 7 FADH2 , 7 NADH, and 8 acetyl-CoA. Oxidation of the 8 acetyl-CoA, in turn, yields 8 GTP, 24 NADH, and 8 FADH2 . Since oxidative phosphorylation of the 31 NADH molecules yields 77.5 ATP and that of the 15 FADH 2 yields 22.5 ATP, subtracting the 2 ATP equivalents required for fatty acyl-CoA formation (Section 20-2A), the oxidation of one palmitate molecule has a net yield of 106 ATP.
What does Each round of β oxidation produce?
Each round of β oxidation produces one NADH, one FADH2 , and one acetyl-CoA.
Oxidation of acetyl-CoA via the citric acid cycle generates an additional FADH 2 and 3 NADH, which are reoxidized through oxidative phosphorylation to form ATP.
Problems presented with he oxidation of unsaturated fatty acids such as linoleum acid?
The double bonds in fatty acids such as linoleic acid pose three problems for the β -oxidation pathway that are solved through the actions of four additional enzymes
The first problem, the presence of a β , γ double bond solved by Enoyl-CoA isomerase, the bond’s conversion to a trans-α, β double bond.
The second problem is A Δ 4 Double Bond Inhibits Enoyl-CoA Hydratase.
Solved by
The third problem is the isomerization of 2,5-dienoyl-CoA by 3,5-dienoyl-CoA Isomerase, is solved by converting the 3,5-dienoyl-CoA to 2,4-dienoyl-CoA, a substrate for 2,4-dienoyl-CoA reductase.
Problem 3:
Isomerization
Problems presented with he oxidation of unsaturated fatty acids such as linoleum acid?
The double bonds in fatty acids such as linoleic acid pose three problems for the β -oxidation pathway that are solved through the actions of four additional enzymes
The first problem, the presence of a β , γ double bond solved by Enoyl-CoA isomerase, the bond’s conversion to a trans-α, β double bond.
The second problem is A Δ 4 Double Bond Inhibits Enoyl-CoA Hydratase.
Solved by
The third problem is the isomerization of 2,5-dienoyl-CoA by 3,5-dienoyl-CoA Isomerase, is solved by converting the 3,5-dienoyl-CoA to 2,4-dienoyl-CoA, a substrate for 2,4-dienoyl-CoA reductase.
Problem 3:
Isomerization
Differences between fatty acids that have even numbers of carbon and those that have an odd number of carbons.
Where do odds occur?
Most fatty acids, for reasons explained in Section 20-4, have even numbers of carbon atoms and are therefore completely converted to acetyl-CoA. Some plants and marine organisms, however, synthesize fatty acids with an odd number of carbon atoms.
Oxidation of Odd-Chain Fatty Acids Yields Propionyl-CoA
The final round of β oxidation of these fatty acids yields propionyl-CoA, which is converted to succinyl-CoA for entry into the citric acid cycle.
Succinyl-CoA Is Not Directly Consumed by the Citric Acid Cycle. How then?
In order for succinyl-CoA to undergo net oxidation by the citric acid cycle, it must first be converted to pyruvate and then to acetyl-CoA
by MethylmalonylCoA mutase that catalyzes the conversion of a metabolite to a citric acid cycle intermediate other than acetyl-CoA.
function of ketone bodies?
Acetyl-CoA may be reversibly converted to ketone bodies in the liver to be used as fuel by other tissues.
It serves as
- fuel for heart, skeletal muscle, other tissues
- fuel for brain (during starvation)
ketogenesis
What is ketosis?
Indeed, in individuals with ketosis, a pathological condition in which acetoacetate is produced faster than it is metabolized (a symptom of diabetes; Section 22-4B), the breath has the characteristic sweet smell of acetone.
difference between fatty acid biosynthesis and degradation
Biosynthesis similar to reversal od degradation
Biosynthesis occurs in the cytoplasm. Degradation occurs in the mitochondria.
Biosynthesis acyl-ACP (only Carry proteins)anchors to ACP, Degradation acyl-CoA anchors to CoA
in C2 steps, biosynthesis (Molonyl,-CoA), Degradation (acetyl-CoA)
Biosynthesis, only NADPH both redox rxns, Degradation FAD and NAD+
Biosynthesis D-b-hydroxyacyl-ACP instead of L-b-hydroxyacyl-CoA
Biosynthesis- all activities on one complex
Sentence summary of F.A. Biosynthesis
Fatty acid biosynthesis occurs through condensation of C 2 units, the reverse of the β -oxidation process.
