Textbook notes corresponding to weekly reading guide of Biochemistry course (code BIOSCI98) at University of California, Irvine. Comes with reading guide and color-coded notes. Week 10.
Wk10RG
Monday, March 11, 2019 11:43 PM
B-oxidation of Lipids
• B-oxidation: fatty acids are converted into acetyl-CoA in 4-step process.
• Dietary fats are absorbed in the small intestine. In response to fats ingested. Fig. 17-1, pg. 650
• In small intestine, bile salts turn fat into micelles of bile salts+triacylglyercol -> intestinal lipases degrade triacylglycerol -> degraded products diffu
intestinal surface, then reconvert into triacylglycerol and packaged w/ cholesterol/apolipoproteins into chylomicrons. -> while in the bloodstream,
lipase (activated by apoC-II) converts triacylglycerol into fatty acids/glycerol.
• In muscle, fatty acids are oxidized for energy.
Week 10 • In adipose, fatty acids are re-esterified (back to triacylglycerols) for storage.
• Hormones trigger mobilization of stored triacylglycerols. Only happens in response to glucose blood levels.
• Hormones signal -> Stored triacylglycerols are mobilized (brought out of storage) and transported to tissues in which fatty acids can be oxidized.
○ Condition: cell in need of metabolic energy, Location: adipose tissue -> muscle tissue
• Low [blood glucose], or flight/fight response -> signals Glucagon -> adenyl cyclase in adipocyte plasma membrane -> produces cAMP, triggers p
phosphorylation of hormone-sensitive lipases/perilipin (and of acetyl-CoA carboxylase)-> lipases degrade triacylglycerol into fatty acids and glyc
pg. 652
• Fatty acids leave lipid droplet and travel in the bloodstream (bound to serum albumin) -> enter myocyte (specific fatty acid transporter); are oxidiz
and ATP -> energy used for muscle contraction.
• Fatty acids are activated and transported into mitochondria.
• Carnitine shuttle: 3 enzymatic rxns that allow large fatty acids (+14 carbon-FFAs) to enter mitochondrial matrix.
○ Why: fatty acid oxidation, Where: rxns start in outer mitochondrial membrane.
○ (1) esterification of CoA to fatty acid-> fatty acyl-CoA, (2) trans-esterification to carnitine, followed by passive transport into matrix, and (3)
esterification back to CoA. Fig. 17-6, pg. 654
○ "Passive transport" is aided by carnitine acyltransferase 1 and inner-membrane integral transporter.
○ Carnitine acyltransferase is inhibited by malonyl-CoA. INC in malonyl-CoA -> fatty acids into the mitochondria, DEC in fatty acid oxidation.
• The B-oxidation of saturated fatty acids has 4 basic steps.
1. Dehydrogenation of fatty acyl-CoA -> trans-delta2-enoyl-CoA, 7 FADH2 -> 10.5 ATP
a. Catalyzed by acyl-CoA dehydrogenase. New double bond is trans, not cis.
b. Flavoproteins steal fatty acyl-CoA electrons, donating them to ETF -> FAD for respiratory chain.
2. Water added to trans-delta2-enoyl-CoA -> L isomer B/3-hydroxyacyl-CoA.
a. Catalyzed by enol-CoA hydratase.
b. H2O adds across the a-B double bond (why its called beta-oxidation).
3. Dehydrogenation of L-B-hydroxyacyl-CoA -> B-ketoacyl-CoA, 7 NADH, 17.5 ATP
a. Catalyzed by B-hydroxyacyl-CoA dehydrogenase.
b. NADH formed donates its e- to NADH dehydrogenase, e- carrier in respiratory chain.
4. Thiolysis: Splits off carboxyl terminal of B-ketoacyl-CoA w/ help of CoA-SH. -> acCoA+Acyl group!
a. Catalyzed by thiolase.
• QUESTION When (16C) palmitate is oxidized, an acetyl-residue is removed in the form of acetyl-CoA (requires 2Cs) from carboxyl end of chain
acetyl-CoA molecules are made after all of palmitate is oxidized?
○ 8 acetyl-CoA
• Purpose of B-oxidation: to destabilize and break stable methylene bonds in fatty acids. Helps begin fatty acid oxidation.
• B-oxidation steps are repeated to yield acetyl-CoA and ATP.
• Oxidation of unsaturated fatty acids requires 2 additional reactions (*).
• Unsaturated fatty acids have one or more double bonds in the cis configuration; cannot be acted upon by enol-CoA hydratase.
• For monounsaturated fatty acids: isomerase
○ Oleate -> Oleoyl-CoA. Carnitine shuttle into mitochondria. Oxidation x3 -> 3 acetyl-CoA and cis-delta3-dodecenoyl-CoA.
○ *Isomerization of cis-delta3-dodecenoyl-CoA -> trans-enoyl-CoA.
• Catalyzed by enoyl-CoA isomerase.
○ ** trans-enoyl-CoA -> trans-delta3-dodecenoyl-CoA (L-3-hydroxyacyl-CoA).
• Can NOW be catalyzed by enoyl-CoA hydratase.
○ Intermediate acted upon by remaining enzymes of B-oxidation.
• For polyunsaturated fatty acids: reductase
• Linoleoyl-CoA. Oxidation x3 -> 3 acetyl-CoA and cis-delta3, cis-delta6
○ Coenzyme A ester is in wrong configuration. Cannot be acted upon by B-oxidation enzymes.
○ 2,4-dienoyl-CoA reductase AND enoyl-CoA isomerase -> 6 acetyl-CoA.
○ Total: 9 acetyl-CoA molecules! Produces 1 more than saturated fatty acids, and more than quadruple during pyruvate oxidation.
• B-oxidation and TCA: first 3 steps are similar to last 3 steps of TCA (starting w/ succinate dehydrogenase).
• Complete oxidation of odd-number of fatty acids requires 3 extra reactions.
• Same pathway, however the substrate for the last pass of B-oxidation sequence is a 5C-fatty acid chain (instead of 4C). Once oxidized/cleaved,
acetyl-CoA + propionyl-CoA.
Acetyl group is transferred from the Cys SH- group of KS enzyme -> acetyl+aceto- ○ Propionyl-CoA -> D-methylmalonyl-CoA -> L-methylmalonyl-CoA -> Succinyl-CoA! Can enter TCA.
group attaches to the -SH of ACP • Fatty acid oxidation is tightly regulated.
• Transferring of fatty acyl groups from cytosol to mitochondrial matrix is important point of regulation!
The benefits of buying summaries with Stuvia:
Guaranteed quality through customer reviews
Stuvia customers have reviewed more than 700,000 summaries. This how you know that you are buying the best documents.
Quick and easy check-out
You can quickly pay through credit card or Stuvia-credit for the summaries. There is no membership needed.
Focus on what matters
Your fellow students write the study notes themselves, which is why the documents are always reliable and up-to-date. This ensures you quickly get to the core!
Frequently asked questions
What do I get when I buy this document?
You get a PDF, available immediately after your purchase. The purchased document is accessible anytime, anywhere and indefinitely through your profile.
Satisfaction guarantee: how does it work?
Our satisfaction guarantee ensures that you always find a study document that suits you well. You fill out a form, and our customer service team takes care of the rest.
Who am I buying these notes from?
Stuvia is a marketplace, so you are not buying this document from us, but from seller PrinceAlixD. Stuvia facilitates payment to the seller.
Will I be stuck with a subscription?
No, you only buy these notes for $2.99. You're not tied to anything after your purchase.
