21: lipid synthesis Flashcards
(43 cards)
Do you know how to name fatty acids? and recognize structure?
count from the carboxyl carbon, unsaturations denoted with ∆. for common naming, saturated ate -ate and unsaturated are -oleic acid, eg palmitate and palmitoleic acid remember most fatty acids are even numbers.
Eicosanoids structure and function
20C polyunsaturated FA with derivatization
signaling, such as PGEs and thromboxanes
triacylglycerols structure and function
glycerol molecule with three fatty acids
energy storage
glycerophospholipids structure and function
glycerol molecule with two FA and a phosphate linked head group, can have a few different head group that define identity
membrane components
cholesterol structure and function
27C, multi cyclic, derived from isoprene units (from mevalonate)
membrane component and precursor for steroid hormones
Describe the steps of biosynthesis of FAs
occurs in cytoplasm
- synthesize malonyl-CoA by AcetylCoA carboxylase ACC
- long C chains of FA assembled in 4 step sequence by FA synthase
- acetate precursor shuttled into cytoplasm as citrate
- desaturation requires mixed-function oxidase activity
mechanism of ACC acetyl-coA carboxylase
21 Pt 1 slide 5
uses biotin carboxylase and ATP to carry CO2 (from HCO3-). then transcarboxylase combines acetyl-coA and CO2 to make malonyl-coA
1st, committed step in FA synthesis (highly regulated)
mechanism of FAS fatty acid synthase
21 pt1 slide 6
multi enzyme complex has long and short arm. Malonyl and acetyl precursors are activated by a thioester. decarboxylation condensation occurs and the acetyl group is added to the malonyl. reduction occurs using NADPH and then dehydration and then another reduction from NADPH. Then another malonyl is added and the cycle repeats.
Condensation, Reduction, Dehydration, Reduction
FAS involves getting rid of CO2, is this wasteful since we just worked so hard to incorporate CO2??
Nah. condensation of an acetyl group to and acyl chain is an endergonic process, so the CO2 is needed as a good leaving group to make the process favorable. CO2 loss during condensation results in an exergonic process
what is acyl carrier protein and how does it work?
ACP has a 4’ phosphopantethiene group which acts as a flexible arm. it has a thiol group which esterifies to malonyl groups and can transfer the growing product to the next enzyme active site.
how many carbons is palmitate?
16
what is required to make one molecule of palmitate? stoichiometry practice
ACC (7 cycles): needs 7 acetyl-coA + 7 CO2 + 7 ATP to produce 7 malonyl CoA
FAS (7 cycles): needs 1 acetyl-coA + 7 malonyl-coA + 14 NADPH + 14 H+ to produce one palmitate
NET: 8 acetyl-coA + 7 ATP + 14 NADPH + 14 H+ –> palmitate + 8 CoA + 7ADP + 7 Pi + 14 NADp + 6H2O
what are some homologues to FAS in other organisms
bacteria, plants: seven activities in seven separate polypeptides
yeast: seven activities in two separate peptides
vertebrates: seven activities in one large polypeptide
where in the cell does FA synthesis take place? plant and animal
animal cell: FA synthesis in cytosol, elongation and desaturation and modifications in ER and mitochondria (elongation)
plant cell: FA synthesis in chloroplast, elongation and desaturation and modifications in ER and mitochondria (elongation)
where does the acetyl-coA for FA synthesis come from?
nearly all from mitochondrial oxidation of pyruvate and amino acid catabolism. mitochondrial membrane is impermeable to acetyl-coA, so it must be made into citrate and go through citrate transporter to get out
how is FA synthesis regulated?
ACC is rate limiting step. palmitate (the ultimate product) inhibits ACC and citrate is and allosteric activator. ACC can also by phosphorylated. glucagon and epinephrine inhibit ACC. It is important to keep tight control bc it is so energetically costly
what happens if a FA longer than 16 C is needed?
fatty elongation system is in the smooth ER and mitochondria.
what happens if a FA needs a double bond?
needs mixed function oxidases, meaning 2 substrates are oxidized. desaturases have substrate specificity so that double bonds cannot be formed anywhere, some FAs have to be ingested bc the desaturases don’t make them. Desaturations require O2 and NADPH
21 pt 1 slide 17
how are Eicosanoids synthesized?
a phospholipid containing arachidonate is modified by cyclooxygenase (COX). the products are prostaglandins and thromboxanes, which are responsible for controlling fever, pain, blood clotting, and other responses.
why is COX a drug target? what are some ways it is targeted?
COX is responsible for producing prostaglandins and thromboxanes which are pain, fever, clotting, etc signals. less thromboxanes means less platelets aggregation and clotting. this prevent heart attacks. Aspirin has an acetyl group that acetylates a Ser residue on COX, inactivating it.
COX 1 vs COX 2
COX 1: synthesis of PGEs that regulate secretion of gastric mucin
COX 2: synthesis of PGEs that mediate inflammation, pain, and fever
inhibitors of COX 2 will avoid bothering your stomach!
what are leukotrienes and how are they synthesized?
inflammatory molecules responsible for causing contractions in smooth muscles linking bronchioles. basically a special type of Eicosanoids. They originate from arachidonate and require mixed function oxidases to make
compare TAGs and glycerophospholipids
Triacylglycerols have three FA chains, and function to store energy. glycerophospholipids have two FA chains and one phosphate attachment and function in membranes. Both are made from the same precursor, phosphatidic acid (branch point)
how is phosphatidic acid (and then glycerolphospholipids and triacylglycerols) synthesized?
21 pt 2 slide 3
DHAP or glycerol goes through acyl transferase twice. Uses ATP and CoA-SH and acyl group
Phosphatidic acid can then make glycerophospholipids by CTP reaction or it can make TAGs by being hydrolyzed and acylated
