lipid synthesis: palmitate modification Flashcards
list 5 things we can do with palmitate
elongate it, desaturate it, make eicosanoids, make TAGs, make membrane phospholipids
list the 4 basic steps of FA elongation
condensation, reduction, dehydration, reduction
what do you get after elongating palmitate once
stearate (18:0)
where does FA elongation occur in the cell (2)
smooth ER and mitochondria
what two things serve as precursors for desaturation
palmitate and stearate
name the two most common MUFAs
palmitoleate and oleate
what is the shorthand of palmitoleate
16:1(Δ9)
what is the shorthand of oleate
18:1(Δ9)
what enzyme family is involved in adding double bonds to FAs
desaturases
name the process of converting palmitate to palmitoleate
desaturation
name the processes of converting palmitate to oleate
elongation (=stearate) followed by desaturation
describe the process of adding double bonds via desaturase
both FA-CoA and NADPH lose 2 electrons, and molecular oxygen receives them and is reduced to water (water acts like an electron acceptor so the double bond can be made)
which end of the FA chain are double bonds added to via desaturases
the methyl end
T or F: mammals do not have desaturases to add double bonds to the methyl end
true
because mammals don’t have desaturases, which 2 important molecules are we unable to produce
linoleic acid and a-linolenic acid (the omegas)
what is the shorthand name for linoleic acid?
18:2 (Δ9,12)
what is the shorthand name for linolenic acid?
18:3 (Δ9,12, 15)
T or F: plants do not have desaturases
false; they do
how do mammals obtain linoleic and linolenic acid?
from the diet
sources of linoleic acid?
vegetable oils
sources of linolenic acid?
green leafy veggies, flax and chia seeds, canola and soybean oils
how is linoleate produced from oleate
desaturation
how is linolenate produced from linoleate
desaturation
list the omega 6 derivatives of linoleate (3)
y-linolenate, eicosatrienoate, and arachidonate
list the omega 3 derivatives of linoleate (3)
a-linolenate, EPA, DHA
T or F: we directly ingest the omegas
false; we indirectly ingest them
describe how mammals obtain omegas via indirect ingestion
we must ingest linoleic and a-linolenic acid, and then those can be further desaturated and elongated to make PUFAs
which part of the brain heavily relies on PUFAs
grey matter membranes
list some benefits of FAs to grey matter membranes of the brain
enhances synaptic plasticity and memory, inhibits the production of neurotoxic cytokines, stimulates neurite outgrowth, increases cognition for people with alzheimer’s, lowers heart disease, lowered inflammatory response
list two groups of people that have been found to have low PUFAs in the blood
people with schizophrenia/depression, children with autism spectrum disorders
what are the three eicosanoids derived from
arachidonic acid
T or F: several hormones stimulate eicosanoid synthesis
true
where is arachidonic acid in regards to phospholipids
it serves as the FA tails
describe how eicosanoid synthesis is triggered while arachidonic acid is serving as the FA tail in phospholipids
hormones will trigger A2 phospholipases to cleave a membrane phospholipid, freeing arachidonic acid
what frees arachidonic acid from phospholipids
A2 phospholipases
after arachidonic acid is freed from phospholipids during eicosanoid synthesis, what occurs?
enzymes will convert it to an initial prostaglandin (PGH2) in a two step process
which enzyme converts freed arachidonic acid to PGH2? what is a special characteristic of this enzyme?
the conversion occurs via a multi-functional enzyme called cyclooxygenase
describe how cyclooxygenase (COX) is multifunctional. What types of activity does it have?
cyclooxygenase activity: COX introduces 2 oxygens to form an intermediate ringed peroxide
peroxidase activity: COX reduces one peroxide to alcohol to form PGH2
how many forms of the COX enzyme do mammals have
2
what two forms of the COX enzyme do mammals have
COX1 and COX2
which eicosanoid’s synthesis is blocked during the use of asprin?
prostaglandin
describe how aspirin blocks prostaglandin synthesis
it acetylates a serine residue in the active site to inhibit COX2, which reduces pain and inflammation. It also inhibits COX1, leading to some side effects
describe how aspirin may cause side effects
it inhibits COX2 (blocks prostaglandin synthesis), but also inhibits COX1 = side effects. COX1-synthesized prostaglandins regulate mucus levels in the stomach, so aspirin can cause stomach lining irritation
what enzyme generates thromboxanes from PGH2
thromboxane synthase
where is thromboxane synthase located in the body? link this location to the function of thromboxanes
thromboxanes assist in platelet aggregation + blood vessel constriction. Thromboxane synthase is located in platelets
what is the effect of aspirin reducing thromboxane production
low doses of aspirin reduces the probability of heart attack/stroke by reducing thromboxane synthesis
what happens to made FAs during periods of growth (where do they go)
they’re incorporated into the PM as phospholipids
what happens to made FAs during periods of no growth (where do they go)
they’re incorporated into TAGs for energy storage
what two precursors are needed for TAG synthesis
glycerol-3-phosphate and fatty acyl-CoA
how is glycerol-3-phosphate made (to be used in TAG synthesis) (2 ways)
formed from a glycolysis intermediate, or from glycerol in the liver/kidney in an ATP-depended reaction by glycerol kinase
how is fatty acyl-CoA made (to be used in TAG synthesis)
made by acyl-CoA synthetase enzymes (this costs ATP)
write out the reaction of fatty acyl-CoA production
fatty acid + CoA + ATP –> fatty acyl-CoA + AMP + 2Pi
how many ATP equivalents does it take to add a CoA onto a FA (in TAG synthesis)
2 ATP equivalents
once the precursors of TAG synthesis have been made (glycerol-3-phosphate and fatty acyl-CoA), what is the first step/product of TAG synthesis
phosphatidic acid aka diacylglycerol-3-phosphate
how is phosphatidic acid made during TAG synthesis
two free OH groups on glycerol-3-phosphate are acylated via acyl transferases
what enzyme acylates the two free OH groups on glycerol-3-phosphate to make phosphatidic acid (in TAG synthesis)
acyl transferase
how much ATP does it take to acylate the 2 free OH groups of glycerol-3-P to make phosphatidic acid
2 ATP equivalent (per acyl chain)
once phosphatidic acid is made (during TAG synthesis), what is the next step + what enzyme does the step
it’s hydrolyzed by phosphatidic acid phosphatase to make 1,2-diacylglycerol
once 1,2-diacylglycerol is made during TAG synthesis, what is the next step
the final acyl group is added to generate the triacylglycerol
what is the cost of adding the final acyl group to 1,2-diacylglycerol to form TAG
2 ATP to add, but remember it also costs 2 ATP to FORM this fatty acyl-CoA
what is the final ATP cost of TAG synthesis
12 ATP
how might insulin regulate the TAG synthesis pathway
insulin is present after we eat, so we don’t want to be making fats but storing them. insulin promotes acetyl-CoA formation and the eventual formation of TAGs. This is because we want to store what we have eaten, so we store the TAGs that get made
describe TAG synthesis regulation for a diabetic
a diabetic person wouldn’t be getting enough acetyl-CoA, so we wouldn’t want TAGs to be made because TAGs are for storage. Instead, acetyl-CoA will be used to make ketone bodies instead of making TAGs
where in the body does the TAG cycle take place (3)
adipose tissue, blood, and liver
what percentage of free FAs released from TAG breakdown are used for fuel
25%
what percentage of free FAs released from TAG breakdown are used to regenerate TAGs
75%
list the basic steps of the TAG cycle, staring in the adipose tissue
from the adipose tissue, starvation causes it to release free FAs into the blood, and some of these will be used for fuel. Most free FAs go back to the liver to be re-packaged into TAGs, go back to the blood, then back to adipose tissue
why does the body use the “futile” TAG cycle
the cycle keeps some free FAs in the blood for immediate breakdown in a sudden energy need
what molecule is required in high amounts for the TAG cycle to occur? where is this molecule located (2)
glycerol-3-phosphate is needed in adipocytes and hepatocytes
list 3 ways to generate glycerol-3-phosphate
from glucose (via glycolysis), from glycerol (after phosphorylation by glycerol-kinase), and from pyruvate (via glyceroneogenesis)
for the TAG cycle specifically, where do we get the glycerol-3-phosphate from
pyruvate (glyceroneogenesis)
describe glycerol-3-phosphate production from glucose
glucose undergoes some steps of glycolysis but stops when DHAP is produced. From here, glycerol-3-phosphate dehydrogenase and NADH are used to make glycerol-3-phosphate
describe glycerol-3-phosphate production from pyruvate (when fasting)
pyruvate undergoes glyceroneogenesis to produce DHAP. From here, glycerol-3-phosphate dehydrogenase and NADH are used to make glycerol-3-phosphate
which enzyme controls TAG cycle flux
PEP carboxykinase
what reaction does PEP carboxykinase mediate
pyruvate –> PEP
where is PEP carboxykinase located in the body
adipose tissue and the liver
what does it mean for the TAG cycle to have PEP carboxykinase in both the adipose tissue and the liver
PEP carboxykinase is able to create lots of flux via the back and forth of fatty acids between adipose and liver
describe what occurs when PEP carboxykinase is expressed in the liver
lots of glyceroneogenesis, which makes more TAGs. The TAGs are exported back to adipose tissue, and this promotes much flux through the TAG cycle. This is important during starvation so you get that 25% of free FAs to the muscle
describe what occurs when PEP carboxykinase is expressed in adipose tissue
increased glyceroneogenesis makes more TAGs which cycle WITHIN adipose tissue = not much flux through the cycle. This is useful when there is other fuel around (ie glucose)
which steroid hormone regulates levels of PEP carboxykinase in the liver/adipose
cortisol
describe how cortisol affects PEP carboxykinase levels
it causes an increase in PEP carboxykinase levels in the liver, and a decrease in adipose tissue = maximum TAG cycle flux
what do high levels of TAG cycle flux cause in the body? (4)
promotes insulin resistance –> type II diabetes, increases blood pressure, increases risk of liver disease and atherosclerosis, overexpression of PEP-related genes promotes obesity
where do we WANT PEP carboxykinase to be active
adipose tissue only (low flux)
T or F: A group of drugs used to treat type II diabetes promotes synthesis of PEP carboxykinase in adipose tissue only
true
T or F: PEP carboxykinase activity in adipose tissues ONLY lowers the amount of free FAs in the blood
true
T or F: PEP carboxykinase activity in adipose tissues ONLY decreases a person’s insulin sensitivity
false; it increases a person’s insulin sensitivity
describe the steps of phospholipid synthesis starting with phosphatidic acid
make phosphatidic acid and then DAG by cleaving off a P. Add an initial headgroup to the backbone through a phosphodiester linkage. When DAG, P and headgroup all come together, 2 waters will be released. Modify the headgroup (if needed)
what type of bond links the head group to DAG (during phospholipid synthesis)
phosphodiester linkage
describe how to add a head group during phospholipid synthesis
form a phosphodiester bond with the OH on the 3C of DAG and an OH on the head group. One of these alcohols first needs to be activated
in phospholipid synthesis, what activates the OH to form the phosphodiester bond that attaches the head group
cytidine diphosphate (CDP)
in phospholipid synthesis, what does the other OH do after the first was activated by CDP
the second OH completes nucleophilic attack to displace cytidine monophosphate (CMP)
in bacteria phospholipid synthesis, which OH does CDP attach to; the one on DAG or the one on the head group
the one on DAG
in eukaryotic phospholipid synthesis, which OH does CDP attach to; the one on DAG or the one on the head group
CDP can attach to both
in phospholipid synthesis in BACTERIA, what is the head group
serine
in phospholipid synthesis in YEAST, what is the head group
serine or inositol
in phospholipid synthesis in MAMMALS, what is the head group
choline or ethanolamine
list 3 potential head group modifications of the yeast serine headgroup (in phospholipid synthesis)
-CDP-DAG condenses with serine to make phosphatidylserine
- decarboxylation of PS to from phosphatidylethanolamine
- adding 3 methyl groups onto the PE amine to make phosphatidylcholine
where are lipids made
smooth ER
after lipids are made in the smooth ER, where are they transported to
to the golgi
how are synthesized lipids transported from the smooth ER to the golgi
via vesicles
after arriving to the golgi after synthesis, where do lipids go?
they move to membranes via vesicles in specific proportions
