Fats Flashcards
What is the Greek word for lipid?
lipos (fat)
What is a lipid?
biomolecules that partition into organic as opposed to aqueous solution
What are lipids involved in?
- energy storage
- cell structure
- signal transduction
- intracellular transport
What falls under the lipids category?
- dietary oils and fats
- cholesterol
- hormones
- inflammatory mediators
- vitamins
How many genes are in lipid metabolism alone?
1116 genes
How many estimated genes involved in lipid binding proteins are there?
1000 genes
What are lipids major importance for?
cell function and structure
How many families of lipids are there?
8
How many lipid families does the human plasma contain?
6
How many structurally different lipids are in the human plasma?
588
What does the double bond introduce into the carbon structure?
kinks
What does the lipid structure contain?
- carboxylic acid group - acid = H+ donor
- Forms reversible ester bonds with -OH groups (e.g. glycerol)
- Forms thioester bonds with -SH (sulphydryl) groups (e.g. CoA)
What are the 8 classes of lipids?
- fatty acyls
- glycerolipids
- glycerophospholipids
- sterol lipids
- sphingolipids
- saccharolipids
- prenol lipids
- polyketides
Give an example of saturated fatty acid:
- stearic acid
- octadecanoic acid
Give an example of monosaturated fatty acid:
- oleic acid
- 9Z-octadecenoic acid
Give an example of polysaturated (PUFA) fatty acid:
arachidonic acid
Give an example of essential fatty acid:
- alpha-linolenic acid
- gamma-linolenic acid
What are essential fatty acids?
- not produced by body
- used to produce eicosanoids and endocannabinoids
what are eicosanoids used for?
- inflammation
- control of vasodilation (BP)
What is the structure of a glycerolipid made of?
- free fatty acid
- glycerol
- ester bond
What are glycerolipids involved in and its properties?
- energy storage
- lipid synthesis via photosynthesis - carbohydrates
- physical properties, determined by saturation
- of acyl chains
- viscous with melting point
Since fatty acid is a carbon fuel source, how kJ is in palmitic acid?
19.46 kJ/LO2
What are the type of lipases releasing fatty acids and what are the functions if any?
- Pancreatic lipase - fatty acids for transport into gut lining cells (enterocytes)
- Hormone sensitive lipase - fatty acid in adipocytes, turned on by PKA
- Lipoprotein lipase
- Lysosomal lipase - in lysosome hydrolyses cholesterol esters and triacylglycerols delivered on LDLs
Where is serum albumin made and what is it?
- made in liver
- most abundant protein in blood
- carrier protein for fatty acids and others
- deliver fstty acids to/from adipocytes and skeletal muscles
how much serum albumin is there in blood?
35-50g/l
How are triglycerides carried around the body?
in complex with proteins lipoprotein particles (e.g. VLDL)
How can fatty acids enter cells?
have charged carboxylic acid groups and enter cells via channel protein (e.g. CD36)
How do you activate hormone sensitive lipase?
- adrenaline
- glucagon (liver, kidney)
When there’s not enough glucose, what happens to fatty acids?
ß-oxidation of fatty acids for energy release, you get acetyl-coA
What 3 areas does acetyl-coA contribute to?
- cholesterol synthesis
- fatty acid synthesis, lipogenesis
- Krebs (TCA) cycle - ATP energy production
Where does the fatty acid activation by coA addition take place at?
in the cytoplasm
What catalyses the fatty acid activation by coA addition?
acyl-coA synthetase long chain enzymes (ACSL)
How do you move acyl-coA into the mito. matrix?
the coA is swapped with molecule of carnitine
How many enzymatic reactions of ß-oxidation are there?
4
What is mitochondrial trifunctional protein (MTP)?
aka TFP, heterotrimer localised to the inner mitochondrial membrane and catalyses 3 out of 4 steps in ß-oxidation
What is the structure of mitochondrial trifunctional protein (MTP)?
4 alpha subunits, 4 ß subunits
The activation with coA and carnitine transfer only applied to?
long-chain fatty acids C12-C20, medium C8-C10 and short chain fatty acids can enter the mito. directlky for ß-oxidation
In the ß-oxidation sequence, what do unsaturated fatty acids tend to have?
cis double bonds that have to be made trans to enter 2nd step in the oxidation
What does the close contact of peroxisomes and mitochondria do?
facilitates transfer of substrates to mitochondria
Where are FFA receptors found and what does their signalling do?
on pancreatic cells, signalling cascade leads to insulin secretion
What is peroxisome proliferator-activated receptor γ (PPARγ)?
- nuclear transcription factor that binds and is activated by arachidonic acid.
- binds DNA at specific PPRE elements
What is protein acylation?
- post-translational modification of proteins
- covalent addition of lipid to a protein
- most common is addition of palmitic acid to cysteine SH groups on protein
- termed = s-palmitoylation
Describe insulin:
- signalling molecule, binds to surface receptors
- peptide hormone produced in pancreas
- increases glucose transport into cells
- inhibits activation of hormone sensitive lipase
- acetyl coA from glucose available for fatty acid (lipogenesis) and cholesterol synthesis
Why is lipogenesis upregulated in cancer?
lipids needed for cell membranes (proliferation) and signalling phospholipids (proliferation, survival, motility)
How many times does the cycle reiterate to generate 16C fatty acid palmitate?
6 times
In the involvement of ATP citrate lyase (ACLY), how is the citrate first transported out of the mitochondria?
by citrate transporter protein (CTP1)
What is acetyl-coA carboxylase?
key enzyme that converts acetyl-coA into malonyl-coA
- CO2 released later
- biotin is a co-factor
- committed step in FA synthesis
What are the 2 isoforms of ACC (acetyl-coA carboxylase)?
ACC1 and ACC2
What is the function of ACC1?
- lipogenic tissue
- generates malonyl coA for fatty acid synthesis
What is the function of ACC2?
- cardiac, muscle tissue
- generates malonyl coA at mitochondria outer membrane
What does malonyl coA inhibit?
carnitine palmitoyltransferase 1
Which hormones stimulate ß-oxidation to activate AMP-activated protein kinase to induce phosphorylation and inhibition?
- adrenaline
- noradrenaline
- glucagon
In the regulation of acetyl CoA carboxylase, what is protein phosphatase 2 activated by, and what happens as a result?
- insulin receptor activates it
- dephosphorylates the enzyme
- activation leads to more lipogenesis
What is FA synthase enzyme?
- enzyme complex
- excludes acetyl-coA carboxylase
- exists as dimer of two complete, anti-parallel complexes
- cytosolic
Which step in FA synthesis iterates many times to grow the FA backbone?
step 2, the setting up of malonyl-ACP
What is b-ketoacyl-ACP?
- its a condensing enzyme
- part of FA synthase complex
In FA synthesis, what is used to reduce the ß-carbonyl to hydroxyl group?
NADPH
What cleaves the ACP from palmitoyl-ACP?
thioesterase
Give the summarised steps of FA synthesis:
- Set up malonyl-ACP
- Condense them, giving acetoacetyl-ACP and CO2
- Use NADPH to reduce ß-carbonyl to hydroxyl group
- Remove the hydroxyl group as H2O leaving a double bond
- Use another NADPH to reduce the double bond
- Repeat step 1 using the new 4-carbon butyryl-ACP in place of acetyl-ACP
- Thioesterase cleaves ACP from palmitoyl-ACP, releasing palmitate
Where do elogations by elongase enzymes take place at?
endoplasmic reticulum
