lipid degradation: fat digestion + mobilization Flashcards
water soluble enzymes have a difficult time accessing fats for beta oxidation. how do we combat this?
the fats must be emulsified first
what does movement of fats through the blood require
requires associated water soluble proteins
stable C-C bonds require activation by ___ before oxidation
CoA
why is it called b-oxidation
CoA binds to the carboxyl at C1 first. This allows oxidation at C3, aka the b carbon
list 4 sources of fatty acids for b oxidation
fats in the diet, fats stored in cells as lipid droplets, fats synthesized in the liver from excess carbs that can be exported elsewhere, fats obtained by autophagy (recycled lipids from an organelle membrane)
humans in industrialized countries get __% of energy from dietary fats
40%
how does starvation affect autophagy in energy production
starvation can increase the use of autophagy
lipid droplets in adipocytes are full of ____ and ____
cholesteryl esters and TAGs
T or F: lipid droplets in adipocytes are surrounded by a phospholipid bilayer
false; they’re surrounded by a phospholipid monolayer
what are perilpins?
they’re proteins that cover the monolayer membrane of lipid droplets in adipocytes
function of perilipins?
they prevent lipid degradation (they protect the lipid droplets in adipocytes)
perilipins are bound to an accessory protein called ___
CGI
list two hormones that signal the need to bring TAGs out of storage and use them for energy
glucagon and epinephrine
why does glucagon serve as a signal to bring TAGs out of storage + use for energy
you’re hungry = need to access TAGs for energy
why does epinephrine serve as a signal to bring TAGs out of storage + use for energy
needed for adrenaline = require TAGs for energy
describe briefly what needs to happen to bring TAGs out of storage + use them for energy
hormone signals need to remove perilipin from the lipid droplet surface, and then TAGs need to be cleaved into free FAs to move through the bloodstream
describe the steps leading up to perilipin dissociation from CGI protein on lipid droplets
glucagon is involved in a GPCR/G protein signalling pathway, producing adenylyl cyclase, which in turn produces cAMP from ATP. cAMP stimulates PKA, which phosphorylates Hormone Sensitive Lipase (HSL) and perilipins. Phosphorylated perilipins dissociate from CGI protein
in the pathway of perilipin dissociation from CGI (to access TAGs for energy), what two things does PKA phosphorylate to release perilipin
Hormone Sensitive Lipase (HSL) and perilipin
in the pathway of perilipin dissociation from CGI (to access TAGs for energy), describe the steps that occur once perilipin is no longer bound to CGI
CGI activates ATGL, which converts TAGs into DAGs. Phosphorylated HSL-perilipin converts DAGs into MAGs. MGL converts MAGs to free FA + glycerol. Free FAs leave adipocyte and travel through the blood bound to serum albumin, and will enter target tissues by a FA transporter
in the pathway of perilipin dissociation from CGI (to access TAGs for energy), what is ATGL and what does it do
adipose TAG lipase. It converts TAGs to DAGs
in the pathway of perilipin dissociation from CGI (to access TAGs for energy), what converts DAGs to MAGs
phosphorylated HSL-perilipin
in the pathway of perilipin dissociation from CGI (to access TAGs for energy), what converts MAGs to FAs+glycerol
MGL: MAG lipase
in the pathway of perilipin dissociation from CGI (to access TAGs for energy), why must free FAs travel through the blood bound to serum albumin
without the serum albumin, FA is too hydrophobic to be able to travel through the blood
where is serum albumin produced
the liver
how many fatty acids can one serum albumin bind to
7
what target tissues does albumin bring FAs to
skeletal muscle, heart, kidney
what happens to serum albumin when there is high blood glucose
it becomes glycated
what is glycation
the non-enzymatic addition of reducing sugar products to amine groups on proteins and disrupts protein function + can contribute to tissue damage
T or F: glycation involves enzymes to reduce sugar products to amine groups on proteins
false; no enzymes are required
is glycation good or bad? explain
bad: if you have a lot of sugars in your blood and they start randomly sticking to stuff like serum albumin, the function of serum albumin will be disrupted
list 4 diabetes symptoms that glycated albumin contributes to
retinopathies, renal disease, coronary heart disease, neuropathies
glycerol only represents __% of the total energy stored in TAGs
5%
after FAs and glycerol are released from lipid droplets, where does the glycerol go
to the liver
list 2 things that can happen once glycerol from broken down lipid droplets is shipped to the liver
- it can be phosphorylated and oxidized to DHAP, which can be used for glycolysis or GNG
- it can be phosphorylated by glycerol kinase to make glycerol-3-phosphate for glycerophospholipid synthesis
once glycerol from broken down lipid droplets is in target tissues, where does it need to go
the mitochondrial matrix
in animals, where does FA oxidation take place
mitochondrial matrix
T or F: FAs with 12C or less can cross the mitochondrial membrane unassisted
true
T or F: FAs with 14C or more can cross the mitochondrial membrane unassisted
false; they require multiple enzymatic steps to enter the matrix
what is the name of the steps required to get 14C+ FAs into the mito matrix in preparation for oxidation
the carnitine shuttle
briefly list the 4 basic steps of the carnitine shuttle
FA is esterified to CoA, CoA is swapped for carnitine, FA-carnitine passes both mito membranes, carnitine is re-swapped for CoA
describe step 1 of the carnitine shuttle
FA is converted to fatty acyl-CoA via acyl-CoA synthetases on the OMM. Costs 2 ATP equivalents
how much ATP (if any) does step 1 of the carnitine shuttle cost
2
describe step 2 of the carnitine shuttle starting with fatty acyl-COA
the CoA is exchanged via transesterification for a molecule of carnitine. The FA transiently attaches to the carnitine OH group, catalyzed by carnitine acyltransferase I in the OMM. Carnitine ester can now enter the IMS through large pores, then the matrix through a carnitine transporter on the IMM
describe step 3 of the carnitine shuttle
fatty acyl group is transferred from carnitine back to CoA by carnitine acyl transferase II on the inner face of the IMM. Carnitine returns to the cytosol through the same transporter, and now we can do b-oxidation
how/where is carnitine synthesized
synthesized from lysine in the liver/kidney/brain or obtained in the diet by red meat and dairy
list 3 things that are associated with low carnitine levels
premature infants, diabetics, elderly
list 4 things that carnitine supplements have been shown to reduce
hypertension, diabetic ketoacidosis, insulin resistance, cardiac arrhythmias
what are the CoA and fatty acyl-CoA stores in the cytoplasm used for
FA biosynthesis and elongation
what are the CoA and fatty acyl-CoA stores in the mito matrix used for
FA oxidative degradation
what is the commitment step in FA oxidation
conversion of the fatty acyl-CoA to the carnitine ester
why does malonyl-Co inhibit carnitine acyltransferase I
we use lots malonyl-CoA for FA synthesis, and it is committed to do so already, so there’s nothing else we can do with it, and synthesis and breakdown do NOT happen at the same time. The commitment step of synthesis inhibits the commitment step of degradation
what would happen if you have a defective CGI protein
you cannot access DAGs
Why would muscle weakness during prolonged exercise be a symptom of a carnitine acyltransferase deficiency?
during prolonged exercise, energy storage is from FAs (not glycogen anymore), so FAs are undergoing oxidation.
Patients with a carnitine acyltransferase deficiency still can have some beta oxidation of fatty acids during exercise…how?
fatty acids that are long have to go through the whole pathway we covered, but smaller FAs don’t need to do that and can go right to the mitochondria
