Exam 3 Lipid Metabolism II Flashcards
where are TAGs stored?
adipocytes/adipose tisse; infinite capacity
what are the 3 major lipases
- HSL (hormone sensitive)
- LPL (lipoprotein lipase)
- MAG Lipase
what stimulate HSLs
HORMONES
insulin, epi/noriepnephrine, glucagon
lipases do what
chip off FAs from glycerol, release FAs, and transport of FAs
how do short chain FAs get transporoted?
are soluble so transport by themselves
how do long chain FAs get transported?
complexed with albumin for transport
if long chain FAs were not complexed with albumin, what would happen?
would stick to blood vessels and form plaque
where does degradation of FAs begin?
Adipocytes
after action of HSL, what is the product
DAG
after action of LSL, what is the product
MAG
after the action of MAG lipase, what is the product
free glycerol and free FAs
what is the revised breakdown of TAGs
includes 4 major lipases now. 4th lipase is from -/- mice experiments.
what is the 4th lipase? and what does it do?
ATGL breaks TAGs into DAGs (same as HSL)
what are the ligands for GPCR?
glucagon, epinephrine
what stimulates glucagon and epinephrine release
hunger (glucagon) and exercise (epinephrine) = promote lipolysis in adipoctyes
what do GPCRs do?
activate protein kinase A
what does protein kinase A do
phosphorylates perilipin and HS lipase
phosphorylated perilipin is able to do what
associate with HSL/ATGL
what does glucagon and epinephrine release do to ATGL
hormones release an activator that binds to ATGL
what stimulates release of insulin
the fed state; a large meat
what is the receptor for insulin
insulin receptor RTK
what does insulin receptor RTK do
activates protein phosphatase (PP1)
what does PP1 do?
dephosphorylates; inactivates HSL
what does free glycerol go on to do
can be a source for new glucose (gluconeogenesis) or become pyruvate (glycolysis)
what organ takes up free glycerol?
hepatocytes; liver cell
free FAs are taken up by whom
other tissues that need them; muscle
what happens to free FAs when they are taken up
enter cell’s mito matrix to under go beta oxidation to make acetyl coA which enters CAC cycle to make energy
what do perlipins function to do?
proteins that surround lipid droplets in adipocytes and muscle cells containing TAGS to regulate physical access to HSL (regulate lipolysis)
overexpression of perlipin causes?
inhibits lipolysis as there is no access to TAGs
-/- of perilipin causes?
no perilipin = lots of breakdown and is now a target for obesity treatment
what is the order of a free FAs enter the mito matrix of a cell?
the cell’s membrane, the outer mito membrane, the inner mito membrane, and then the mito matrix
what occurs in the mito matrix when FAs reach there
beta-oxidation
free FAs are formed in the _ -> released into the _ -> taken up by various _ types
formed in adipocytes
released into blood stream
various cell types
what happens in phase I of FA breakdown
activation and transport to mito matrix
how does the FA get passed the outer mito membrane
the FA is activated by addition of coA (occurs in the cytosol)
how does FA-coA get passed the inner mito mem
carnitine displaces the coA to make permeable (happens in inter mem space)
outer mito mem is not permeable to
FA
inner mito mem is not permeable to
FACoA
what happens of phase II of FA breakdown
carnitine is lost and coA is added again undergoes beta oxidation
what are the products of beta oxidation
FADH2, NADH, and acetyl coA
what is the fate of acetyl coA
taken up by liver to make ketone bodies or enter TCA cycle to make energy
by using ATP, the carboxyl group of a FA when added with coA undergoes
FA activation via a thioester bond to make Fatty Acyl CoA
to get FAs into mito matrix, what must occur?
carnitine must replace coA
what is the enzyme to get FAs into the mito matrix
carnitine acyltransferase I
what is the rate limiting enzyme of FA degradation
carnitine acyltransferase I/CPT-1
what does malonyl coA do?
inhibits the rate limiting enzyme of FA degradation
once inside matrix, acyl carnitine (FA-carnitine) is acted upon what enzyme to do what?
acted upon by carnitine acyltransferase II to release FA-coA and carnitine
what are the 4 enzymes of phase 1
- FA-coA synthase
- CPT-1 (carnitine palmitoyltransferase I)
- CACT (carnitine-acylcarnitine translocase)
- CPT-II (carnitine palmitoyltransferase II)
what does FA-coA synthase do
activates free FAs to cross outer mito mem
what does CPT-1 do?
rate limiting enzyme in FA degradation forms FA-carnitine
what does CACT do
antiporter that shuttles carnitine
CPT-II does what
frees carnitine and makes FA-coA available for beta oxidation
beta oxidation cuts how many carbons at a time?
2
what are the 4 steps of beta oxidation
- oxidation
- hydration
- oxidation
- thiolysis
what is the enzyme responsible for the first step of beta oxidation
acyl coA dehydrogenase ACAD
what do the 4 main steps of beta oxidation generate
FADH2, NADH, and acetyl coA
where does FADH2 go
delivers e-s to CoQ of ETC
where does NADH go
delivers e-s to complex I of ETC
where does acetyl co go
enter TCA cycle
C16 FA-coA + 7FAD + 7NAD + 7coA + 7H20 ->
7FADH2 + 7NADH + 7(H+) + 8 acetyl coA
how much ATP did we use for activating an FA
2
why do ketone bodies form?
form as an energy source under conditions of starvation
ketone bodies have what properties as compounds
are water soluble and acidic
ketone bodies are only produced where
liver
ketone bodies provide energy for
peripheral tissues and brain during fasting and starvation
how do formation of ketone bodies start
starts with condensation of 2 acetyl coAs and a third acetyl coA
utilization of acetoacetate is a _ process
reverse
free FAs breakdown into _
acetyl coA
too much acetyl coA in the cell promotes synthesis of _
ketone bodies
after a first hours of fasting, the fuel supply is
blood glucose followed by glycogen stored in liver and muscle
after 1 day of fasting, fuel source is
TAGs in adipose tissue
after 3 days of fasting, fuel source is
ketone bodies made in liver and proteins in muscles
after 1-2 weeks of starvation, energy source is
brain switches to ketone body
after 2-3 months of starvation, fuel source is
proteins lead to coma and death
physiological ketosis is
mild to moderate increase in ketone bodies
pathological ketoacidosis
occurs when glucagon/insulin ratio ratio is increased (reduced OAA)
