Triglyceride, Phospholipid, and Sphingolipid Metabolism Flashcards
Where does phosphatidylethanolamine synthesis begin?
The cytoplasm
How does short term fatty acid metabolic regulation work? What mechanisms?
Allosteric regulation, covalent modification of AMPK (AMP kinase), and hormones
How does long term fatty acid metabolic regulation work? What mechanisms?
Changes in gene expression
Which regulatory hormones phosphorylate protein kinases? Which hormones dephosphorylate?
Glucagon/epinephrine phosphorylate
Insulin dephosphorylates
What are the allosteric modulators of FA metabolism?
NADH, thiolase, malonyl-CoA, long chain fatty acids
What inhibits beta-hydroxyacyl-CoA-dehydrogenase? When does this reaction occur?
NADH
Third reaction in beta-oxidation
What inhibits thiolase? When does this reaction occur?
Acetyl Co-A
Fourth step in beta-oxidation
What inhibits CAT-I? What hormones affect this? What is CAT-I?
Malonyl-CoA (ACC product)
CAT-I = Carnitine-Acyl Transferase
High insulin/glucagon ratio leads to high malonyl-CoA level that causes the inhibition of beta-oxidation in liver
What inhibits ACC? What is ACC?
ACC = Acetyl-CoA Carboxylase
High long chain fatty acid acyl-CoA level inhibits ACC (depolymerization) -> blocks FA synthesis
What activates AMP-activated protein kinase (AMPK)?
High AMP/ATP ratio
When does AMP level increase?
In response to stress, nutrient deprivation, and prolonged exercise
What does AMP do?
Promote phosphorylation reactions and inhibit dephosphorylation
What does AMPK do?
Switches off anabolic pathways and switches on catabolic pathways
Inhibits FA synthesis by inhibiting ACC (phosphorylation)
Inhibits TG synthesis by inhibiting glycerol-3-phosphate-acetyltransferase
How does insulin regulation of FA metabolism work?
Insulin- promotes fat synthesis by signal transduction; activates ACC by dephosphorylation; triggers GLUT4 to cell surface
How does epinephrine/glucagon regulation of FA metabolism work?
Increases lipolysis by stimulating phosphorylation
How does long term regulation of FA metabolism work (w/transcription factors)
Insulin upregulates genes that code for enzymes in FA and NADH synthesis
Glucagon and Long-chain FAs inhibit this
What are the two classes of transcription factors involved in FA metabolism?
SERBPs and PPARs
What are lipoproteins?
Group of molecular complexes found in the blood plasma of mammals
Transport lipid molecules through the bloodstream from organ to organ
Where are protein components for lipoproteins synthesized? What are they called
Apolipoproteins
Synthesized in liver (VLDL) or intestine (chylomicrons)
What is the endogenous lipid transport pathway?
Transport of recently synthesized TG packaged in VLDL from liver to other tissues?
What is the exogenous pathway?
Transport of recently synthesized TG packaged in chylomicrons to other tissues
How are lipoproteins classified?
According to their density
low density = more triacylglycerols
high density = more proteins
What are the classes of lipoproteins? What do they do?
Chylomicrons- transport dietary TG and cholesterol to muscle and adipose tissues
Very-low-density lipoproteins
Intermediate-density lipoproteins (same as VLDL, but once they have delivered their triacylglycerol molecules)- transport lipids to tissues
Low-density lipoproteins- transport cholesterol and cholesterol esters to tissues
High-density lipoproteins- scavenge cholesterol and cholesterol esters from VLDL and LDL, and transport to liver and steroid synthesizing organs
What are the apolipoproteins that correspond to each lipoprotein? What do they do?
Nascent chylomicron- B48
Mature chylomicrons- B48, C-II, E (latter two acquired from HDL) - activates lipoprotein lipase (LPL)
Chylomicron remnants- B48, C-II, E (latter 2 from HDL) - binds liver specific receptor for removal from blood
Nascent VLDL- B100
Mature VLDL - B-100, C-II, E (latter 2 from HDL) - activates LPL
ILDL - B-100, C-II, E (latter 2 from HDL) - binds liver specific enzymes for removal from blood
LDL - B-100, C-II, E (latter 2 from HDL) - binds to LDL receptor to deliver cholesterol
What are the steps in the endogenous pathway?
Starts in liver with VLDLs assembled in cytoplasmic surface of hepatocyte ER
Nascent VLDLs in blood become mature VLDLs by acquiring apolipoprotein E-II and E from HDL
VLDLs unload TGs as they encounter Lipoprotein Lipase near the surface of target cells
FAs transported into adipocytes are converted back to TGs that coalesce into fat droplets
FAs transported into muscle cells are oxidized to generate energy
TG depleted VLDL (IDL) are endocytotically removed from the blood by the liver. This is mediated by apolipoprotein E.
TGs in IDLs are reduced by liver lipase
Once cholesterol content exceeds TG content, it is now a LDL
Liver releases LDLs into blood
LDL binds to receptor on target cells and releases cholesterol
How does phospholipid synthesis work?
Synthesis of phospholipids originates at the interface of Smooth-ER are cytoplasm
Unsaturated fatty acid replaces saturated FAs
This is accomplished by phospholipases and acyltransferases–allows to modify membrane fluidity
How are PE (phosphatidylethanolamine) and PC (phosphatidylcholine) synthesized?
1) Ethanolamine and choline enter the cell and are phosphorylated
2) Phosphoethanolamine and phosphocholine reaccts with CTP to form CDP-ethanolamine and CDP-choline (active intermediates)
3) CDP-ethanolamine and CDP-choline reacts with diacylglycerol to form PE and PC, respectively
Alternatively:
PC can also be synthesized from PE
PE is methylated in 3 steps by Phosphatidylethanolamine-N-methyltransferase to form PC (SAM is the methyl donor)
How is PS (phosphatidylserine) synthesized?
PS is generated by reversible polar head group exchange with PE (catalyzed by PE-serine transferase)
What is phospholipid turnover?
Rate at which all molecules in structure are degraded and replaced with newly synthesized molecules
Phospholipid turnover is RAPID
Two cell cycles are required to form the replacement of one-half of the total phospholipid molecules
How does phospholipid degradation work?
5 phospholipases degrade specific bonds
PLA1, PLA2, PLB, PLC, PLD
How are sphingolipids metabolized?
Animal sphingolipids possess ceramides–derivative of amino alcohol sphingosine
Ceramide synthesis begins with
the condensation of palmitoylCoA
with serine to form 3-keto
sphingosine
Sphingomyelin is formed when
ceramide reacts with
phosphatidylcholine
Galactoceramide and glucoceramide is formed when ceramide react with UDPgalactose and UDP-glucose, respectively
What is a cerebroside?
Sphingolipids [ like phospholipid, but nonionic ] with monosaccharide for their head group (nonionic)
Tay-Sachs is what type of disease? What enzyme is responsible?
Sphingolipid storage disease
GM2 ganglioside accumulates
Beta-hexosaminidase
Which apolipoprotein is responsible for binding to LDL receptor?
B-100
Which enzymes are involved in the phospholipid metabolism that is necessary for alteration of membrane fluidity
Phospholipases and acyltransferases
Ceramide synthesis begins with the condensation of…
Palmitoyl-CoA and serine
How are sulfatides synthesized?
Sulfatides (sulfated cerebrosides) are synthesized
when galactocerebroside reacts with the sulfur
donor 3’-phosphoadenosine-5’-phosphosulfate
How are gangliosides synthesized?
Gangliosides: Sphingolipids that possess
oligosaccharide groups with one or more sialic acid residues
