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Biochemistry > Triglyceride, Phospholipid, and Sphingolipid Metabolism > Flashcards

Triglyceride, Phospholipid, and Sphingolipid Metabolism Flashcards

1
Q

Where does phosphatidylethanolamine synthesis begin?

A

The cytoplasm

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2
Q

How does short term fatty acid metabolic regulation work? What mechanisms?

A

Allosteric regulation, covalent modification of AMPK (AMP kinase), and hormones

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3
Q

How does long term fatty acid metabolic regulation work? What mechanisms?

A

Changes in gene expression

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4
Q

Which regulatory hormones phosphorylate protein kinases? Which hormones dephosphorylate?

A

Glucagon/epinephrine phosphorylate

Insulin dephosphorylates

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5
Q

What are the allosteric modulators of FA metabolism?

A

NADH, thiolase, malonyl-CoA, long chain fatty acids

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6
Q

What inhibits beta-hydroxyacyl-CoA-dehydrogenase? When does this reaction occur?

A

NADH

Third reaction in beta-oxidation

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7
Q

What inhibits thiolase? When does this reaction occur?

A

Acetyl Co-A

Fourth step in beta-oxidation

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8
Q

What inhibits CAT-I? What hormones affect this? What is CAT-I?

A

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

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9
Q

What inhibits ACC? What is ACC?

A

ACC = Acetyl-CoA Carboxylase

High long chain fatty acid acyl-CoA level inhibits ACC (depolymerization) -> blocks FA synthesis

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10
Q

What activates AMP-activated protein kinase (AMPK)?

A

High AMP/ATP ratio

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11
Q

When does AMP level increase?

A

In response to stress, nutrient deprivation, and prolonged exercise

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12
Q

What does AMP do?

A

Promote phosphorylation reactions and inhibit dephosphorylation

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13
Q

What does AMPK do?

A

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

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14
Q

How does insulin regulation of FA metabolism work?

A

Insulin- promotes fat synthesis by signal transduction; activates ACC by dephosphorylation; triggers GLUT4 to cell surface

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15
Q

How does epinephrine/glucagon regulation of FA metabolism work?

A

Increases lipolysis by stimulating phosphorylation

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16
Q

How does long term regulation of FA metabolism work (w/transcription factors)

A

Insulin upregulates genes that code for enzymes in FA and NADH synthesis

Glucagon and Long-chain FAs inhibit this

17
Q

What are the two classes of transcription factors involved in FA metabolism?

A

SERBPs and PPARs

18
Q

What are lipoproteins?

A

Group of molecular complexes found in the blood plasma of mammals

Transport lipid molecules through the bloodstream from organ to organ

19
Q

Where are protein components for lipoproteins synthesized? What are they called

A

Apolipoproteins

Synthesized in liver (VLDL) or intestine (chylomicrons)

20
Q

What is the endogenous lipid transport pathway?

A

Transport of recently synthesized TG packaged in VLDL from liver to other tissues?

21
Q

What is the exogenous pathway?

A

Transport of recently synthesized TG packaged in chylomicrons to other tissues

22
Q

How are lipoproteins classified?

A

According to their density

low density = more triacylglycerols

high density = more proteins

23
Q

What are the classes of lipoproteins? What do they do?

A

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

24
Q

What are the apolipoproteins that correspond to each lipoprotein? What do they do?

A

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

25
Q

What are the steps in the endogenous pathway?

A

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

26
Q

How does phospholipid synthesis work?

A

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

27
Q

How are PE (phosphatidylethanolamine) and PC (phosphatidylcholine) synthesized?

A

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)

28
Q

How is PS (phosphatidylserine) synthesized?

A

PS is generated by reversible polar head group exchange with PE (catalyzed by PE-serine transferase)

29
Q

What is phospholipid turnover?

A

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

30
Q

How does phospholipid degradation work?

A

5 phospholipases degrade specific bonds

PLA1, PLA2, PLB, PLC, PLD

31
Q

How are sphingolipids metabolized?

A

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
32
Q

What is a cerebroside?

A

Sphingolipids [ like phospholipid, but nonionic ] with monosaccharide for their head group (nonionic)

33
Q

Tay-Sachs is what type of disease? What enzyme is responsible?

A

Sphingolipid storage disease

GM2 ganglioside accumulates

Beta-hexosaminidase

34
Q

Which apolipoprotein is responsible for binding to LDL receptor?

A

B-100

35
Q

Which enzymes are involved in the phospholipid metabolism that is necessary for alteration of membrane fluidity

A

Phospholipases and acyltransferases

36
Q

Ceramide synthesis begins with the condensation of…

A

Palmitoyl-CoA and serine

37
Q

How are sulfatides synthesized?

A

Sulfatides (sulfated cerebrosides) are synthesized
when galactocerebroside reacts with the sulfur
donor 3’-phosphoadenosine-5’-phosphosulfate

38
Q

How are gangliosides synthesized?

A

Gangliosides: Sphingolipids that possess

oligosaccharide groups with one or more sialic acid residues

Biochemistry (43 decks)

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