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Biochemistry > Block 3 Fatty Acid Synthesis > Flashcards

Block 3 Fatty Acid Synthesis Flashcards

1
Q

What are the substrates for lipogenesis?

A

Carbs, AAs, EtOH; glucose provides glycerol backbone

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2
Q

When and where does lipogenesis occur? What stimulates it?

A

In fed state, stim by insulin (greater with high carb vs. high fat diet), in liver, adipose depot, lactating mammary gland

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3
Q

What are the major FAs synth in the body?

A

Palmitate (16:0) (except mam gland makes C8-12 also), elongate to stearate (18:0) or shorten to myristate (14:0)

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4
Q

What is the product of stearate and palmitate desaturation?

A

Stearate (18:0) to oleate (18:1); palmitate (16:0) to palmitoleate (16:1)

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5
Q

Where does FA synth occur? What is the activated donor? What are the required cofactors? What is the product?

A

In cytosol, FA + ACP, + malonyl-ACP using NADPH + H+ -> elongated to palmitic acid (C16)

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6
Q

What is the first step of FA synthesis?

A

Formation of malonyl-CoA using biotin to bind intermediate of rxn from AcCoA, using AcCoA carboxylase (spont DC later drives condensation)

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7
Q

What are acetyl- and malonyl-transferase? What’s the next enzyme in FA synth?

A

Attach AcCoA or malCoA to ACP, then react with acyl-malonyl ACP condensing enzyme to become acetoacetyl-CoA

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8
Q

What are the three steps following condensation to aaCoA in FA synth?

A

1) aaACP + NADPH reduction to D3HB-ACP
2) dehydration to crotonyl-ACP
3) + NADPH reduction to butyryl-ACP (now substrate for further condensation with malCoA)

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9
Q

What is the last enzyme and reaction of FA synth?

A

Thioesterase hydrolyzes C16-acyl-ACP to palmitate and ACP

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10
Q

Describe the makeup of FA synthase.

A

Multienzyme complex: malCoA transferase, b-ketoacyl red (ACP linker), b-hydroxyacyl-dehydratase, enoyl red, AcCoA transacetylase, b-ketoacyl synthase (cys link, condenser), ACP with P-pantetheine linker to all active sites)

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11
Q

How is FA synthase regulated?

A

Insulin stimulates FAS expression via USF and SREBP (suppressed by PUFA in liver), exp of SREBP-1 (and FAS) in fat inh by leptin (produced by fat in response to excess fat storage)

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12
Q

What are the required substrates for synthesis of palmitate?

A

8 mol AcCoA, 14 NADPH, 7 ATP

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13
Q

What is a citrate carrier? How does it work?

A

Moves AcCoA from mito to cytosol by converting to citrate with OAA. In cytosol, back to OAA + malate DH -> malate + malic enzyme -> NADPH + CO2 + pyr -> into mito -> OAA by PDC

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14
Q

What are the two sources of cellular NADPH?

A

Oxidative branch of PPP, malic enzyme pathway (transhydrogenase pathway) using malate DH and malic enzyme

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15
Q

What is the major regulated step of FA synth? How is it regulated?

A

AcCoA carboxylase, by P and allosterically by local metabolites

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16
Q

How does conformation of AcCoA-C change in active vs. inactive forms?

A

Active: multimeric filamentous complexes, protein P-ase 2A
Inactive: dissociation to monomeric form (protomer), AMP-activated PK

17
Q

How does citrate affect AcCoA carboxylase?

A

Partially activates carboxylase when bound

18
Q

What activates PP (act AcCoA C) and PKA (inh AcCoA C)?

A

PP: insulin
PKA: AMP, glucagon, epi; inh by ATP

19
Q

How are FA >C16 elongated?

A

Enzymes on cytosolic face ER membrane add malonyl-CoA (2C), condensation driven by malCoA decarboxylation

20
Q

How are FA desaturated?

A

Introduce double bonds at specific positions using NADH & O2; not for all, so some PUFAs dietary essential (C12)

21
Q

How do FA oxidation and synthesis differ?

A

B-ox: in mito, FAD and NAD+ are e- acceptor, L-BHA group, C2 is AcCoA
Synth: in cytoplasm, ACP is acyl group carrier, NADPH is e- donor, uses D-BHA group, C2 is malCoA

22
Q

What are the major regulatory steps of FA breakdown, synth? How are both regulated?

A

Breakdown: transport of AcCoA into mito
Synth: AcCoA carboxylase
Response to energy state of cell, availability of precursors for anabolism, globally by hormones

23
Q

How does FA synth inhibit FA B-ox?

A

Malonyl-CoA (product 1st rxn) inhibits carnitine-acyl-transferase-1 (Fa-CoA -> Fa-carnitine)

24
Q

How are synthesized FAs stored? What is the pathway?

A

Liver, adipocytes as TAG; Gly-3P (from DHAP) + acylCoA -> 1-acyl-gly-3P (lyso-PA) + acylCoA -> PA - PO4 -> 1,2-DAG + acylCoA -> TAG

25
Q

How does FA storage differ in liver and small intestine?

A

Liver: can P and recycle free glycerol
Small: reacylates 2-MAG

Biochemistry (17 decks)

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