Biosynthesis Of Fatty Acids Flashcards

1
Q

Breakdown and synthesis of FAs are two separate pathways

What significant intermediate for synthesis is not present for breakdown and irreversible formation?

A

Malonyl coA

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2
Q

What are the active sites of acetyl coA carboxylase?

A

Biotin carboxylase domain

Activates co2
Attaches co2 to nitrogen in biotin ring with ATP help

Transcarboxylase domain
Transfers co2 from biotin to acetyl coA

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3
Q

Malonyl vs acetyl coA

A

Acetyl coA precursor
Just acetyl group plus s plus coA

Malonyl coA same as acetyl but plus co2
COOH group on end

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4
Q

Acetyl coA carboxylase differences in different species

Acetyl coA take hco3

A

Animal cells = cytoplasm for all steps

Bacteria = similar processs but separate polypeptide subunits for the three steps

Plants = both types

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5
Q

Why are fatty acids important?

A

Complex lipids components
E storage
Membrane structure
Signaling molecules

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6
Q

What is RLS for FA synthesis?

What is step stimulated by? Inhibited by?

A

Malonyl carboxylase synthesis

Stimulated by citrate
Inhibited by palmitoyl CoA

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7
Q

Biotinidase deficiency

A

Cannot recycle biotin

Enlarged liver and spleen
Dermatitis

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8
Q

Mammals FAS I details

A

Fatty acid synthase I
Multimeric complex = ensures efficiency
Only synthesizes even chain fatty acids

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9
Q

Sequence of events for FA synthase

A

KS = acetyl or Malonyl group added to ACP

condensation - co2 released (same co2 as added to acetylCoA in Acetyl coA carboxylase reaction)

KR = reduction of beta keto group (NADPH)

DH = dehydration - h2o released

ER = reduction of double bond (NADPH)

KS = translocation of butyryl group (resulting FA) to cys (SH) on KS

Recharge ACP with new Malonyl group

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10
Q

ACP Details

A

Contains covalent prosthetic group = 4’-phosphopantetheine = on ser side chain = vitamin B pantothenic acid
End of group is SH = how Malonyl groups are esterified

Delivers acetate (1st step) and malonate (following steps) to FaS

Shuttles growing chain through active sites during growth

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11
Q

MAT for FAS helps with what?

A

Charging of ACP

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12
Q

1 addition cycle for FAS

A

Adds two carbons
Uses 4H+ and 4e-
Releases 1CO2

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13
Q

Palmitate

A

16 C
Saturated
FAS I product

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14
Q

Palmitate production

A

8 acetyl coA + 7ATP + 14 NADPH + 14H+
—>
Palmitate + 8coA + 7ADP + 14 NADP + 6h2o

7 cycles acetylCoA carboxylase

7 cycles of condensation and reduction

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15
Q

How do liver cells Maintain high NADPH to NADP Ratio?

How do one do these things relate to FA synthesis?

A

PPP ox pathway
Malic enzyme = Malate to pyruvate

Pyruvate oxidation forms acetyl coA in mitochondrion
Also catabolism of AA carbon skeletons

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16
Q

Why is citric acid cycle important to FA?

A

Helps activate acetyl coA
Citrate production means acetyl coA —> coA-SH in mitochondrial Matrix

But
Citrate —> acetyl coA via citrate lyase in cytosol
Also produces OAA —> Malate
= RLS for FAS

17
Q

Liver, Mammary gland, kidney primary NADPH source

A

PPP

18
Q

Adipose tissue primary NADPH source

A

Malic enzyme

19
Q

FAS NADPH sources and ratios

A

1:1 PPP to malic enzyme

20
Q

What does citrate Allosterically activate.

What conditions encourage this?

A

Acetyl coA carboxylase

High ATP in mitochondria
High acetyl coA in mitochondria = more citrate produced

Citrate inhibits glycolysis enzymes

21
Q

What deactivates acetyl coA carboxylase?

Implications?

A

Glucagon
Epinephrine
High AMP

Palmitoyl AMP = product of Malonyl coA?

Implication: FAS is inhibited

22
Q

What does insulin activate?

A

Citrate lyase
= acetyl coA carboxylase production
= FAS activated

23
Q

Thioesterase

A

Hydrolitic
Uses H2O to break palmitate from ACP

24
Q

When FAS increased
What does this mean for E use?

A

Moving away from active E use, instead, E storage

25
Q

What does Malonyl coA inhibit?

A

Fatty acid oxidation

26
Q

Insulin and FAS

A

Synthesis is up

Breakdown is down

Insulin = in = keep E in

27
Q

Glucagon and FA

A

Synthesis is down

Breakdown is up

Glucagon = glucose wagon = we want to use energy

28
Q

How is FAS regulated?

A

NADPH availability - needed for condensation/ reduction cycle
ACC inhibited by glucagon, epinephrine
ACC activated by insulin and citrate

29
Q

Elongases

A

Facilitate elongation…

30
Q

Desaturation is reductive or oxidative?

A

Produces NADP
Oxidative

Carbon chains are reduced

31
Q

How do NSAIDs inhibit inflammation

A

Aspirin = inhibits via acetylating essential ser residue in cyclo oexygenase h2 prostaglandin synthase (COX)

Ibuprofen/ naproxen = mimic substrate structure

32
Q

ATP cost to transport 1 mitochondrial acetyl coA

A

1 atp