Synthesis of Fatty Acids and Phospholipids

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1

Precursor to Fatty Acids and Sterols

Acetyl-CoA

2

Requirements (2) for synthesis of Fatty Acids and Sterols

ATP and NADPH

3

Location of Fatty Acid synthesis in animal and yeast cells

Cytosol

4

Location of Fatty Acid synthesis in plant cells

Cholorplast

5

What is the Rate-Limiting (committed) step in Fatty Acid Synthesis

Reaction 1: Malonyl-CoA synthesis via Acetyl-CoA Carboxylase

6

Regulators of Malonyl-CoA Synthesis

1) Citrate Stimulates
2) Palmitoyl-CoA inhibits

7

Acyl Carrier Protein (ACP) function....

Flexible arm connected to FAS complex and carries intermediates through synthesis of Palmitoyl-CoA

8

Fatty Acid Synthase Complex

Enzyme that intermediates remain attached to via ACP. There are 7 enzyme

9

Product of Fatty Acid Synthesis

Palmitic Acid (16-C)

10

Carbon Order of FA Synthesis

C-16 and C-15 synthesized first, C-2 and C-1 Synthesized last

11

Which carbons are derived directly from Acetyl-CoA?

C-15 and C-16

12

After initial addition of Acetyl-CoA to FA, how are sequential Carbons added to the chain?

Acetyl-CoA is first activated to malonyl-CoA, a 3-carbon compound, by the addition of a CO2. Both the Malonyl and Acetyl are attached to the FAS and the malonyl then gets condensed to the acetyl group, this complex is reduced, dehydrated, and reduced to butyryl-ACP. Sequential condensations then happen

13

The main site for the synthesis of fatty acids in a plant cell is the:

Chloroplast

14

Why are dietary fats essential?

They provide essential fatty acids such as linoleate and linolenate, which is required for EICOSANOID synthesis. We cannot synthesize them

15

Source of NADPH in the liver and mammary gland:

PPP

16

Source of NADPH in the Adipose tissue

Malate Shuttle Enzyme: Malate -> Pyruvate

17

Source of NADPH in plant chloroplasts

Photosynthetic electron transfer

18

Acetyl-CoA is generated primarily in mito, but is needed in cytosol for FA Synthesis, what is the mechanism whereby it enters the cytosol

Acetyl-CoA condenses with oxaloacetate to form citrate with is transported into the cytosol where it is cleaved to generate Acetyl-CoA and oxaloacetate in an ATP dependent reaction

19

Positive regulator Acetyl-CoA Carboxylase:

Insulin

20

Negative regulators (2) of Acety-CoA Carboxylase:

1) Phosphorylation (inactivation) of glucagon cAMP
2) Palmitoyl-CoA feedback inhibition

21

Function of Trans-Acylases

Catalyze exchange from CoA to ACP (This is done to Acetyl-CoA and Malonyl-CoA).

22

Site of elongation after Palmitic Acid leaves cytosol:

Endoplasmic Reticulum

23

What is the regulator of FA Synthesis/Oxidation

Malonyl-CoA stops B-Oxidation (Inhibitor)

24

Location of FA Synthesis

Cytoplasm

25

Location of FA Oxidation

Mitochondria

26

Intermediate Carrier of FA Synthesis

ACP-SH

27

Intermediate Carrier of FA Oxidation

CoASH

28

Importance of sphigolipids

To form membranes

29

Importance of gangliosides

Make up brain lipids

30

Tay-Sachs, Fabrys, Sandhoffs, Gauchers, and Niemann Pick Diseases

Accumulations of gangliosides due to deficiency of enzymes that are supposed to degrade them