Fatty Acids Synthesis

What are the two steps in Fatty Acid Synethesis?

production of malonyl-CoA (precursur); elongation

Draw out the process of Fatty Acid synthesis of malonyl CoA

1. Citrate in mitochondria

2. Citrate —> acetyl CoA + OAA via citrate lysis; requires ATP, CO2 released

3. Acetyl Coa —> Malonyl CoA via Acetyl CoA Carboxylase; Biotin and ATP required;

4. Malonyl CoA —> palmitate via Fatty acid Synthase

5. Palmitate then becomes VLDL

1. OAA cleaved from Citrate

2. OAA —> Malonyl CoA via cytosilic malate dehydrogenase; needs NADH

3. Malate —> pyruvate via malic acid; requires NADP+, release CO2

In Fatty Acid Synthase, where is the growing Carbon chain attaching to? What is the cost of this?

acytl-carring protein; costs 2 NADPH

When is citrate transported out of the mitochondria? What induces citrate lysase? What activates pyruvate carboxylase

when citrate is in excess. Citrate Lyase is induced by ATP. High Acetyl-CoA = pyruvate carboxylase is activated

What pathways do NADPH go into?

reductive synthesis of FA, steroids, sterols

detoxification of reactive oxygen intermediates

cytochrom p450 system

how does insulin regulate the pyruvate dehydrogenase complex? What does insulin also induce synthesis of?

insulin activates PDHC phosphatases which dephosphalize PDHC complex, activating it

Insulin also induce synthesis of G6P dehydrogenase (PPP), Malic Enzyme, citrate lyase

How is citrate accumulated?

through inhibition of isocitrate dehydrogenase (NADH)

What is the rate limiting step of FA Synthesis? Describe this reaction? Describe how it is regulated

Acetyl-CoA carboxylation; this makes maloynl CoA with help of Biotin, ATP, and CO2

Regulated by phosphorylation

1. inhibited by AMP-activated Protein Kinase

2. Allosterically activated by Citrate, allosterically inactivated by palmitoyl-CoA

3. Induced by Insulin

Describe the mechanism in which two carbons are added

1. Malonyl-CoA’s acetyl group gets attache to the ACP (acyl-carrier protein) of FA-synthase.

2. Then Malonyl attach to phosphopantetheinyl residue of the ACT of the Fa synthase

3. The acetyl group condenses with the malonyl to form 3-ketoacyl group (CO2 gets release).

4. The ketone group gets reduced to an alcohol (NADPH —> NADP+), then dehydration happen,

5. then the double bond gets reduced (NADPH —> NADP+)

what type of FA occur especially in the brain? How does activated palmitate be elongated? What is the major elongation step?

Very long chain FA (22-24); palmitate can be elongated two carbons at a time in the ER. The Malonyl CoA donates the two-carbon units.

Major step = plamityol-CoA (C16) —> Stearyl-CoA (18)

What happens in the ER?

elongation of FA and desaturation of FA

What does desaturation of FA require?

O2

Cyctochrom B5 (cytochomes are synthesized from succinyl CoA)

NADH

What are the three most common desaturation reaction?

1. placement of double bond between carbons 9-10 leading to palmitoleic acid

2. the conversion of stearic acid to oleic acid (18:1)

3. other positions that can be desaturated are C5 and C6

what type of fatty acids are precursor to eisocanoids?

omega 3 and 6

Describe the conversion of linoleic acid to arachidonic acid

lionleic acid gets desaturated at C6, Elongated by 2 carbons, desaturated at C5

why is G-6-P important in fatty acid synthesis?

leads to the PPP pathway to make more NADPH.

Which metabolic pathways produce NADPH?

PPP and the trans-hydrogenation pathway (OAA —> Malate —> Pyruvate)