Biosynthesis of FAs Flashcards

1
Q

Effect of unsaturation on melting point

A

Decrease the melting temperature of fatty acid

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2
Q

What effect does the cis double bond in an unsaturated FA have on cell membranes?

A

Increases fluidity of the cell membrane, making it more flexible

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3
Q

How to name FA

A
  1. Use the carbon numbers starting with carboxyl group as C1 (including carboxyl group) so 20:4(5,8,11,14) = 20 carbons, with 4 double bonds and the locations are in parentheses
  2. 2nd carbon is alpha and keep going through Greek alphabet. Methyl group is always omega, so Omega-6 = 6 carbons back from the final C.
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4
Q

Lineoleic acid

A
  • Precursor of arachadonic acid, which is the substrate for prostaglandin synthesis
  • Also the precursor of other omega-3 FA, and is important for growth and development
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5
Q

Important functions of FA

A
  1. Major hydrophobic components of all cell membranes
  2. Major storage form of metabolic energy, TAGs are main caloric reserve
  3. Essential precursors for the eicosanoids
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6
Q

Major sources of FA

A
  1. Biosynthesis from small molecule intermediates derived from metabolic breakdown of sugars, AA, and fats
  2. Diet essential FA (Linoleic and linoleic acid)
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7
Q

When are FA synthesized?

A

When dietary calories are in excess and you get excess Acetyl-CoA

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8
Q

How does FA synthesis lead to stimulation of gluconeogenesis?

A
  1. High ATP inhibits TCA cycle, which then allows citrate to accumulate
  2. Citrate is then passed on for further FA synthesis as well as regeneration of OAA for gluconeogenesis
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9
Q

What is the RLS for FA biosynthesis?

A

Formation of malonyl-CoA

Can also inhibit the enzyme with LCFAs

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10
Q

FAS

A
  1. 7 different enzyme activities
  2. Acyl Carrier Protein (ACP)
  3. Performs all the steps to convert malonyl CoA to a FA
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11
Q

Malonyl CoA to FA

A
  1. Regulated by FAS
  2. Synthesized 2 carbons at a time (4-step repeating cycle)
  3. Repeat cycle 7 times to produce palmitic acid (16:0), which can then undergo separate elongation and/or desaturation to yield other FA molecules
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12
Q

Synthesis of palmitate by FAS

A
  1. Condensation to form acetoacyl ACP
  2. Reduction of the keto group to an alcohol
  3. Dehydration to introduce a double bond
  4. Reduction of the double bond

(numbering is from his diagram in PPT)

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13
Q

Elongation and desaturation

A
  • Occur in the ER or mitochondria

- Performed by FA elongases

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14
Q

Diet and metabolic conditions for FA synthesis

A
  1. High carb = high pyruvate and acetyl CoA in mitchondria –> stimulate FA synthesis
  2. High fat/low carb diet = low pyruvate flux –> reduced FA synthesis
  3. Hormonal environment = high insulin favors lipogenesis and decreased FA biosynth,
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15
Q

Short-term regulation of FA biosynthesis

A

Citrate:

  1. Availability of cytosolic citrate determines amount available for synthesis
  2. Citrate activates ACA carboxylase and increase Vmax

Palmitoyl CoA

  1. Inhibits ACA carboxylase
  2. Cytosolic levels are high in starvation or high fat diets

Insulin and glucagon:

  1. Insulin promotes FA synthesis by dephospho ACA carboxylase
  2. Increases intracellular cAMP which leads to phospho of ACA carboxylase
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16
Q

2 ways to make glycerol 3-phosphate in liver

A
  1. Direct phosphorylation of glycerol to glycerol phosphate by glycerol kinase (not present in adipose, so it can only be done in liver)
  2. Glycolysis dihydroxyacetone phosphate –(glycerol-p-dehydrogenase)–>Glycerol phosphate
17
Q

Storage of FA as TAGs

A
  1. Synthesis from G-3-P and FA CoA includes addition of 2 FA from Fatty acyl CoA, then removal of phosphate to add 3rd FA
  2. FA on C1 is saturated, then 2 is unsaturated, and 3rd carbon is either
  3. TAGs are major storage form of FAs
  4. TAGs synthesized in the liver and packaged with cholesterol esters, cholesterol, or PLs to lead to VLDLs
18
Q

How does chronic alcoholism cause hyperlipidemia?

A
  1. Ethanol oxidized to acetate
  2. Increased NADH/NAD+ slows TCA cycle and FA oxidation
  3. Glycerol 3-P and FA –> TAGs
  4. Liver secretes abnormally high levels of VLDL.

Because liver dysfunction impairs protein synthesis and the liver cannot produce and secrete VLDL –> increased fat buildup

19
Q

Properties of FAs

A
  1. Hydrophobic hydrocarbon chain
  2. Charged COO- group ionized at pH 7 gives hydrophilicity (not dominant)
  3. Longer chain length = more insoluble in water
  4. Usually esterified in the form of TAGs