Fatty Acid Synthesis

Question 1

Structure of fatty acids

Answer 1

hydrophobic hydrocarbon chain with a terminal carboxyl group that carries a negative charge at physiologic pH. S

Amphipathic nature (having both a hydrophobic hydrocarbon region and a hydrophilic carboxyl group)

Question 2

Saturated vs unsaturated fatty acids

Answer 2

Saturated= no double bond
Unsaturated= one or more double bond

Question 3

Are the double bonds in unsaturated fatty acids cis or trans?

Answer 3

Cis

Causes the fatty acid to bend at that position

Question 4

What do double-bonds do to the melting temp of a fatty acid?

Answer 4

addition of double bonds decreases the melting temperature of a fatty acid.

Question 5

What two fatty acids can only be obtained in diet and why are they important? Also, why can’t we make them?

Answer 5

Linoleic acid (the precursor of arachidonic acid that is the substrate for prostaglandin synthesis)

Linolenic acid (the precursor of other ω-3 fatty acids important for growth and development)

Human cells do not have the enzyme to introduce double bonds between carbon 9 and the methyl-group end.

Question 6

How to name a fatty acid

Answer 6

The carbon atoms are numbered beginning with the carboxyl carbon as carbon 1.
Ex. arachidonic acid is named as 20:4(5, 8, 11, 14). The number before the colon indicates the number of carbons in the chain, the number after the colon indicates the numbers of double bonds and those in the parentheses indicate the positions of double bonds.

Or:

Carbon atoms are numbered beginning with the second carbon as α , β, γ… the carbon of the terminal methyl group is called the ω-carbon regardless of chain length.

The double bonds in a fatty acid can also be counted beginning at the ω-end.

Question 7

Steps in fatty acid synthesis

Answer 7

1. Production of cytosolic Acetyl-CoA: Acetyl portion of Acetyl CoA condenses with OAA which produces citrate.
2. Citrate is then transported into the cytosol. Then it is lysed and turned back into Acetyl-CoA.
3. Mitochondrial acetyl CoA is produced by the oxidation of pyruvate, and by the catabolism of fatty acids, ketone bodies, and certain amino acids.
4. Conversion of Acetyl CoA to Malonyl CoA by Acetyl CoA Carboxylase. This is the RATE LIMITING STEP and is the commitment step and the major regulatory step as well.
5. Conversion of Malonyl CoA into palmitate by fatty acid synthase. This is a 4 step process that repeats and adds 2 carbons each time. Acetyl CoA is used for the first cycle; Malonyl CoA is used for subsequent cycles, ultimately forming palmitate.

Pyruvate (PDH) → Acetyl CoA (citrate synthase) → Citrate → Leaves mitochondria (ATP citrate lyase) → Cytosolic Acetyl CoA (Acetyl CoA Carboxylase) → Malonyl CoA (fatty acid synthase) → Palmitate → enters ER → can elongate or become desaturated → Triglycerides and lipids

Question 8

Important Functions of Fatty Acids

Answer 8

Major hydrophobic components of all cell membranes

Major storage form of metabolic energy: 70-80% of caloric reserve is triacylglycerols

Essential precursors for the eicosanoids (paracrine hormones: prostaglandins, leukotrienes, thromboxanes)

Question 9

Major Sources of Fatty Acids

Answer 9

Biosynthesis from small molecule intermediates derived from metabolic breakdown of sugars, amino acids and fats

Diet essential fatty acids (Linoleic and linolenic acid)

Question 10

What is the rate limiting step in fatty acid synthesis?

Answer 10

The formation of Malonyl CoA from Acetyl CoA by Acetyl CoA Carboxylase (ACC)

Question 11

Fatty acid elongation

Answer 11

Elongation of palmitate occurs in mitochondria and endoplasmic reticulum (ER)

A family of enzymes designated Fatty Acid Elongases catalyze the initial condensation step for elongation of saturated or polyunsaturated fatty acids.

Question 12

Fatty acid desaturation

Answer 12

Formation of a double bond in a fatty acid involves ER membrane proteins in mammalian cells, termed mixed-function oxidases.

Question 13

Diet influences on fatty acid synthesis

Answer 13

High carbohydrate leads to high pyruvate and acetyl CoA levels in the mitochondrion, which favors production and translocation of citrate from the mitochondrion to the cytosol, thus stimulating fatty acid synthesis.

High fat/low carbohydrate leads to low pyruvate flux in the mitochondrion. Fat metabolism is associated with elevated acyl CoA in the cytoplasm. Both conditions reduce fatty acid biosynthesis.

Question 14

Hormonal influence on fatty acid synthesis

Answer 14

High insulin favors fatty acid biosynthesis

High glucagon favors lipolysis (beta-oxidation) and decreased fatty acid biosynthesis.

Question 15

Hormonal influence on fatty acid synthesis

Answer 15

High insulin favors fatty acid biosynthesis

High glucagon favors lipolysis (beta-oxidation) and decreased fatty acid biosynthesis.

Question 16

Short-term regulators of fatty acid synthesis

Answer 16

Citrate: activator
Palmitoyl CoA: inhibitor
Insulin: activator
Glucagon: inhibitor

Question 17

Citrate effects on fatty acid synthesis

Answer 17

Availability of cytosolic citrate determines the amount of acetyl CoA available for fatty acid synthesis. It also helps produce NADPH for the reducing equivalents used in the reactions.

Citrate can also activate acetyl CoA carboxylase by causing polymerization of the enzyme (conformational change) and increasing the Vmax.

Question 18

Glucagon effects on fatty acid synthesis

Answer 18

Glucagon increases intracellular cAMP leading to phosphorylation and inactivation of acetyl CoA carboxylase.

Question 19

Triacylglycerols (TAGs)

Answer 19

TAGs are the major storage form of fatty acids.

Synthesis of TAG from glycerol 3-phosphate and fatty acyl CoA includes sequential addition of two fatty acids from fatty acyl CoA, then removal of the phosphate to add the third fatty acid.

The fatty acid on carbon 1 is typically saturated, on carbon 2 is typically unsaturated and on carbon 3 can be either.

Question 20

Triacylglycerols (TAGs)

Answer 20

TAGs are the major storage form of fatty acids.

Synthesis of TAG from glycerol 3-phosphate and fatty acyl CoA includes sequential addition of two fatty acids from fatty acyl CoA, then removal of the phosphate to add the third fatty acid.

The fatty acid on carbon 1 is typically saturated, on carbon 2 is typically unsaturated and on carbon 3 can be either.

TAGs synthesized in the liver are packaged with cholesteryl esters, cholesterol, phospholipids and apolipoprotein B-100 to form VLDL for delivery to the body.

Question 21

How does alcoholism lead to fatty liver?

Answer 21

Ethanol is metabolized to acetate, mainly in the liver, this rxn produces lots of NADH

Increased NADH/NAD+ slows TCA cycle and fatty acid oxidation, and promotes the formation of glycerol-3-P from DHAP

Glycerol-3-P + fatty acids → triacylglycerols

At first excess alcohol causes the liver to secrete abnormally high levels of VLDLs. However, chronic liver dysfunction impairs protein synthesis including Apo-B 100. Liver becomes unable to produce and secrete VLDL, increasing hepatic fat buildup.