Fatty Acid Synthesis

Question 1

Fatty acid

Answer 1

• simplest form of lipids
• 16C chain with carboxylic acid; hydrophobic tail is very insoluble
• can have saturated (no double bonds) or unsaturated (double bonds) fatty acids

Question 2

Storage form of fatty acids

Answer 2

Rarely any FFAs, they are instead esterfied as triacylgylcerol (tryglycerides).

Closet forms to polymers because FFA cannot join end to end, but they can aggregate in large globules

Question 3

Where does most FA synthesis occur?

Answer 3

cytoplasm in the Liver

Question 4

Fatty Acid synthesis

Answer 4

Begins when nutrients are in excess.

1. Starting material is acetyl-CoA in the mitochondria
2. Acetyl-CoA + oxaloacetate = citrate; A citrate shuttle moves citrate into the cytoplasm
3. Citrate is returned back to oxaloacetate and acetyl-CoA
4. Acetyl-CoA +carboxybiotin makes malonyl-CoA (using acetyl-CoA carboxylase ACC)
5. Malonyl-CoA + Acetyl-CoA (+6x more malonyl-CoA) –> Palmitate Fatty Acid

Question 5

What nutrients can be used as a source to create acetyl-CoA?

Answer 5

Amino acids (glucogenic and ketogenic amino acids)

Carbohydrates (glucose)

Lipids (glycerol and fatty acids)

Question 6

Palmitate

Answer 6

The basic precursor for other fatty acids.

16C

Desaturase (adds double bonds)
Elongase (extend C chain)

Question 7

How is acetyl-CoA Carboxylase controlled?

Answer 7

• allosterically controlled, activated by citrate and inhibited by palmitoyl-CoA
• hormonally controlled, reversible phosphorylation (dephosphorylation=active). Increased insulin= dephosphorylation= FA synthesis
  Glucagon/epinephrine or high AMP causes phosphorylation = no FA synthesis

Question 8

Acetyl-CoA carboxylase

Answer 8

used to make malonyl-CoA

Question 9

Fatty Acid synthase

Answer 9

enzyme used to form FFAs

Question 10

Triglyceride formation

Answer 10

Glycerol-3-phosphate and 3 fatty acyl-CoA used to produce triglycerides

Question 11

Formation of glycerol-3-phosphate

Answer 11

Liver and Kidney: Phosphorylation of glycerol (by glycerol kinase) forms glycerol-3-phosphate

Adipose: Reduction of dihydroxyacetone phosphate from glycolysis forms glycerol-3-phosphate

Question 12

Where are fatty acids stored?

Answer 12

Stored in adipose tissue

Question 13

How are triglycerides transported for storage in the liver?

Answer 13

Triglycerides are insoluble and need to be put in lipoprotein complexes for transport in plasma between tissues. Lipoprotein lipase binds to apoproteins of lipoproteins to release the tryglycerides as FFAs.
FFAs bind to albumin in the blood which allows them to be transported inside tissues by CD36. Once inside must be reesterified into triglycerides.

Question 14

Classes of lipoproteins

Answer 14

• Chylomicrons (CM)- transports exogenous fat (from diet). They have the highest density of triglycerides
• Very Low density lipoproteins (VLDL)- transports endogenous fat (made by the body)
• Intermediate/low/high density lipoproteins (IDL, LDL, HDL)- breakdown products of VLDL and CM

Question 15

What activates LPL?

Answer 15

LPL is activated by insulin

Question 16

Can fat be used by the brain?

Answer 16

FFAs and albumin cannot pass through the blood brain barrier so cannot be used by the brain

Question 17

Insulin regulation of fatty acid metabolism

Answer 17

1. Activates ACC via dephosphorylation
2. Activate LPL to increase lipoprotein breakdown in plasma transports triglycerides into tissues
3. Activate GLUT 4 to promote glucose uptake in adipose which is required for re-esterified FFA’s into triglycerides

Question 18

Hyperlipidemias (excess lipids in blood)

Answer 18

• Elevated levels of triglycerides
• Results in Lactescent (milky) serum
• Observed after high fat diet, cloudiness due to elevated chylomicron (fat from diet). If persist after fasting, it is due to high levels of VLDL (endogenous fat)
• Common in miniature schnauzers (1/3 idiopathic); LPL deficiency reported in inherited hyperlipidemia of New Zealand cats

Question 19

What causes hyperlipidemia?

Answer 19

Caused by diabetes mellitus, hypothyroidism, or Cushing’s disease