Fatty Acid Biosynthesis

Question 1

Where is majority of required fatty acids supplied in ?

Answer 1

Diet

Question 2

Where is the pathway present ?

Answer 2

In liver, brain, kidney, mammary gland and adipose tissue for de novo synthesis from 2-carbon compounds

Question 3

When is the pathway used ?

Answer 3

In conditions of excess energy in particular carbohydrate intake

Question 4

What is converted fatty acids stored as ?

Answer 4

Triaclyglycerols

Question 5

What is the 2 stage process in the pathway ?

Answer 5

Preparation of precursor malonyl-CoA and elongation of fatty acid

Question 6

Fatty acid synthesis occurs in ?

Answer 6

The cytosol, consistent with being a reductive process

Question 7

Since fatty acid synthesis occurs in the cytosol, acetyl coA needs to ?

Answer 7

Be shuttled out of the mitochondria

Question 8

What allows acetyl coA to cross the mito membrane?

Answer 8

Citrate can interact with a carrier

Question 9

What does fatty acid synthesis require ?

Answer 9

Both stages require:
Acetyl-CoA and multienzyme complex

1. Preparation of malonyl-CoA by acetyl CoA carboxylase
2. Elongation of FA chain by fatty acid synthase

Question 10

Explain Acetyl-CoA carboxylase ?

Answer 10

• Acetyl-CoA converted to malonyl CoA
• Biotin dependent enzyme
• Its subunits serve as
  1. biotin carboxylase,
  2. transcarboxylase
  3. biotin-carboxyl carrier protein
• Enzyme synthesised as inactive protomer – regulated by citrate and palmitoyl-CoA
• Reaction occurs in two stages
  1. Carboxylation of biotin (+ ATP)
  2. Transfer of carboxyl group to acetyl-CoA
• Carboxylation of acetyl CoA is first committed step of FA synthesis

Question 11

Acetyl-CoA carboxylase is regulated ?

Answer 11

By phosphorylation

Question 12

What does the cytosolic pathway lead to ?

Answer 12

To the synthesis of saturated fatty acids, with the main product being the 16 carbon fatty acid palmitate

Question 13

Elongation reactions are catalysed by ?

Answer 13

Enzymes located on the cytosolic face of the endoplasmic reticulum membrane. Malonyl CoA acts as the donor

Question 14

Reduction reactions also occur at ?

Answer 14

The ER membrane to produce unsaturated fatty acids

Question 15

Explain Fatty acid elongation ?

Answer 15

• FA elongation occurs on ER
• Requires fatty acid elongase
• Again occurs by addition of malonyl CoA
• Similar reactions to FA synthase except FA attached to CoA rather than ACP

Question 16

Very long chain FA produced in brain which increases ?

Answer 16

Rapidly during myelination producing the FA required for sphingolipid production

Question 17

In both liver and adipose tissue, TAGS produced by a ?

Answer 17

Pathway involving glycerol-3-phosphate

Question 18

The origin is dependent on the tissue ?

Answer 18

• In liver - glycerol
• In adipose tissue - glucose
• In both - intermediates are G-3-P & Phosphatidic acid

Question 19

Explain Cholesterol ?

Answer 19

• Mol wt 386 kDa
• almost completely saturated – only 1 double bond
• Low solubility in water
• Precursor of bile acids, steroid hormones and vitamin D
• Typical diet contains 500mg daily, 30-60% of this absorbed from gut
• Humans synthesise 1g daily
• Only 30% in free form, majority esterified to long chain fatty acids

Question 20

All human cells have ability to make cholesterol. Where is the major site of synthesis ?

Answer 20

The liver

Question 21

What does 1 cholesterol require ?

Answer 21

• 18 acetyl CoA
• 36 ATP
• 16 NADPH

Question 22

What is the unique starting compound in this pathway?

Answer 22

Mevalonic Acid

Question 23

Producing Cholesterol ?

Answer 23

• HMG-CoA reductase enables the cell to make cholesterol

- Cholesterol is released into the blood

Question 24

Limiting Cholesterol production ?

Answer 24

• Cholesterol-lowering statin drugs work by inhibiting HMG-CoA reductase
• Cholesterol production is blocked, lowering levels of cholesterol in the blood

Question 25

Adipose tissue are ?

Answer 25

Hormonally active

Question 26

Adipokines (leptin, adiponectin, resistin, growth factors and inflammatory cytokines generated by ?

Answer 26

Adipocytes

Question 27

What are the main adiposity signals ?

Answer 27

Leptin and insulin (synthesised by pancreas)

Question 28

Amount of leptin proportional to ?

Answer 28

Body fat content

Question 29

Leptin decreases ?

Answer 29

Appetite and increase thermogenesis

Question 30

After a moderate-high carbohydrate meal, fatty acid oxidation in liver is ?

Answer 30

Suppressed and synthesis is promoted

Question 31

During starvation fatty oxidation in liver is ?

Answer 31

Stimulated and fatty acid synthesis is suppressed

Question 32

Increased blood flow to muscles due to ?

Answer 32

Local mediators and β-adrenergic stimulation of

vascular smooth muscles

Question 33

Glycogen breakdown and some steps in glycolysis are greatly stimulated by ?

Answer 33

Stress