Lipid Synthesis + Degradation

Question 1

Fats play essential role in many biological functions including

Answer 1

Membranes
uptake of lipid soluble vitamins
As precursors of steroid hormones
Energy store

Question 2

What is major site of fatty acid synthesis?

Answer 2

Liver

Question 3

Where is fat stored?

Answer 3

In adipose tissue

Question 4

What are initial products of fatty acid synthesis?

Answer 4

Palmitric acid, oleic acid

Question 5

Describe the structure of fatty acid?

Answer 5

Chains of methyl groups
Terminal carbonyl group
Double bonds if present are usually in cis conformation

Question 6

Where does fatty acid synthesis takes place and what does it require?

Answer 6

Takes place in cytosol

Requires acetyl coA, NADPH

Question 7

What is first step in fatty acid synthesis?

Answer 7

Acetyl coA (2C) + ATP + HCO3 -> Malonyl coA(3C) + ACP + Pi

Question 8

What is enzyme involved in first of fatty acid synthesis?

Answer 8

Acetyl coA carboxylase

Question 9

What inhibits acetyl coA carboxylase?

Answer 9

Phosphorylation

Question 10

What stimulates phosphorylation in the 1st step of fatty acid?

Answer 10

Glucagon

This phosphorylation inhibits acetyl coA carboxylase

Question 11

Expression of acetyl coA carboxylase is increased by…… and decreased by…….

Answer 11

Increased by high carbohydrate + low fat

Decreased by low carbohydrate + high fat

Question 12

What activates the first step of fatty acid synthesis?

Answer 12

Activated by Citrate (+ve feedback)

Question 13

What inhibits the first step of fatty acid synthesis?

Answer 13

Inhibited by palmitic acid (-ve feedback)

Question 14

What is second step of fatty acid synthesis and what takes place?

Answer 14

Elongation
Reaction with ACP 
Cytosolic 
Addition of 2 carbons 
Acetyl coA + malonyl coA are activated by combination with ACP
Process does require NADPH

Question 15

What is enzyme involved in fatty acid synthesis and describe its structure?

Answer 15

Fatty acid acid synthase
It exists as dimer which makes the fatty acid synthesis the most efficient it can be
Structured nose to tail therefore you get continual movement from reactants to products
Having multi complex enzymes means that all required components for synthesis are in right place at right time

Question 16

Describe the structure of cholesterol?

Answer 16

Rigid hydrophobic molecule virtually insoluble in water
Precursor of sterols, steroids + bile salts
Transported in circulation as cholesteryl esters
Cannot be oxidised o oxygen + water so provides no energy
Important membrane components

Question 17

Describe the cholesterol synthesis?

Answer 17

Synthesised mostly in ER
Over 30 steps involved
Starts with activation of acetate + acetyl coA
Major regulatory step => conversion of 3 hydroxyl 3 methylglutaryl coA (HMGcoA) to mevalonate
Cholesterol inhibits HMGCoA reductase, the enzyme is involved in its own synthesis

Question 18

What are 3 stages of fatty acid degradation?

What does these stages take place?

Answer 18

Mobilisation- adipocyte
Activation - liver cytosol
Degradation - liver mitochondria

Question 19

Describe what takes place in mobilisation?

Answer 19

cAMP mediated response
cAMP activates protein kinase A
In adipocytes, this activation of protein kinase A leads to activation of triacylglycerol lipase= enzyme which when phosphorylated will remove + start break down triglycerides.
Triglycerides are broken down into fatty acids + cholesterol which are either used locally or transported back to liver

Question 20

When is mobilisation important?

Answer 20

When food is not readily available for example starvation or exercise stimulated by glucagon + Adrenalin but inhibited by insulin

Question 21

What is fate of glycerol?

Answer 21

Absorbed by liver
Small amount of glycerol can be used in glycolysis
Majority of glycerol will undergo gluconeogenesis

Question 22

Describe what takes place in activation?

Answer 22

Long chain fatty acid is activated by reaction with CoA to give acyl-coA—ATP in outer mitochondrial membrane
Transported to inner mitochondrial matrix for oxidation using carnitine. The transporter used is translocase
Transport is inhibited by malonyl coA

Question 23

Deficiency in alcohol carnitine leads to…

Answer 23

Muscle weakness or even death

Question 24

Describe what happens in fatty acid oxidation?

Answer 24

Takes place in liver mitochondria
Acyl-coA degraded by sequential removal of 2 carbon units
As result FADH2, NADH and acetyl coA are produced

Question 25

What takes place in fatty acid oxidation (B oxidation)?

Answer 25

FADH2 + NADH form ATP
Acetyl coA will enter citric acid cycle in presence of glycolysis
Complete oxidation of palmitate yields 106 molecules of ATP
Odd chain length yield propionyl-coA in last round of oxidation
Odd numbered double bonds are removed by isomerase even double bonds by reductase + isomerase

Question 26

What takes place in ketogenesis?

Answer 26

Acetyl coA converted to acetoacetyl coA
Acetoacetyl coA converted to HMG-coA
HMG-coA converted to acetoacetate
Acetoacetate can be reduced to 3 B-hydroxybuterate or non enzymatically to acetone

Question 27

Synthesis of ketone bodies are regulated by….

Answer 27

Insulin/glucagon ratio

Ketogenesis is high when ratio is low as this inhibits acetyl coA carboxylase

Question 28

What is fate of ketone bodies?

Answer 28

Major energy source for cardiac muscle + renal cortex=> dependent on flow of carbohydrates in glycolysis
During starvation up to 75% of brains energy derived from acetoacetate
Ketone bodies are converted back into acetyl coA
This acetyl coA in non-hepatic tissues will enter TCA cycle + will be used those cells for oxidative phosphorylation + generation of ATP

Question 29

Hormone regulation of fat metabolism

Answer 29

Insulin 
Increase in:
Glycolysis in liver 
Fatty acid synthesis in liver 
Triglycerides in adipose tissue 
B oxidation

Glucagon + Adrenalin
Increase in triglycerides + metabolism