Hepatic Metabolism Of Lipids

Question 1

What are some functions of the liver?

Answer 1

• Detoxification: Filters & cleans blood of waste products (drugs, hormones)
• Immune functions: Fights infections and diseases (RE system)
• Involved in Synthesis of clotting factors, proteins,
  enzymes, glycogen and fats
• Production of bile & breakdown of bilirubin
• Energy storage (glycogen and fats)
• Regulation of fat metabolism
• Ability to regenerate

Question 2

What is the metabolic role of the liver?

Answer 2

The liver maintains a continuous supply of energy for the body by controlling the metabolism of CHO and fats

Question 3

What is the liver regulated by?

Answer 3

• Endocrine glands eg pancreas, adrenal, thyroid
• Nerves

Question 4

What are lipids?

Answer 4

• Esters of fatty acids and glycerol or other compounds (cholesterol)
• Large and diverse group of naturally occurring organic compounds that are insoluble in water
• Variety of structure and functions

Question 5

What is a triglyceride?

Answer 5

1 glycerol molecule esterified to 3 fatty acids (bonded at carboxyl head)

Storage form of fat in our body
- Adipocytes
- Hepatocytes
- Elsewhere

Question 6

What is a saturated fatty acid?

Answer 6

• Lining up close together
• Their esters are solid at room temperature
• Their esters are: Solid “fats”

Question 7

What are unsaturated fatty acids?

Answer 7

• Needs more space
• Less tightly packed
• MUFA, PUFA
• Their esters are liquid at room temperature - “oils”

Question 8

What are the functions of lipids?

Answer 8

Energy reserve

Structural and other functions
- Part of cell membranes
- Integral to form and functions of cells
- Inflammatory cascades (LC-PUFAs precursors to eicosanoids e.g. prostaglandins)

Hormone metabolism
- Cholesterol is backbone of adrenocorticoid and sex hormones
- Vitamin D

Question 9

What is the main storage place for glycogen?

Answer 9

Liver

Question 10

What are lipids often transported as?

Answer 10

TGs or FAs bound to Albumin or within lipoproteins

• TGs cannot diffuse through cell membrane
• FA are released through lipases to facilitate transport into the cells
• In the cell FA are re-esterified to TG

Question 11

How is fatty acids uptook?

Answer 11

Diffusion through the lipid bilayer of the cell membrane

Facilitated transport
- Increases if increased substrate (↑supply) or increase in receptor molecules (↑ demand)
- Several transporter systems

FA binding protein (= mitochondrial AST) (induction to increased expression may result in increased uptake of FA in the hepatocytes)

FAT - fatty acid translocase
FATP - FA transport polypeptide

Question 12

What are lipoproteins?

Answer 12

Lipoproteins consists of a core containing TGs and cholesterol-esters and
a surface monolayer of phospholipids, cholesterol and specific protein
(e.g. Apoproteins)

Protein to lipid ratio varies

Question 13

What are lipoproteins defined by?

Answer 13

Their density (LDL, HDL, chylomicrons)

Question 14

What is the function of chylomicrons?

Answer 14

Carry lipids from the gut to muscle and adipose tissue

Question 15

What are chylomicron remnants taken up by?

Answer 15

By the liver via receptor mediated endocytosis

Question 16

What is cholesterol?

Answer 16

Cholesterol is esterified intracellular by acyl-CoA:cholesterol acyltransferase or by lecithin: cholesterol acyltransferase in lipoproteins

Question 17

What is the major organ in which cholesterol is processed?

Answer 17

Liver

Question 18

What is the export system of cholesterol?

Answer 18

Excretion of cholesterol through bile

Question 19

What do lipoproteins carry?

Answer 19

Lipoproteins carry TG and cholesterol through the circulatory system

Question 20

What are the 3 locations for oxidation in the liver?

Answer 20

Peroxysomal β-oxidation
Mitochondrial β-oxidation
ER Ω-oxidation (CYP4a catalysed)

Question 21

What is mitochondrial B-oxidation?

Answer 21

• Primarily involved in oxidation of FAs of various chain length
• Multistep process
• Progressive shortening into acetyl-CoA subunits
  Condensed into ketone bodies providing oxidisable energy to cells
  Enter tricarboxyl acid cycle – resulting in H2O and CO2

Question 22

What is mitochondrial B-oxidation regulated by?

Answer 22

Regulated by CPT (carnitine palmitosyl transferase), carnitine concentration and malonyl-CoA (which inhibits CPT)

Question 23

What is the main role of peroxisomal B-oxidation?

Answer 23

Main role is detoxification of
- very long chain fatty acids (>C 20)
- 2-methyl-branched FAs
- Dicarbolic acids – very toxic – inhibiting mitochondrial fatty acid oxidation
- Prostanoids
- C-27 bile acid intermediaries

• 4 step process is repeatedly performed to shorten chain length. Each step can be carried out by at least 2 enzymes
• Several enzyme are induced by PPARά
• Disruption leads to micro-vesicular steatosis

Question 24

What is Microsomal Ω -oxidation?

Answer 24

• Normally a minor metabolic pathway but in fat overload increases
• CYP4A enzymes oxidise saturated and unsaturated fatty acids
• Ω-hydroxylation in the ER, followed by decarboxylation of the Ω-hydroxy fatty acid in the cytosol – in turn enter the β-oxidation pathway
• Dicarboxyl FA act as ligands to PPARά – induction of the oxidation systems

Question 25

What do FAs regulate?

Answer 25

Regulate gene expression by controlling activity of key transcription factors (TF)

Question 26

What are the various functions of TFs?

Answer 26

• Integration of signals from diverse pathways
• Co-ordination of the metabolic machinery for FA metabolism