Hepatic Metabolism Of Lipids Flashcards
What are some functions of the liver?
- 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
What is the metabolic role of the liver?
The liver maintains a continuous supply of energy for the body by controlling the metabolism of CHO and fats
What is the liver regulated by?
- Endocrine glands eg pancreas, adrenal, thyroid
- Nerves
What are lipids?
- 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
What is a triglyceride?
1 glycerol molecule esterified to 3 fatty acids (bonded at carboxyl head)
Storage form of fat in our body
- Adipocytes
- Hepatocytes
- Elsewhere
What is a saturated fatty acid?
- Lining up close together
- Their esters are solid at room temperature
- Their esters are: Solid “fats”
What are unsaturated fatty acids?
- Needs more space
- Less tightly packed
- MUFA, PUFA
- Their esters are liquid at room temperature - “oils”
What are the functions of lipids?
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
What is the main storage place for glycogen?
Liver
What are lipids often transported as?
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
How is fatty acids uptook?
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
What are lipoproteins?
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
What are lipoproteins defined by?
Their density (LDL, HDL, chylomicrons)
What is the function of chylomicrons?
Carry lipids from the gut to muscle and adipose tissue
What are chylomicron remnants taken up by?
By the liver via receptor mediated endocytosis
What is cholesterol?
Cholesterol is esterified intracellular by acyl-CoA:cholesterol acyltransferase or by lecithin: cholesterol acyltransferase in lipoproteins
What is the major organ in which cholesterol is processed?
Liver
What is the export system of cholesterol?
Excretion of cholesterol through bile
What do lipoproteins carry?
Lipoproteins carry TG and cholesterol through the circulatory system
What are the 3 locations for oxidation in the liver?
Peroxysomal β-oxidation
Mitochondrial β-oxidation
ER Ω-oxidation (CYP4a catalysed)
What is mitochondrial B-oxidation?
- 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
What is mitochondrial B-oxidation regulated by?
Regulated by CPT (carnitine palmitosyl transferase), carnitine concentration and malonyl-CoA (which inhibits CPT)
What is the main role of peroxisomal B-oxidation?
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
What is Microsomal Ω -oxidation?
- 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
