Liver Physiology

Question 1

Lipid transport systems

Answer 1

Fatty acid binding protein (mitochondrial AST)
Fatty acid translocase (FAT)
Fatty acid transport polypeptide (FATP)

Question 2

Lipid functions

Answer 2

Detoxification - filters and cleans blood of waste
Immune functions
synthesis - clotting factors, proteins, enzymes, glycogen
Production of bile
Energy storage - mainly glycogen
Metabolic - regulation of blood glucose

Question 3

Insulin on lipids

Answer 3

Insulin stimulates breakdown of TG to FA acids - to store in adipocytes
Reduces activity of hormone sensitive lipase - leading to reduced FA export from adipocytes

Question 4

Insulin resistance and lipids

Answer 4

Increased lipolysis in adipocytes leading to increased TG in circulation
Increased offer of FA to hepatocytes leading to increased uptake
Increased glucose levels leads to less demand for lipids to be used as energy source

Question 5

Lipogenesis

Answer 5

Dependent on insulin concentration and sensitivity
Hepatic de novo lipogenesis (endogenous synthesis of fatty acids) is primarily for export in lipoproteins
Sequential extension of an alkanoic chain starting from Acetyl-CoA via serial decarboxylative condensation
Inactivated by catecholamines and glucagon

Question 6

Fatty acid export from the liver

Answer 6

Apoprotein B (ApoB) 100 synthesized by RER
Lipid components synthesized in SER
Added by microsomal TAG transfer protein to ApoB
Transported in vesicle to golgi body where ApoB is glycosylated (a carbohydrate is added to a functional group)
Then buds off golgi body
Vesicle fuse with the membranes and VLDL is released

Question 7

Fatty Acid Oxidation

Answer 7

Proportional to plasma levels of FFA released from adipodcytes
Peripheral FA mobilization - increased glucagon
3 locations of oxidation in liver - Mitochondrial B-oxidation, Peroxysomal B-oxidation and ER Ω-oxidation

Question 8

Peroxysomal B-oxidation

Answer 8

Main role is detoxification of - 
Very long chain fatty acids, 
2-methyl branched FA, 
dicarbolic acid, 
Prostanoids
C-27 bile acid intermediate
4 Step process repeatedly performed to shorten chain - can be carried put by at least 2 ezymes

Question 9

Steatosis

Answer 9

Abnormal retention of lipids

Question 10

Mitochondrial B-oxidation

Answer 10

Primarily involved in oxidation of FAs of various chain length
Progressive shortening into acetyl-CoA subunits
Condensed into ketone bodies providing oxidizable energy to cells
Enter tricarboxyl acid cycle
Resulting in H2O and CO2

Question 11

ER Ω-oxidation

Answer 11

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

Question 12

Fatty acids and regulation

Answer 12

FAs regulate gene expression by controlling activity of key transcription factors (TFs)
Peroxisome proliferator-activated receptors - PPARά,β, γ, δ
PPAR άβδ facilitate energy combustion
PPAR γ facilitates energy storage
PPAR ά is a lipid sensor – gene transcription - reduced activity leads to steatosis

Question 13

Liver storage

Answer 13

Iron
Glycogen
Vitamins - A, B12, C, D, E, Folate, K
Clotting factors - 1, 2, 4, 5, 6, 7 (produced in liver)

Question 14

Xenobiotic

Answer 14

A chemical substance found within an organism that is not naturally produced or expected to be present
May be toxic if not excreted in time
Act by damaging protein, DNA and lipids
Can react with oxygen to form free radicals
Kidneys can only excrete water soluble material so may need to be converted

Question 15

Metabolism of drugs in 2 phases

Answer 15

Phase 1 - To add a functional group to increase hydrophilicity
Reactions - oxidation, reduction and hyrdolysis

Phase 2 - conjugation
Reactions - glycoside conjugation, sulphination, glutathione, methylation, acylation, phosphate conjugation