The Liver
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Introduction
The liver is the largest and most diverse internal organ. It plays a central role in many essential physiologic processes, such as glucose homeostasis, plasma protein synthesis, lipid and lipoprotein synthesis, bile acid synthesis and secretion, and storage of vitamins B12, A, D, E, and K. The liver is also vital in biotransformation, detoxification, and excretion of many endogenous and exogenous compounds. Regulates blood clotting.
The liver is located on the right side of the body under the lower ribcage. It is connected to the gallbladder. Blood carrying contents of the stomach and intestines flows directly to the liver.
Monitors countless other proteins.
Anatomy
External resource: Virtual liver
Liver is logically organized around a central vein.
If it is the metabolites that damage, central liver will be damaged as toxic metabolites flow. Conversely, a direct toxin such as copper will damage everywhere.
All you need is 1/4 of a liver to survive.
Function
Liver and Metabolism
The liver is uniquely situated to process and distribute dietary nutrients because blood leaving the pancreas and gut enter the liver before traveling to the rest of the body. After a meal, the liver receives blood high in nutrients and metabolizes, stores, and secretes important macromolecules for use by other tissues. In this way, the liver acts as a gatekeeper/storehouse something else. The primary role of the liver during the fasting state is the synthesis and distribution of fuel sources for the tissues of the body.
<<img of liver receiving input from the gut and pancreas and sending it on its way. >>
- carbohydrate metabolism
- lipid metabolism
- amino acid metabolism
Carbohydrate Metabolism
The liver is normally a glucose-producing organ. However, after a meal, the liver consumes roughly 60% of glucose through elevation of the following mechanisms:
- Glucokinase becomes activated by high levels of glucose, producing glucose 6-phosphate.
- Glycogen synthase becomes activated
- Increased glucose 6-P levels activates the pentose phosphate pathway in order to generate NADPH for use in lipogenesis
- An elevated insulin/glucagon ratio activates glycolysis through regulation of PFK-1
- Gluconeogensis is inhibited by a high insulin:glucagon ratio
fasting state
- Glycogen degradation occurs following a decrease in the insulin:glucagon ratio several hours after a meal. Glycogen levels in the liver are exhausted 10-18 h after fasting
- Increased gluconeogenesis occurs, with carbon skeletons derived primarily from amino acids, glycerol, and lactate
Role in Lipid Metabolism
- Bile synthesis and secretion (from the gall bladder) aids in lipid digestion
- Increased fatty acid synthesis, favored by the availability of Acetyl CoA and NADPH.
- Increased TAG synthesis from FA's and glycerol 3-phosphate from glycolysis
- increased packaging and secretion of VLDLs
fasting state
- Increased fatty acid oxidation from liberated FFAs from adipose tissue
- Increased synthesis and secretion of ketone bodies following FA oxidation, reducing the need for amino acid degradation for gluconeogenesis
Role in Amino Acid Metabolism
- Increased protein synthesis to replace those lost since the last absorptive period
- Increased amino acid degradation, as the liver does not store surplus amino acids
Cell Biology
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Resources and References
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