Liver metabolism

[deleted783484]

Why does the liver use dietary amino acids in the well-fed state to produce energy and fatty acids in the fasting mode? I would think that both amino acids and fatty acids would be used in a well-fed state because if we ate food that is rich in fat it passes through the portal vein and can be used by the liver for metabolism and the amino acids of proteins we eat can be used for metabolism as well.

Why would the liver not use ketone bodies to produce energy in the fasting state? It is for the same reason as glucose ? (because it needs to store it for other tissues that need it like the brain)

Thanks a lot

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[yeasureyoubetcha]

Why does the liver use dietary amino acids in the well-fed state to produce energy and fatty acids in the fasting mode?

There is always some basal level of AA metabolism going on in hepatocytes. However during the fed state, AA's are being absorbed. Insulin will stimulate protein synthesis in cells and cellular protein the main source of storage for AA's. During the fasting state, muscle and fat is broken down to provide transaminases with AA's, and the cell with glycerol heads for GNG precursors. The FA tails provide the energy for the hepatic GNG. The main energy source during the fed state is glucose.

I would think that both amino acids and fatty acids would be used in a well-fed state because if we ate food that is rich in fat it passes through the portal vein and can be used by the liver for metabolism and the amino acids of proteins we eat can be used for metabolism as well.

Absorbed dietary fats do not go through the portal vein to the liver. Most of our fats are long chain fatty acids. Short and medium chain FAs are released into the blood. Long chain FA's are packaged into TG's and chylomicrons and bypass the liver using the lacteals of the lymphatic system. They exit thoracic duct at the juncture btwn the left subclavian vein and left internal jugular for transport to the periphery going through systemic circulation before they hit the liver for the first time. This prevents fatty deposit accumulation in the liver.

Why would the liver not use ketone bodies to produce energy in the fasting state? It is for the same reason as glucose ? (because it needs to store it for other tissues that need it like the brain)

The liver doesn't use ketone bodies in the fasting state because it is missing the enzyme Acetoacetate succinyl-CoA transferase, but it does produce ketone bodies. Muscles and other cells that utilize ketone bodies have this enzyme. In fasting the liver gets its energy equivalents from beta-oxidation. Once the energy requirements of the hepatocytes is satisfied there is a high mitochondrial [NADH], TCA is slowed/inhibited and the acetyl-coA groups from beta-ox get shunted to ketogenesis. The liver does not want to use what is creating for the rest of the body to use--ketones, glucose.

 

[deleted783484]

There is always some basal level of AA metabolism going on in hepatocytes. However during the fed state, AA's are being absorbed. Insulin will stimulate protein synthesis in cells and cellular protein the main source of storage for AA's. During the fasting state, muscle and fat is broken down to provide transaminases with AA's, and the cell with glycerol heads for GNG precursors. The FA tails provide the energy for the hepatic GNG. The main energy source during the fed state is glucose.

Thank you so much for taking the time to write this! it helped a lot!

Regarding the reason the liver uses amino acid in a well fed state and fatty acids in a fasting state, can we consider that tissues use the other resources available as a primary source and will use fats as a secondary source if no primary source is available such as glucose or a.a for degradation?

 

[yeasureyoubetcha]

Thank you so much for taking the time to write this! it helped a lot!

Regarding the reason the liver uses amino acid in a well fed state and fatty acids in a fasting state, can we consider that tissues use the other resources available as a primary source and will use fats as a secondary source if no primary source is available such as glucose or a.a for degradation?

I'm not sure about the AA use in the fed state. Its possible excess dietary AAs just get transaminated to pyruvate. Just focus on glucose for the MCAT though for the fed state. Different tissues are able to use different energy sources:

Brain: Glucose + ketones
RBCs: Glucose only
Muscle: Glucose, Ketone, fatty acids, some amino acids, fructose
Hepatocytes: Glucose, FA, AA, lactate, fructose, galactose, ethanol