7.3 Extrahepatic Macronutrient and Alcohol Metabolism

Extrahepatic Macronutrient Metabolism

Because the liver is so important in metabolism, the term extrahepatic has been defined to mean “located or occurring outside of the liver1”. We are next going to consider extrahepatic tissue metabolism.

Figure 7.31 The liver “is kind of a big deal2”

To start considering the metabolic capabilities of the extrahepatic tissues, we start by removing the following pathways that only or mostly occur in the liver:

• Alcohol oxidation
• Gluconeogenesis
• Ketone body synthesis
• Urea synthesis
• Lactate breakdown
• Glucose-6-phosphatase

These metabolic processes are crossed off in the Figure 7.32.

Figure 7.32 Removing the pathways that only or mostly occur in the liver3

We are left with metabolic capabilities that are listed and shown below.

• Glycogen synthesis and breakdown
• Glycolysis
• Fatty acid synthesis and breakdown
• Triglyceride synthesis and breakdown
• Protein synthesis and breakdown

Figure 7.33 The metabolic capability of the extrahepatic tissues3

We will use this figure as the base for metabolic capabilities of the different extrahepatic tissues to compare what pathways other tissues can perform versus all the pathways performed by extrahepatic tissues.

In an effort to keep this simple, we are going to focus on four extrahepatic tissues in the following subsections:

• 7.31 Muscle Macronutrient Metabolism
• 7.32 Adipose Macronutrient Metabolism
• 7.33 Brain Macronutrient Metabolism
• 7.34 Red Blood Cell Macronutrient Metabolism

References & Links

• http://www.cancer.gov/dictionary/?CdrID=44498
• http://commons.wikimedia.org/wiki/File:Liver.svg
• http://en.wikipedia.org/wiki/File:CellRespiration.svg

Muscle Macronutrient Metabolism

Compared to extrahepatic tissues as a whole, in muscle tissue the following pathways are not performed or are not important:

• Fatty acid synthesis
• Ketone body breakdown

These pathways are crossed out in the figure below.

Figure 7.311 The metabolic pathways that are not performed or important in muscle tissue, compared to extrahepatic tissues as a whole1

Removing those pathways, the following metabolic pathways make up muscle metabolic capability:

• Glycogen synthesis and breakdown
• Glycolysis
• Protein synthesis and breakdown
• Triglyceride synthesis and breakdown
• Fatty acid breakdown
• Lactate synthesis

Figure 7.312 Muscle metabolic capability1

Muscle is a major extrahepatic metabolic tissue. It is the only extrahepatic tissue with significant glycogen stores. However, unlike the liver, muscle tissue cannot secrete glucose after it is taken up (there is no glucose-6-phosphatase in muscle cells). Thus, you can think of muscle tissue as being selfish with glucose. It either uses it for itself initially or stores it for its later use.

References & Links

1. http://en.wikipedia.org/wiki/File:CellRespiration.svg

Adipose Macronutrient Metabolism

It probably does not surprise you that the major function of adipose tissue is to store energy as triglycerides. Compared to extrahepatic tissues as a whole, in adipose tissue the following pathways are not performed or are not important:

• Glycogen synthesis and breakdown
• Lactate synthesis
• Ketone body breakdown
• Fatty acid breakdown
• Protein synthesis and breakdown
• Citric acid cycle (very little is necessary since adipose tissue not an active tissue needing energy)

These pathways are crossed out in the figure below.

Figure 7.321 The metabolic pathways that are not performed or important in adipose tissue, compared to extrahepatic tissues as a whole are crossed out1

Removing those pathways, we are left with metabolic capabilities listed below and depicted in Figure 7.322:

• Glycolysis
• Fatty acid synthesis
• Triglyceride synthesis and breakdown

Figure 7.322 Adipose metabolic capability

Fatty acid synthesis only occurs in adipose tissue and the liver. In adipose tissue, fatty acids are synthesized and most will be esterified into triglycerides to be stored. In the liver, some fatty acids will be esterified into triglycerides to be stored, but most triglycerides will be incorporated into VLDL so that they can be used or stored by other tissues.

References & Links

1. http://en.wikipedia.org/wiki/File:CellRespiration.svg

Brain Macronutrient Metabolism

Fatty acid breakdown does not occur to any great extent in the brain because of the limited activity of one of the enzymes in this pathway1. Compared to the extrahepatic tissues as a whole, in the brain the following pathways are not performed or are not important:

• Glycogen synthesis and breakdown
• Lactate synthesis
• Fatty acid synthesis and breakdown
• Triglyceride synthesis and breakdown
• Protein synthesis and breakdown

These pathways are crossed out in Figure 7.331.

Figure 7.331 The metabolic pathways that are not performed or important in the brain compared to extrahepatic tissues as a whole are crossed out2

Fatty acid breakdown does not occur to any great extent in the brain because low activity of an enzyme in the beta-oxidation pathway limits the activity of this pathway2.

By removing those pathways the only pathways left in the brain are:

• Glycolysis
• Ketone body breakdown

Figure 7.332 Brain metabolic capability1

Thus, due to its limited metabolic capabilities, the brain needs to receive either glucose or ketone bodies to use as an energy source.

References & Links

• Yang SY, He XY, Schulz H (1987) Fatty acid oxidation in rat brain is limited by the low activity of 3-ketoacyl- coenzyme A thiolase. J BIol Chem 262 (27): 13027-13032.
• http://en.wikipedia.org/wiki/File:CellRespiration.svg

Red Blood Cell Macronutrient Metabolism

Red blood cells are the most limited of the extrahepatic tissues because they do not contain a nucleus or other cell organelles, most notably mitochondria.

Figure 7.341 Red blood cells do not contain mitochondria1

As a result, compared to the extrahepatic tissues, in red blood cells the following pathways are not performed or are not important:

• Glycogen synthesis and breakdown
• Lactate breakdown
• Fatty acid synthesis and breakdown
• Triglyceride synthesis and breakdown
• Protein synthesis and breakdown
• Ketone body breakdown

These pathways are crossed off in Figure 7.342.

Figure 7.342 The metabolic pathways that are not performed or important in the red blood cells, compared to extrahepatic tissues as a whole are crossed off2

If all those pathways are removed, only glycolysis is left, where pyruvate is ultimately, converted to lactate.

Figure 7.343 Red blood cell metabolic capability

Thus, red blood cells are one-trick ponies, only being able to perform glycolysis and produce lactate.

Figure 7.344 Red blood cells are one-trick ponies

References & Links

• http://en.wikipedia.org/wiki/Mitochondrion
• http://en.wikipedia.org/wiki/File:CellRespiration.svg