6.4 Protein Metabolsim

6.4 Protein Metabolism

Section 2.22 described how proteins are synthesized. Thus, this section will focus on how proteins and amino acids are broken down. There are four protein metabolic pathways that will be covered in this section:

Transamination – transfer of an amino group from one amino acid to another

Deamination – removal of an amino group, normally from an amino acid. Gluconeogenesis – synthesis of glucose from a non-carbohydrate source. Protein Turnover/Degradation – liberation of amino acids from proteins.

Subsections:

• Transamination, Deamination, & Ammonia Removal as Urea
• Gluconeogenesis
• Protein Turnover/Degradation

Transamination, Deamination & Ammonia Removal as Urea

Amino acids are important metabolic resources for our cells. The first step in making an amino acid useful is deamination, the removal of its amino group (-NH₂). Once the amino group has been removed, what remains is a 2-carbon keto acid with a side chain. The keto acid is the valuable component of the amino acid in that it can be used as a foundation for the construction of a new amino acid (transamination below), it can be used as the foundation for the construction of ketone bodies (ketogenesis below), and it can be used as a starting point for the construction of glucose (gluconeogenesis below). As we shall see below, not all amino acids are the same in terms of what can be done with them after an event of deamination. We will also determine that deamination has a possible negative consequence (hyperammonemia).

Transamination

Transamination is the transfer of an amino group from an amino acid to a keto acid (amino acid without an amino group), thus creating a new amino acid and keto acid as shown below.

Figure 6.411 Generic transamination reaction where the top keto acid is converted to an amino acid, while the bottom amino acid is converted to a keto acid1

Keto acids and/or carbon skeletons are what remains after amino acids have had their nitrogen group removed by deamination or transamination. Transamination is used to synthesize nonessential amino acids.

Deamination

Deamination is the removal of the amino group as ammonia (NH₃), as shown below.

Figure 6.412 Deamination of cytosine to uracil (nucleotides, not amino acids)2

The potential problem with deamination is that too much ammonia is toxic, causing a condition known as hyperammonemia. The symptoms of this condition are shown in the following figure.

Figure 6.413 Symptoms of Hyperammonemia3

Our body has a method to safely package ammonia in a less toxic form to be excreted. This safer compound is urea, which is produced by the liver using 2 molecules of ammonia (NH₃) and 1 molecule of carbon dioxide (CO₂). Most urea is then secreted from the liver and incorporated into urine in the kidney to be excreted from the body, as shown in Figure 6.414.

Figure 6.414 Production of urea helps to safely remove ammonia from the body4-6

References

• http://en.wikipedia.org/wiki/File:Transaminierung.svg
• http://en.wikipedia.org/wiki/File:DesaminierungCtoU.png
• http://en.wikipedia.org/wiki/File:Symptoms_of_hyperammonemia.svg
• http://commons.wikimedia.org/wiki/File:Liver.svg
• http://upload.wikimedia.org/wikipedia/commons/b/b0/Kidney_section.jpg
• http://en.wikipedia.org/wiki/File:Urea.png

Gluconeogenesis

Gluconeogenesis is the synthesis of glucose from non-carbohydrate sources. Certain amino acids can be used for this process, which is the reason that this section is included here instead of the carbohydrate metabolism section. Gluconeogenesis is glycolysis in reverse with an oxaloacetate workaround, as shown below. Remember oxaloacetate is also an intermediate in the citric acid cycle.

Figure 6.421 Gluconeogenesis is glycolysis in reverse with an oxaloacetate workaround1

Not all amino acids can be used for gluconeogenesis. The ones that can be used are termed glucogenic, and can be converted to either pyruvate or a citric acid cycle intermediate. Other amino acids can only be converted to either acetyl-CoA or acetoacetyl-CoA, which cannot be used for gluconeogenesis. However, acetyl-CoA or acetoacetyl-CoA can be used for ketogenesis to synthesize the ketone bodies, acetone and acetoacetate. Thus, these amino acids are instead termed ketogenic.

In addition to ketogenic amino acids, fatty acids also cannot be used to synthesize glucose. The transition reaction is a one-way reaction, meaning that acetyl-CoA cannot be converted back to pyruvate. As a result, fatty acids can’t be used to synthesize glucose, because their oxidation produces acetyl-CoA. This acetyl-CoA enters the citric acid cycle and the carbons from it will eventually be completely oxidized and given off as CO₂. It is important to remember that while the fatty acids from a triglyceride cannot be used to generate glucose, that the glycerol portion of the triglyceride (Figure 6.315).

References

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

Protein Turnover/Degradation

Proteins serve a number of functions in the body, but what happens they have completed their lifespan? They are recycled.

Figure 6.431 Recycling symbol1

Proteins are broken down to amino acids that can be used to synthesize new proteins. Two of the main systems of protein degradation are:

• Ubiquitin-proteasome degradation
• Lysosome degradation

Ubiquitin-Proteasome Degradation

Proteins that are damaged or abnormal are tagged with the protein ubiquitin. There are multiple protein subunits involved in the process (E1-E3), but the net result is the production of a protein (substrate) with a ubiquitin tail, as shown below.

Figure 6.432 Ubiquitination of a protein (substrate)2

This protein then moves to the proteasome for degradation. Think of the proteasome like a garbage disposal. The ubiquitinated “trash” protein is inserted into the garbage disposal where it is broken down into its component parts (primarily amino acids). The following video illustrates this process nicely.

Web LinkVideo: Proteasome Degradation (0:44)

Lysosome Degradation

The lysosomes are organelles that are found in cells. They contain a number of proteases (enzymes that breakdown proteins) that degrade proteins, similar to how proteins are digested in our own GI tracts.

References & Links

• http://en.wikipedia.org/wiki/File:Recycling_symbol.svg
• http://en.wikipedia.org/wiki/File:Ubiquitylation.svg
• http://en.wikipedia.org/wiki/File:Illu_cell_structure.jpg

Video

Proteasome Degradation – https://www.youtube.com/watch?v=w2Qd6v-4IIc