POST Gluconeogenesis and the Urea Cycle

Transamination Reactions

• Transamination reactions transfer the nitrogen group from one molecule to another. This allows tissues to use the leftover carbon skeleton for other uses such as energy metabolism.

• This process also allows cells to produce some non-essential amino acids.

• Alpha ketoglutarate and glutamate are the most common acceptors of amino groups

• PLP, pyridoxal phosphate, is the coenzyme required for transamination. PLP is the active form of the vitamin B6.

Deamination

• Deamination removes a nitrogen from a molecule, but generates nitrogenous waste (NH3/NH4+)

• Deamination still allows cells to use the carbon skeleton of amino acids for energy.

• Because NH3 and NH4+ are toxic, the body deals with excess NH4+ by letting it bind to alpha ketoglutarate (making it turn into glutamate). However, if there is way too much NH4+, the cell will use up the entire store of alpha ketoglutarate. This is bad because alpha ketoglutarate is an intermediate in the Krebs cycle, and if we use all of it, the TCA cycle will no longer function, leading to a lack of energy in that cell.

How Does Ammonium Travel in The Blood to Be Excreted?

• To be transported safely to the kidneys, where it can be excreted via urine, nitrogen is transported through polar molecules in a non-toxic way

  • It travels as the amino acids glutamine and alanine

  • It travels as urea

Elevated Ammonia Levels Point to? Elevated Urea?

• A healthy liver can efficiently produce urea. The greater the amount of ammonium produced, the greater the urea production

• A healthy kidney can efficiently remove urea.

• Too much ammonium in the blood points to liver issues, while too much urea in the blood points to kidney issues.

Alanine

• Alanine is non-toxic and polar, meaning it can freely travel in the blood

• Tissues can release excess nitrogen as alanine. From there, the blood can take it to the liver.

• In the liver, alanine undergoes transamination, converting it to pyruvate and transferring the N to glutamate (alpha ketoglutarate turns into glutamate).

• Pyruvate can be used for energy (by making it Acetyl CoA to go into the TCA cycle), or converted back into glucose

• Glutamate can be deaminated to regenerate alpha ketoglutarate. The NH4+ that is released can be transferred to Urea.

The Urea Cycle

• The urea cycle is a multi-step cycle that takes place in the liver. If the liver can’t make urea, nitrogen will build up in the blood.

Gluconeogenesis

• During fasting, the liver produces glucose to maintain blood glucose levels

• The liver stores of glycolysis are exhausted before creating new glucose

• Gluconeogenesis is the use of non-carb sources to produce glucose

• Pyruvate is produced in the liver from gluconeogenic precursors which include lactate, glycerol and amino acids.