Highlights Nitrogen Metabolism

1. Reduction of nitrogen to a form useful for organisms (called nitrogen fixation) is a difficult and energetically costly process. Nitrogen fixation is made possible by bacteria that have an enzyme known as the nitrogenase complex.

2. In nitrogen fixation, N2 is reduced to ammonium ion (NH4+). The process theoretically requires six electrons and 12 ATPs to make two ammonia molecules (NH3), but hydrogen gas is always produced, so two additional electrons and 4ATPs are also needed (giving a total of 8 electrons and 16 ATPs) .

3. Once reduced to ammonium ion, nitrogen can readily be incorporated into the amino acids glutamate, and glutamine.

4. Amino acids are grouped into families corresponding to the precursors they are made from. You should know the amino acids that are simple transamination products - glutamate (made from alpha-ketoglutarate), glutamine (made from glutamate), aspartate (made from oxaloacetate), alanine (made from pyruvate), asparagine (made from aspartate).

5. Transamination reactions are catalyzed by enzyme that use pyridoxal phosphate as a coenzyme. As a class, they are called 'transaminases.' Note that transamination reactions require an amine donor and an amine recipient (equivalent to reduction/oxidation reactions that require electron donors and recipients).

6. Folates are molecules that can donate single carbons to metabolic processes. (I mistakenly said in class they are involved in making FAD. That is NOT correct. FLAVINs are involved in making FAD. My brain was on vacation). Humans require folates in their diet and do not synthesize them from scratch. Bacteria, on the other hand, make them from scratch. An intermediate they use in this regard is para-amino-benzoic acid (PABA). Folates exist in two main forms for our purposes - dihydrofolates and tetrahydrofolates.

7. Anticancer drugs and antibiotics sometimes target folates. Bacterial cells start synthesis of folates with para-amino benzoic acid and drugs that mimic this are the sulfa drugs. Humans get folate in their diet, so we are not susceptible to action of these drugs. Methotrexate is an anti-cancer drug that mimics folate.

8. Another molecule inolved in single carbon reactions is known as S-Adenosyl-Methionine (SAM). It serves as a donor of methyl groups. After SAM donates its methyl group, it forms S-Adenylhomocysteine (SAH) that can be readily broken down to homocysteine. Elevated levels of homocysteine in the blood are associated with atherosclerosis. Reduction of homocysteine in the blood is accomplished with supplements of folic acid and, to a lesser extent, vitamins B6 and B12.

9. Essential amino acids for an organism are those amino acids that the organism cannot synthesize themselves and must be in their diet. Humans have 10 amino acids considered essential.

10. Breakdown of amino acids (catabolism) is divided into those amino acids whose carbon backbone forms intermediates in ketone body formation ( acetoacetyl-CoA and acetyl-CoA = ketogenic - Note - in class, I incorrectly called ketogenic acids as those going through the citric acid cycle. Though acetyl-CoA can go through the citric acid cycle, going through the cycle is not the definition of ketogenic. The correct definition is above), or glucose metabolism (oxaloacetate or pyruvate = glucogenic), or both.

11. The Urea Cycle is involved in nitrogen metabolism in cells. Note how an amine group of aspartate is transferred to form urea. You are not responsible for the individual reactions of the Urea Cycle, but should be aware of the molecules of the pathway that are amino acids or citric acid cycle intermediates, as well as the pathway's involvement in making urea by splitting it off of arginine. Note also that the cycle occurs partly in the mitochondria and partly in the cytoplasm.

12. Uric acid and urea are excretory forms of nitrogen. Human primarily excrete urea, whereas birds (and dalmations) excrete uric acid. Uric acid, which is a breakdown product of guanine, is NOT very soluble in water and can form crystals, causing the disease known as gout.