Tymoczko Berg Stryer Biochemistry: A Short Course Second Edition CHAPTER 31 Amino Acid Synthesis 2013 W. H. Freeman and Company
Chapter 31 Outline
Although the atmosphere is approximately 80% nitrogen, this vital element is not available to the majority of organisms. However, a few organisms, such as the diazotrophic (nitrogen fixing) bacteria, can convert nitrogen gas (N 2 ) into the biochemically more useful NH 3. The Haber process, devised in 1910, allows for industrial fixation of nitrogen. Lightening strikes are also capable of fixing nitrogen.
The nitrogenase complex of diazotrophic organisms is responsible for the fixation of N 2 into NH 3. The complex consists of two components: 1. The reductase provides high energy electrons, in the form of ferredoxin, for reducing power. 2. The nitrogenase uses the electrons to reduce N 2 to NH 3 according to the following reaction. In aqueous solution, NH 3 acquires a proton to form NH 4+. ATP is required not to power the reaction, but to make the exergonic reaction kinetically feasible.
The reductase and the nitrogenase are iron sulfur proteins. The reductase, also called the iron protein, transfers electrons from ferredoxin to the nitrogenase. A site on the nitrogenase called the P cluster accepts the electrons. From the P cluster, the electrons flow to the MoFe center, the site where N 2 is reduced to ammonia. The MoFe center contains both molybdenum and iron, which are required for the reduction.
Glutamate dehydrogenase catalyzes the incorporation of ammonia into α ketoglutarate to generate glutamate. Glutamate serves as a nitrogen source for biosynthesis reactions, such as the synthesis of amino acids from α ketoacids.
Glutamine synthetase incorporates another nitrogen into glutamate in an amidation reaction to form glutamine. Glutamine is a versatile nitrogen donor.
The carbon skeletons for amino acid synthesis are provided by intermediates of the glycolytic pathway, the citric acid cycle, and the pentose phosphate pathway.
Amino acids that can be synthesized by humans are called nonessential amino acids, and are usually synthesized by simple reactions. Amino acids that are required in the diet are called essential amino acids. These amino acids usually have complex synthetic pathways and cannot be synthesized by humans. A deficiency in even one essential amino acid can have severe physiological consequences.
Transamination reactions are catalyzed by transaminases (aminotransferases). These enzymes require the coenzyme pyridoxal phosphate, which is derived from pyridoxine (vitamin B 6 ).
The glycolytic intermediate 3 phosphoglycerate is the precursor for serine. Serine, in turn, is metabolized to cysteine and glycine. The synthesis of glycine requires the cofactor tetrahydrofolate.
Tetrahydrofolate is composed of a pteridine ring, p aminobenzoate, and one or more glutamates. Tetrahydrofolate is derived from folic acid (vitamin B 9 ). Tetrahydrofolate, which carries single carbon atoms in a variety of oxidation states, is especially important for the embryonic development of the nervous system.
S Adenosylmethionine is synthesized from methionine and ATP in an unusual reaction in which the triphosphate of ATP is cleaved to pyrophosphate and phosphate.
After donation of a methyl group by S adenosylmethionine, the resulting S adenosylhomocysteine is cleaved to yield adenosine and homocysteine. Methionine is regenerated from homocysteine by the methylcobalamin dependent enzyme methionine synthase, which catalyzes the transfer of a carbon from N 5 methyltetrahydrofolate. The use of S adenosylmethionine and its regeneration constitute the activated methyl cycle.
S Adenosylmethionine is also a precursor for the plant hormone ethylene that induces ripening of fruit.
Individuals with high blood levels of homocysteine are at greater risk for cardiovascular disease. The most common cause of increased blood homocysteine is a lack of cystathionine synthase activity, the enzyme that converts homocysteine into cysteine.
Feedback inhibition is a common means of regulating metabolic flux. In feedback inhibition, the final product in a pathway inhibits the enzyme catalyzing the committed step. The committed step in serine synthesis is catalyzed by 3 phosphoglycerate dehydrogenase, which is inhibited by serine.
Branched pathways are regulated by one of several different methods. 1. Feedback inhibition and activation: If two pathways have an initial common step, one pathway is inhibited by its own product and stimulated by the product of the other pathway. Threonine deaminase illustrates this type of regulation. 2. Enzyme multiplicity: The committed step is catalyzed by two or more enzymes with differing regulatory properties. Three distinct aspartate kinases control the synthesis of threonine, methionine, and lysine in E. coli. 3. Cumulative feedback inhibition: A common step for several pathways is partly inhibited independently by each of the various end products. This type of regulation is illustrated by glutamine synthetase, which is inhibited by a host of biochemicals.