Return to List of Bioc 460 Lectures
 |
Department of Biochemistry http://www.biochem.arizona.edu/classes/bioc460/spring/springindex.html
|
Bioc 460 Spring 1999
Lecture 39 - Chapter 28
- Overview
of amino acid biosynthesis
- Nitrogen fixation in the biosphere
- Assimilation of NH4 into Glu and Gln
- Heme biosynthesis
Overview
of amino acid biosynthesis
Atmospheric nitrogen is reduced to ammonia (N2 ---> NH3) primarily by microorganisms that live in the soil and are associated with plant roots. Humans need to obtain 9 of the 20 amino acids from their diet because we lack the necessary enzymes for de novo biosynthesis. There are basically 20 different pathways to specify the synthesis of the 20 amino acids.
Figure 28.2, Figure 28.3
Table 28.1
Figure 28.7
Amino acid biosynthetic pathways have been investigated in bacteria and yeast and shown to be regulated by feedback inhibition. Several intricate feedback mechanisms have been discovered in bacteria in amino acid biosynthetic pathways containing branch points.
Figure 28.19
Pages 727-728
1. Sequential feedback
inhibition
2. Enzyme multiplicity
3. Concerted feedback inhibition
4. Cumulative feedback inhibition.
Why would these amino acid biosynthetic pathways be so tightly regulated?
Nitrogen fixation
in the biosphere
The nitrogen in amino acids, nucleotides and other biomolecules ultimately comes from atmospheric nitrogen. The conversion of N2 ---> NH3 is carried out by bacteria and blue-green algae. The best studied nitrogen-fixing soil bacteria is Rhizobium which invades the roots of leguminous plants such as soy bean. The biological process requires a complex enzymatic reaction involving multiple redox centers. The two primary enzymatic activities are the reductase and the nitrogenase.
The net reaction for nitrogen fixation is:
N2 + 8 e- + 16 ATP + 16 H2O ---> 2 NH3 + H2 + 16 ADP + 16 Pi + 8 H
Nitrate NO3- and nitrite NO2- ions are abundant in soil and can be converted to NH3 by essentially all plants and bacteria. Through the combined effect of nitrogen fixation and nitrate/nitrite reduction, the steady-state level of nitrogen in biosphere is maintained. Animals are at the mercy of plants and microbes for nitrogen!
Assimilation
of NH4 into Glu and Gln
The a amino group of most amino acids comes from glutamate via a transamination reaction. Glutamine also plays a pivotal role in donating nitrogen to a variety of compounds. NH4 is assimilated into glutamate by the glutamate dehydrogenase reaction (a reversible reaction). The enzyme glutamine synthetase catalyzes incorporation of NH4 into glutamine.
Page 717
The enzyme glutamine synthetase is an example of regulation by cumulative feedback inhibition. Glutamine is the source of nitrogen for a number of biomolecules including; tryptophan, histidine, carbamoyl phosphate, CTP, etc. The enzymatic activity is inhibited by each of these products such that it is maximally inhibited when all of these molecules are bound at the same time to the allosteric regulatory sites of glutamine synthetase. The activity of the enzyme is also subject to control by covalent modification, in this case, adenylation.
Figure 28.20
Figure 28.21
Heme
biosynthesis
The porphyrin ring of hemes is derived from reactions utilizing glycine as the source of nitrogen and for some of the carbon atoms (other carbon atoms come from acetate). The first step in the biosynthesis of porphyrins in mammals is the condensation of glycine and succinyl CoA to form d-aminolevulinate. Two molecules of d-aminolevulinate condense to form porphobilinogen which is the precursor to heme ring synthesis.
Page 733
Figure 28.28
Figure 28.29
Genetic defects in porphyrin metabolism have been identified. The most notable disease of this type is congenital erythropoietic porphyria which causes urine to turn red, the skin to become light sensitive and teeth to glow in the dark (red fluorescent teeth). Moreover, red blood cells are short-lived due to very low levels of heme and patients are anemic. One way people treated anemia in the middle ages was to drink blood. What does this sound like to you? click here to find out what I think of.
The cause of this disease is lack of the enzyme uroporphyrinogen III cosynthase which leads to a build-up of the symmetric (but physiological inert) intermediate uroporphyrinogen I. This molecule absorbs light readily.
Page 735
|
Department of Biochemistry http://www.biochem.arizona.edu/classes/bioc460/spring/springindex.html
|