as a general base during this mechanism,. In the detailed reaction mechanism, the hydronium atoms that are added in come from a variety of residues that offer hydrogen bonds to facilitate ALA synthesis. ALA synthase removes the carboxyl group from glycine and the CoA from the succinyl-CoA by means of its prosthetic group pyridoxal phosphate (a vitamin b6 derivative), forming δ-aminolevulinic acid (dALA), so called because the amino group is on the fourth carbon atom in the molecule. This reaction mechanism is particularly unique relative to other enzymes that use the PLP cofactor because Glycine is initially deprotonated by a highly conserved active site lysine, leading to condensation with succinyl-CoA and loss of CoA. Protonation of the carbonyl group of the intermediate by an active site histidine leads to loss of the carboxyl group. The last intermediate is finally reprotonated to produce ALA. Dissociation of ALA from the enzyme is the rate limiting step of the enzymatic reaction and was shown to be depended upon a slow conformational change of the enzyme. The function of pyridoxal phosphate is to facilitate the removal of hydrogen, by utilizing the electrophilic pyridinium ring as an electron sink. The location of this enzyme in biological systems is indicative of the feedback that it may receive. ALA Synthase has been found in bacteria, yeast, avian and mammalian liver and blood cells and bone marrow. The location of this enzyme in animal cells is within the mitochondria. Since the enzyme appears to be located near its source of succinyl-CoA and the end of the heme pathway indicates that the starting and end points of heme biosynthesis serves as feedback for ALA synthase. ALA synthase is also inhibited by hemin and glucose. Biological function ALAS1 and ALAS2 catalyze the first step in the process of heme synthesis. It is the first irreversible step and is also rate limiting. This means that the beginning of the formation of hemes is very intentional and subject to a variety of areas of feedback. For example, the two substrates, oxaloacetate and glycine, are highly produced by and utilized in other essential biological processes such as glycolysis and the TCA cycle. The image below illustrates the heme synthesis pathway and the role ALAS plays. Disease relevance Aminolevulinic Acid Synthase Deficiency results in a lack of ability to create heme since its job is to catalyze the first step in the process. These