Heme, or haem, is a precursor to hemoglobin, which is necessary to bind oxygen in the bloodstream. Heme is biosynthesized in both the bone marrow and the liver.
Aminolevulinic acid synthase (ALA synthase, ALAS, or delta-aminolevulinic acid synthase) is an enzyme (EC 2.3.1.37) that catalyzes the synthesis of δ-aminolevulinic acid (ALA) the first common precursor in the biosynthesis of all tetrapyrroles such as hemes, cobalamins and chlorophylls. The reaction is as follows:
Gunther disease is a congenital form of erythropoietic porphyria. The word porphyria originated from the Greek word porphura. Porphura actually means "purple pigment", which, in suggestion, the color that the body fluid changes when a person has Gunther's disease. It is a rare, autosomal recessive metabolic disorder affecting heme, caused by deficiency of the enzyme uroporphyrinogen cosynthetase. It is extremely rare, with a prevalence estimated at 1 in 1,000,000 or less. There have been times that prior to birth of a fetus, Gunther's disease has been shown to lead to anemia. In milder cases patients have not presented any symptoms until they have reached adulthood. In Gunther's disease, porphyrins are accumulated in the teeth and bones and an increased amount are seen in the plasma, bone marrow, feces, red blood cells, and urine.
Sideroblastic anemia, or sideroachrestic anemia, is a form of anemia in which the bone marrow produces ringed sideroblasts rather than healthy red blood cells (erythrocytes). In sideroblastic anemia, the body has iron available but cannot incorporate it into hemoglobin, which red blood cells need in order to transport oxygen efficiently. The disorder may be caused either by a genetic disorder or indirectly as part of myelodysplastic syndrome, which can develop into hematological malignancies.
Diamond–Blackfan anemia (DBA) is a congenital erythroid aplasia that usually presents in infancy. DBA causes low red blood cell counts (anemia), without substantially affecting the other blood components, which are usually normal. This is in contrast to Shwachman–Bodian–Diamond syndrome, in which the bone marrow defect results primarily in neutropenia, and Fanconi anemia, where all cell lines are affected resulting in pancytopenia. There is a risk to develop acute myelogenous leukemia (AML) and certain other cancers.
Protoporphyrinogen oxidase or protox is an enzyme that in humans is encoded by the PPOX gene.
GATA-binding factor 1 or GATA-1 is the founding member of the GATA family of transcription factors. This protein is widely expressed throughout vertebrate species. In humans and mice, it is encoded by the GATA1 and Gata1 genes, respectively. These genes are located on the X chromosome in both species.
Erythropoietic porphyria is a type of porphyria associated with erythropoietic cells. In erythropoietic porphyrias, the enzyme deficiency occurs in the red blood cells.
Protein 4.1,, is a protein associated with the cytoskeleton that in humans is encoded by the EPB41 gene. Protein 4.1 is a major structural element of the erythrocyte membrane skeleton. It plays a key role in regulating membrane physical properties of mechanical stability and deformability by stabilizing spectrin-actin interaction. Protein 4.1 interacts with spectrin and short actin filaments to form the erythrocyte membrane skeleton. Mutations of spectrin and protein 4.1 are associated with elliptocytosis or spherocytosis and anemia of varying severity.
Krueppel-like factor 1 is a protein that in humans is encoded by the KLF1 gene. The gene for KLF1 is on the human chromosome 19 and on mouse chromosome 8. Krueppel-like factor 1 is a transcription factor that is necessary for the proper maturation of erythroid cells.
Aminolevulinic acid dehydratase (porphobilinogen synthase, or ALA dehydratase, or aminolevulinate dehydratase) is an enzyme (EC 4.2.1.24) that in humans is encoded by the ALAD gene. Porphobilinogen synthase (or ALA dehydratase, or aminolevulinate dehydratase) synthesizes porphobilinogen through the asymmetric condensation of two molecules of aminolevulinic acid. All natural tetrapyrroles, including hemes, chlorophylls and vitamin B12, share porphobilinogen as a common precursor. Porphobilinogen synthase is the prototype morpheein.
Hexokinase-1 (HK1) is an enzyme that in humans is encoded by the HK1 gene on chromosome 10. Hexokinases phosphorylate glucose to produce glucose-6-phosphate (G6P), the first step in most glucose metabolism pathways. This gene encodes a ubiquitous form of hexokinase which localizes to the outer membrane of mitochondria. Mutations in this gene have been associated with hemolytic anemia due to hexokinase deficiency. Alternative splicing of this gene results in five transcript variants which encode different isoforms, some of which are tissue-specific. Each isoform has a distinct N-terminus; the remainder of the protein is identical among all the isoforms. A sixth transcript variant has been described, but due to the presence of several stop codons, it is not thought to encode a protein. [provided by RefSeq, Apr 2009]
Cytochrome c oxidase I (COX1) also known as mitochondrially encoded cytochrome c oxidase I (MT-CO1) is a protein that is encoded by the MT-CO1 gene in eukaryotes. The gene is also called COX1, CO1, or COI. Cytochrome c oxidase I is the main subunit of the cytochrome c oxidase complex. In humans, mutations in MT-CO1 have been associated with Leber's hereditary optic neuropathy (LHON), acquired idiopathic sideroblastic anemia, Complex IV deficiency, colorectal cancer, sensorineural deafness, and recurrent myoglobinuria.
ATP-binding cassette sub-family B member 7, mitochondrial is a protein that in humans is encoded by the ABCB7 gene.
Succinyl-CoA ligase [ADP-forming] subunit beta, mitochondrial (SUCLA2), also known as ADP-forming succinyl-CoA synthetase (SCS-A), is an enzyme that in humans is encoded by the SUCLA2 gene on chromosome 13.
Mitoferrin-1 (Mfrn1) is a 38 kDa protein that is encoded by the SLC25A37 gene in humans. It is a member of the Mitochondrial carrier (MC) Superfamily, however, its metal cargo makes it distinct from other members of this family. Mfrn1 plays a key role in mitochondrial iron homeostasis as an iron transporter, importing ferrous iron from the intermembrane space of the mitochondria to the mitochondrial matrix for the biosynthesis of heme groups and Fe-S clusters. This process is tightly regulated, given the redox potential of Mitoferrin's iron cargo. Mfrn1 is paralogous to Mitoferrin-2 (Mfrn2), a 39 kDa protein encoded by the SLC25A28 gene in humans. Mfrn1 is highly expressed in differentiating erythroid cells and in other tissues at low levels, while Mfrn2 is expressed ubiquitously in non-erythroid tissues.
tRNA pseudouridine synthase A is an enzyme that in humans is encoded by the PUS1 gene.
Delta-aminolevulinate synthase 1 also known as ALAS1 is a protein that in humans is encoded by the ALAS1 gene. ALAS1 is an aminolevulinic acid synthase.
Glutaredoxin 5, also known as GLRX5, is a protein which in humans is encoded by the GLRX5 gene located on chromosome 14. This gene encodes a mitochondrial protein, which is evolutionarily conserved. It is involved in the biogenesis of iron- sulfur clusters, which are required for normal iron homeostasis. Mutations in this gene are associated with autosomal recessive pyridoxine-refractory sideroblastic anemia.
Mitochondrial ferritin is a ferroxidase enzyme that in humans is encoded by the FTMT gene.
