The Enzymatic Synthesis of δ-Aminolevulinic Acid

Kikuchi, Gorö; Kumar, A.; Talmage, Phyllis; Shemin, David

doi:10.1016/s0021-9258(19)77371-2

Cited by 281 publications

(18 citation statements)

References 13 publications

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“…26,46 ALAS2 is the rate-limiting enzyme in the heme biosynthesis pathway and catalyzes the condensation of glycine and succinyl-coenzyme A to 5-aminolevulinic acid in mitochondria. [47][48][49] Alas2 null mutant mice display decreased erythroid differentiation, aberrant iron accumulation, and increased oxidative stress. 46 Furthermore, a conserved regulatory region within intron 8 of Alas2, bound by Gata1, is required for its tissue-specific expression during erythroid differentiation.…”

Section: Discussionmentioning

confidence: 99%

The orphan nuclear receptor TR4 regulates erythroid cell proliferation and maturation

Lee

Takahashi

Shi

et al. 2017

Blood

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The orphan nuclear receptors TR4 (NR2C2) and TR2 (NR2C1) are the DNA-binding subunits of the macromolecular complex, direct repeat erythroid-definitive, which has been shown to repress and transcription during adult definitive erythropoiesis. Previous studies implied that TR2 and TR4 act largely in a redundant manner during erythroid differentiation; however, during the course of routine genetic studies, we observed multiple variably penetrant phenotypes in the mutants, suggesting that indirect effects of the mutation might be masked by multiple modifying genes. To test this hypothesis, mutant mice were bred into a congenic C57BL/6 background and their phenotypes were reexamined. Surprisingly, we found that homozygous null mutant mice expired early during embryogenesis, around embryonic day 7.0, and well before erythropoiesis commences. We further found that erythroid cells failed to fully differentiate and exhibited diminished proliferative capacity. Analysis of mutant erythroid cells revealed that reduced TR4 abundance resulted in decreased expression of genes required for heme biosynthesis and erythroid differentiation ( and ), but led to significantly increased expression of the proliferation inhibitory factor, cyclin dependent kinase inhibitor ( These studies support a vital role for TR4 in promoting erythroid maturation and proliferation, and demonstrate that TR4 and TR2 execute distinct, individual functions during embryogenesis and erythroid differentiation.

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Section: Discussionmentioning

confidence: 99%

The orphan nuclear receptor TR4 regulates erythroid cell proliferation and maturation

Lee

Takahashi

Shi

et al. 2017

Blood

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“…Upstream of almost all Group 1 mtr clusters is glnS , which plays an established role in heme biosynthesis by providing glutamate for the synthesis of the tetrapyrrole precursor 5-aminolevulinic acid ( 90 ). The frd operon could potentially play a parallel role by providing a source of succinate, which, if converted to succinyl coenzyme A (succinyl-CoA), can also generate 5-aminolevulinic acid ( 91 , 92 ). Another possible function of FrdABCD in conjunction with Mtr would be to support EET in both the oxidative and reductive directions, an intriguing possibility that warrants further study.…”

Section: Resultsmentioning

confidence: 99%

Evidence for Horizontal and Vertical Transmission of Mtr-Mediated Extracellular Electron Transfer among the Bacteria

Baker

Conley

Gralnick

et al. 2022

mBio

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While many metabolisms make use of soluble, cell-permeable substrates like oxygen or hydrogen, there are other substrates, like iron or manganese, that cannot be brought into the cell. Some bacteria and archaea have evolved the means to directly “plug in” to such environmental electron reservoirs in a process known as extracellular electron transfer (EET), making them powerful agents of biogeochemical change and promising vehicles for bioremediation and alternative energy.

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“…The presence of an inhibitor of ALA synthetase in aerobically grown R. 8pheroide8 was reported by Kikuchi, Kumar, Talmage & Shemin (1958), but without experimental details. The same authors found increases in total activity during purification of ALA synthetase, and similar increases have been observed in this Laboratory (Matthew, 1962).…”

Section: Discussionmentioning

confidence: 94%

Control of δ-aminolaevulate synthetase activity in Rhodopseudomonas spheroides

Marriott

Neuberger

Tait

1969

Biochemical Journal

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1. delta-Aminolaevulate synthetase from Rhodopseudomonas spheroides grown semi-anaerobically undergoes a spontaneous activation during the first hour after the disruption of cells when homogenates are stored at 4 degrees . 2. After cultures of R. spheroides growing semi-anaerobically are oxygenated no activation of delta-aminolaevulate synthetase occurs in cell extracts. Cessation of activation in extracts is almost complete 10min. after oxygenation of cells has begun. 3. A heat-stable fraction of low molecular weight from semi-anaerobic cells reactivates delta-aminolaevulate synthetase in extracts of oxygenated cells and appears to contain a compound responsible for the spontaneous activation. 4. A heat-stable fraction of low molecular weight from oxygenated cells inhibits the spontaneous activation in extracts of semi-anaerobic cells. 5. The effect of oxygen on the rate of bacteriochlorophyll synthesis in R. spheroides may be mediated through alterations in the concentrations of a low-molecular-weight activator and inhibitor of delta-aminolaevulate synthetase.

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The Enzymatic Synthesis of δ-Aminolevulinic Acid

Cited by 281 publications

References 13 publications

The orphan nuclear receptor TR4 regulates erythroid cell proliferation and maturation

The orphan nuclear receptor TR4 regulates erythroid cell proliferation and maturation

Evidence for Horizontal and Vertical Transmission of Mtr-Mediated Extracellular Electron Transfer among the Bacteria

Control of δ-aminolaevulate synthetase activity in Rhodopseudomonas spheroides

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