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Hepatic heme metabolism and its control
The Yale Journal of Biology and Medicine
|January 1, 1979
Summary
This review explores hepatic heme biosynthesis control, highlighting δ-aminolevulinic acid synthetase regulation by heme and dietary factors like glucose. It also examines heavy metal impacts on heme metabolism.
Area of Science:
- Biochemistry
- Heme Metabolism
- Hepatic Biosynthesis
Background:
- Heme is crucial for cellular functions, and its biosynthesis is tightly regulated.
- Hepatic heme biosynthesis is controlled primarily by the enzyme δ-aminolevulinic acid synthetase (ALAS).
- ALAS activity is influenced by heme levels, dietary intake, and heavy metals.
Purpose of the Study:
- To review the control mechanisms of hepatic heme biosynthesis.
- To elucidate the regulatory roles of heme, glucose, and heavy metals in heme metabolism.
- To discuss the physiological significance of these regulatory pathways.
Main Methods:
- Review of existing basic and clinical studies on heme metabolism.
- Analysis of experimental data concerning enzyme kinetics and metabolic pathways.
- Comparison of regulatory mechanisms across different organisms and conditions.
Main Results:
- Heme and dietary carbohydrates (glucose effect) repress δ-aminolevulinic acid synthetase activity.
- The glucose effect in mammals is not mediated by cyclic AMP, unlike in E. coli.
- Iron and cobalt inhibit heme synthesis and decrease cytochrome P-450, while increasing heme oxygenase activity.
Conclusions:
- Hepatic heme biosynthesis is primarily regulated by a feedback loop involving heme and the enzyme δ-aminolevulinic acid synthetase.
- Dietary factors, particularly carbohydrates, play a significant role in modulating heme synthesis.
- While heavy metals affect heme metabolism, heme itself is considered the primary physiological regulator.