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Multiple Choice Questions- Haem synthesis and Degradation

The rise in concentration during lead exposure is a function first of decreased activity of ALA dehydratase (ALAD), which is uniquely sensitive to lead toxicity, and subsequently of increased activity of the initial and rate-limiting enzyme of haem biosynthesis, ALA synthase (Meredith et al., 1978).

AB - Haem is a prosthetic group for haem proteins, which play an essential role in oxygen transport, respiration, signal transduction, and detoxification. In haem biosynthesis, the haem precursor protoporphyrin IX (PP IX) must be accumulated into the mitochondrial matrix across the inner membrane, but its mechanism is largely unclear. Here we show that adenine nucleotide translocator (ANT), the inner membrane transporter, contributes to haem biosynthesis by facilitating mitochondrial accumulation of its precursors. We identified that haem and PP IX specifically bind to ANT. Mitochondrial uptake of PP IX was inhibited by ADP, a known substrate of ANT. Conversely, ADP uptake into mitochondria was competitively inhibited by haem and its precursors, suggesting that haem-related porphyrins are accumulated into mitochondria via ANT. Furthermore, disruption of the ANT genes in yeast resulted in a reduction of haem biosynthesis by blocking the translocation of haem precursors into the matrix. Our results represent a new model that ANT plays a crucial role in haem biosynthesis by facilitating accumulation of its precursors into the mitochondrial matrix.

Mechanism and sterochemistry of vinyl group formation in haem biosynthesis

Insulin Biosynthesis, Secretion, and Action | …

N2 - Haem is a prosthetic group for haem proteins, which play an essential role in oxygen transport, respiration, signal transduction, and detoxification. In haem biosynthesis, the haem precursor protoporphyrin IX (PP IX) must be accumulated into the mitochondrial matrix across the inner membrane, but its mechanism is largely unclear. Here we show that adenine nucleotide translocator (ANT), the inner membrane transporter, contributes to haem biosynthesis by facilitating mitochondrial accumulation of its precursors. We identified that haem and PP IX specifically bind to ANT. Mitochondrial uptake of PP IX was inhibited by ADP, a known substrate of ANT. Conversely, ADP uptake into mitochondria was competitively inhibited by haem and its precursors, suggesting that haem-related porphyrins are accumulated into mitochondria via ANT. Furthermore, disruption of the ANT genes in yeast resulted in a reduction of haem biosynthesis by blocking the translocation of haem precursors into the matrix. Our results represent a new model that ANT plays a crucial role in haem biosynthesis by facilitating accumulation of its precursors into the mitochondrial matrix.

The steps within the haem biosynthetic pathway which have been used to measure effect are: 1) inhibition of delta-aminolaevulinic acid dehydratase (ALAD); 2) urinary excretion of delta-aminolaevulinic acid (ALAU); (3) the accumulation of zinc protoporphyrin (ZPP) in erythrocytes arising from the inhibition of the enzyme ferrochelatase or the iron transport system.

Insulin Biosynthesis, Secretion, and Action

Haem is a prosthetic group for haem proteins, which play an essential role in oxygen transport, respiration, signal transduction, and detoxification. In haem biosynthesis, the haem precursor protoporphyrin IX (PP IX) must be accumulated into the mitochondrial matrix across the inner membrane, but its mechanism is largely unclear. Here we show that adenine nucleotide translocator (ANT), the inner membrane transporter, contributes to haem biosynthesis by facilitating mitochondrial accumulation of its precursors. We identified that haem and PP IX specifically bind to ANT. Mitochondrial uptake of PP IX was inhibited by ADP, a known substrate of ANT. Conversely, ADP uptake into mitochondria was competitively inhibited by haem and its precursors, suggesting that haem-related porphyrins are accumulated into mitochondria via ANT. Furthermore, disruption of the ANT genes in yeast resulted in a reduction of haem biosynthesis by blocking the translocation of haem precursors into the matrix. Our results represent a new model that ANT plays a crucial role in haem biosynthesis by facilitating accumulation of its precursors into the mitochondrial matrix.

This has provoked a reassessment of the effect of lead on haem biosynthesis, a pathway which is particularly sensitive to an increased concentration of lead in the body.

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Insulin is produced in the beta cells of the pancreatic islets


Pyroluria - Health - Science - Spirit

(2014) The Alternative Haem Biosynthesis Pathway: Structure, Function and Properties of Sirohaem Decarboxylase. Doctor of Philosophy (PhD) thesis, University of Kent,. (Full text available)

Letrozole 2.5 mg Film-coated tablets - - (eMC)

Roels HA, Buchet J-P, Lauwerys R, Hubermont G, Bruaux P, Claeys- Thoreau F, Lafontaine A, & van Overschelde J (1976) Impact of air pollution by lead on the haem biosynthetic pathway in school-age children.

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