Haem degradation

Zinc protoporphyrin IX is a normal metabolite that is formed in trace amounts during haem biosynthesis. However, in iron deficiency or in impaired iron utilization, zinc becomes an alternative substrate for ferrochelatase and elevated levels of zinc protoporphyrin IX, which has a known low affinity for oxygen, are formed. This zinc-for-iron substitution is one of the first biochemical responses to iron depletion, and erythrocyte zinc protoporphyrin is therefore a very sensitive index of bone-marrow iron status (Labbe et ah, 1999). In addition, zinc protoporphyrin may regulate haem catabolism by acting as a competitive inhibitor of haem oxygenase, the key enzyme of the haem degradation pathway. However, it has been reported... 

Carbon monoxide is released in the first step of the haem degradation pathway. Haem o ygenase cleaves a carbon-carbon bond and introduces two carbonyl groups to form amides, giving ferribiliverdin. This molecule of CO can then go on to up-regulate many en mes including the ones in this cycle. 

S.B. (1981). Mechanism of quercetin oxy-mode for haem degradation. Tetrahedron... 

In the enterocyte as it enters the absorptive zone near to the villus tips, dietary iron is absorbed either directly as Fe(II) after reduction in the gastrointestinal tract by reductants like ascorbate, or after reduction of Fe(III) by the apical membrane ferrireductase Dcytb, via the divalent transporter Nramp2 (DCT1). Alternatively, haem is taken up at the apical surface, perhaps via a receptor, and is degraded by haem oxygenase to release Fe(II) into the same intracellular pool. The setting of IRPs (which are assumed to act as iron biosensors) determines the amount of iron that is retained within the enterocyte as ferritin, and that which is transferred to the circulation. This latter process is presumed to involve IREG 1 (ferroportin) and the GPI-linked hephaestin at the basolateral membrane with incorporation of iron into apotransferrin. (b) A representation of iron absorption in HFE-related haemochromatosis. 

The first of the haem uptake systems to be characterized at molecular level was that of Yersinia enterolitica, which closely resembles a typical siderophore uptake system (Stojiljkovic and Hantke, 1992, 1994), including a TonB-dependent outer membrane receptor for haem, a periplasmic binding protein, and a cytoplasmic membrane transport system. There also seems to be a protein that degrades haem and liberates haem iron within the cell. TonB-dependent outer membrane receptor proteins for haem have been cloned and sequenced from Shigella dysenteriae and E. coli (Mills and Payne, 1995 Torres and Payne, 1997), while in Vibrio cholera two genes are required for haem utilization, one an outer membrane receptor a second which may have a TonB-like function (Henderson and Payne, 1994). 

Fig. 5.7. In green sulfur bacteria and in some archaebacteria, a reverse citric acid cycle is used for the assimilation of C02. It must be assumed that this was the original function of the citric acid cycle that only secondarily took over the role as a dissimulatory and oxidative process for the degradation of organic matter. A major enzyme here is 2-oxoglutarate ferredoxin for C02 fixation. Note that it, like several other enzymes in the cycle, uses Fe/S proteins. One is the initial so-called complex I which has eight different Fe/S centres of different kinds but no haem (see also other early electron-transfer chains, e.g. in hydrogenases).

Sterols Adrenal cortex, testes, ovaries Synthesis and degradation Haem Fe, P-450 enzymes... 

In addition to the common pathways, glycolysis and the TCA cycle, the liver is involved with the pentose phosphate pathway regulation of blood glucose concentration via glycogen turnover and gluconeogenesis interconversion of monosaccharides lipid syntheses lipoprotein formation ketogenesis bile acid and bile salt formation phase I and phase II reactions for detoxification of waste compounds haem synthesis and degradation synthesis of non-essential amino acids and urea synthesis. 

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