Liver enzyme clusters

Figure 1. The sequential emergence of enzyme clusters in developing liver.

The dimensions of cavities in enzymes differ considerably, depending on their physiological function. In many cases the clefts are occupied by clusters of organized water molecules. Such clusters can be seen in certain X-ray structures of enzymes (e.g., the structure of carboxypeptidase A determined by Lipscomb). If the clefts are deep, as in horse liver alcohol dehydrogenase, a channel for removal of water is present (Branden). 

Long recognized as an essential element for the growth of plants, molybdenum has never been directly demonstrated as a necessary animal nutrient. Nevertheless, it is found in several enzymes of the human body, as well as in 30 or more additional enzymes of bacteria and plants.632 Aldehyde oxidases,633 xanthine oxidase of liver and the related xanthine dehydrogenase, catalyze the reactions of Eqs. 16-58 and 16-59 and contain molybdenum that is essential for catalytic activity. Xanthine oxidase also contains two Fe2S2 clusters and bound FAD. The enzymes can also... 

The presence of zinc at the catalytic site of liver alcohol dehydrogenase suggests comparison with other zinc-dependent enzymes [164], and three are shown in Fig. 37. The hand and geometry of the zinc environment is invariant with respect to the proton abstractor (L4 and Fig. 37), the zinc atom, substrate site, water position, and protein ligand cluster. Ligand LI is in each case histidine, and the planes of the... 

Peroxisomes are small granules arranged in clusters around the smooth ER and glycogen stores. They contain about 50 enzymes, some of which are used in respiration, purine catabolism and alcohol metabolism. They are responsible for about 20% of the oxygen consumption in the liver via a respiratory pathway that produces heat rather than ATP as its product. They differ from lysosomes in that they are not formed from outgrowths of the Golgi apparatus but are self-replicating, rather like mitochondria. They also play an important role in the metabolism of fatty acids as well as cholesterol and bile acid synthesis. 

MPP+ is a potent inhibitor of oxidation of the NAD+-linked substrates pyruvate/malate and glu-tamate/malate in isolated rat liver and brain mitochondria, while leaving the oxidation of succinate unaffected (Nicklas et al., 1985). The locus of inhibition of the mitochondrial respiration is assumed to be between the highest potential Fe-S cluster in NADH dehydrogenase and the coenzyme Q located probably at the rotenone-binding site (Ramsay et al., 1991). As a consequence of inhibition of respiration, cellular energy supplies in the form of ATP would rapidly be consumed, followed by depolarization of membranes, probable Ca influx and overstimulation of Ca +-dependent lysosomal enzymes. 

P450 4F11 is another member of the CYP4A gene cluster found on chromosome 19 . Expression has been demonstrated primarily in liver, with some expression also in kidney, heart, and skeletal muscle. No other information is presently available, although it might be expected to be capable of leukotriene hydroxylation based upon its similarity to other P450 4F enzymes. 

Hie expression of recombinant mammalian liver ferrochelatases in Escherichia coli [4, 5], allowed the production of increased amounts of the enzyme and led to the unexpected discovery of a [2Fe-2S] cluster in the mammalian enzymes (mouse [6] and human [7]). The large amoimts of protein made available using heterologous over-producing systems allowed detailed spectroscopic studies on the cluster-containing ferrochelatases. Yeast Saccharomyces cerevisiae) ferrochelatase, which is devoid of an iron-sulfur cluster, has also been extensively studied and several site-directed mutants have been produced [8], making it a powerful model system to study the mechanism of this enzyme. 

Groups of secretory cells in glands such as the salivary glands, the pancreas, and the liver. Acini means shaped like a cluster of grapes, which is indicative of the shape of these organized clusters of cells. Their secretions of enzymes and bile feed into ducts that empty into the digestive tract. 

---