Centres kidney

As stated at the beginning of this article, the liver is the most intensively studied animal tissue in biochemistry. In the context of the role of free radicals in human diseases, the liver is not obviously at centre stage, since heart disease and cancer are more important in the industrialized world than, for example, cirrhosis. Free-radical biochemistry of the liver will remain a fertile area of work, however, not least because so many original ideas and techniques are developed there and then applied to the study of other tissues. The increasing use of liver transplantation, following the acceptance of kidney and heart transplants as almost routine, will surely increase the interest in the study of ischaemia-reperfusion injury in... 

Fig. 6.8 Electron photomicrograph of mouse kidney mitochondria. The structure of both the cytoplasmatic membrane (centre) and the mitochondrial membranes is visible on the ultrathin section. Magnification 70,000x. (By courtesy of J. Ludvik)... 

Finally we should briefly mention the purple acid phosphatases, which, unlike the alkaline phosphatases, are able to hydrolyse phosphate esters at acid pH values. Their purple colour is associated with a Tyr to Fe(III) charge transfer band. The mammalian purple acid phosphatase is a dinuclear Fe(II)-Fe(III) enzyme, whereas the dinuclear site in kidney bean purple acid phosphatase (Figure 12.13) has a Zn(II), Fe(III) centre with bridging hydroxide and Asp ligands. It is postulated that the iron centre has a terminal hydroxide ligand, whereas the zinc has an aqua ligand. We do not discuss the mechanism here, but it must be different from the alkaline phosphatase because the reaction proceeds with inversion of configuration at phosphorus. 

The anorexia suffered by cancer patients is likely to arise from a combination of psychological stress, altered senses of taste and smell and increased levels of cytokines, which influence the appetite and satiety centres in the hypothalamus. There are several consequences micronutrient intake will be diminished and this may contribute to the signs and symptoms of the disease. Plasma amino acid levels will fall, as in starvation (Chapter 16). Synthesis of glutamine (by muscle, adipose and lung), aspartate (by liver), glutathione (by the intestine) and arginine (by the kidney) will all be compromised. The metabolic significance of all of these is discussed in Chapter 18. 

Heat stroke is the state in which heat stress induces a dangerously high core temperature that leads to tissue damage and particularly cerebral disturbance. The core temperature usually exceeds 40°C. The condition may follow heat exhaustion but the temperature rise may occur before salt or water depletion have had time to become manifest. Many organ systems may be affected by acute heat stroke including the brain, kidney, liver and muscles. Disturbance of the hypothalamic heat regulatory centre can lead to a loss of physiological responses to the... 

Isoniazid is completely absorbed on oral administration and penetrates all tissues of the body. Peak plasma levels are reached within one hour and persists for 24 hours. It penetrates intraceUularly and diffuses into macrophages and the necrotic centres. It is metabolized in liver by acetylation and isoniazid metabolites and a small amount of unchanged drug is excreted mainly by kidney. 

Kidney Disease. - Zhong and colleagues have detected carbon-centred radical adducts of POBN in urine from rats subjected to IR of the kidney. Animals given glycine sustained lower levels of kidney damage than the control-treated animals. Glycine also caused a dramatic reduction in the concentration of radical adducts detected in the urine.346... 

Benzoquinone depresses respiration in tissue preparations. Large doses induce local irritation, clonic convulsions, decreased blood pressure and death due to paralysis of the medullary centres. Signs of kidney damage were observed in severely poisoned animals (lARC, 1977). 

Figure 54 Renal images obtained using 99raTc-DTPA showing a normal right kidney and impaired function of the left kidney. The 4 "Tc activity can be seen to accumulate in the bladder at the bottom centre with increasing elapsed time from (a) to (c). (Courtesy of the Nuclear Medicine Department, Queen Elizabeth Hospital, Birmingham, UK)...

The purple acid phosphatases (PAPs) are a class of phosphoprotein phosphatases which possess a p-oxo(hydroxo)-bridged dinuclear iron centre. An enzyme has been isolated from beef spleen which is purple in colour, while a violet phosphatase has been characterised from red kidney beans (KBPase). This latter enzyme consists of two subunits with M = 58200 and contains two equivalents of Zn(II) and Fe(III) per dimer which are essential for catalytic activity. KBPase hydrolyses nucleosidetriphos-phates as well as activated phosphomonoesters such as 4-nitrophenylphosphate or a-naphthyl phosphate (Beck et al., 1986). As with the beef spleen enzyme, KBPase is inhibited by tetrahedral oxoanions such PO and AsO . 

Autosomal recessive cystinosis is caused by an enzyme-induced blockage of cystine degradation, particularly in the RES lysosomes of the bone marrow, liver, spleen and kidneys. Especially in the stellate cells of the spleen and to a lesser extent of the hepatic lobule centres, hexagonal and rectangular cystine crystals are found, pointing at an early stage to cystinosis. There is evidence of hepatosplenomegaly and microvesicular steatosis. The clinical picture of the infantile type presents as a Fan-coni syndrome, (s. pp 593, 597) The children affected die in the first five years of life. 

Kadkhodaee M, Hanson GR,Towner RA, Endre ZH Detection of hydroxyl and carbon-centred radicals by EPR spectroscopy after Ischaemia and reperfuslon of the rat kidney. Free RadIc.Res. 25 31-42,1996... 

Drug metabolism may be influenced by stereochemical factors if the molecule in question possesses one or more chiral centres. Examples of drugs that show stereochemical differences in rates of metabolism include a-methyldopa (where the (S) isomer is decarboxylated more rapidly than the (R) isomer) and the enantiomers of warfarin, which are reduced at different rates. The well-known endogenous compound mevalonic acid (3,5-dihydroxy-3-methylpentanoic acid) is chiral and exists as two enantiomers. When a racemic mixture of mevalonic acid is fed to animals, one optical isomer is absorbed and metabolised, while virtually all of the other isomer is excreted by the kidneys into the urine. 

We thank our colleagues and members of the Madrenas and McCormick laboratories for helpful discussions and ideas. This work was supported by the Canadian Institutes of Health Research (CIHR), the Kidney Foundation of Canada, and the London Health Sciences Centre Multi-Organ Transplant Program. C.B. was supported by a fellowship from the Ontario Research and Development Fund, J.K.M. is a recipient of a CIHR New Investigator Award, and J.M. holds a Canada Research Chair in Transplantation and Immunobiology. 

Groote Schuur Hospital, University of Cape Town, South Africa Witwatersrand University, Johannesburg, South Africa ygerberg Hospital, University of Stellenbosch, South Africa Klhris Hani Baragwanath Hospital, Soweto, South Africa Dr Salma Suleiman Dialysis Kidney Transplant Centre, Khartoum, Sudan... 

In a prospective study performed in Khartoum Kidney Dialysis Centre and Sheffield Kidney Institute 19 renal biopsies out of a series 23 patients with severe (39%), moderate (35%) and mild intoxication (26%) were studied under light microscopy. Glomerular injury observed in 94% of the biopsies in the form of hy-percellularity, membranous proUferation, glomerular swelling, capsular drop and accentuated lobular architecture [38]. 

Dr. Salma Suleiman Dialysis and Kidney Transplantation Centre PO Box 10716 Khartoum Sudan... 

The presence of Hg, Cd, Cu and Zn induces the production of thioneins in the liver and kidneys of mammals. Between 4 and 12 metal centres can be bound by one thionein Zn Hg, Cd centres are likely to be in tetrahedral environments, while Cu may be 3-coordinate. The structure of the Cd/Zn-containing metallothionein isoform II from rat liver has been determined by X-ray difiraction, and Figure 28.6a illustrates the folded protein chain consisting of 61 amino acid residues of which 20 are Cys groups. One Cd + and two Zn centres are bound in... 

---