Enzymic defence mechanisms

The free-radical defence mechanisms utilized by the brain are similar to those found in other tissues. The enzymes SOD, catalase, glutathione peroxidase, and the typical radical scavengers, ascorbate, vitamin E and vitamin A are present in the brain, as they are in peripheral tissues. However, the brain may actually be slightly deficient in some of these defence mechanisms when compared to the amounts present in other tissues. 

Catalase is one of the oldest known enzymes and was developed when life became aerobic, i.e. when organisms started to use oxygen. When a cell uses oxygen in its metabolism HP is very often produced as a by-product. However HP is toxic to the cells, so they need some defence mechanism. Catalase was invented by the evolution to protect living cells from HP. 

Cytokines are peptides that are produced and secreted by cells of the immune system. They organise the immune response to invasion by a pathogen by communicating between the different cells. They are synthesised in the immune cells as precursor proteins (pro-proteins) from which a peptide is removed by a proteolytic enzyme to produce the active cytokine, prior to secretion. This enzyme is a serine protease. Perhaps surprisingly, some viruses are capable of synthesising serpins which inhibit this enzyme in the immune cells, so that secretion does not occur and communication and integration of the immune response to the viral infection is lost. This is one of many biochemical mechanisms by which pathogens can reduce or overcome the defence mechanisms of the host (Chapter 17). 

Superoxide dismutases (SOD EC 1.15.1.1) constitute a group of metalloisoenzymes that neutralise the very reactive superoxide radical, generated in the cell as a by-product of the reduction of molecular oxygen (Salin, 1988). SOD is a highly efficient enzyme system involved in the cellular antioxidant system (cf. section on defence mechanisms). 

As an indirect effect of increased metal uptake, the physiological state of the cell can alter and defence mechanisms can be induced. Phytochelatin (metal binding proteins) synthesis and induction of free radical quenching enzymes and metabolites were frequently observed. Especially the latter can protect membranes against oxidative breakdown. 

This chapter focuses on recent data in areas where the enzymes of whole pathways and the genes for key enz)nnes for alkaloids have been isolated. We are aware that the field of alkaloids is much larger and comprises more strucfural groups. More information is found in Chapter 7 (this volume) and Chapter 2 in Volume 39 of this series (Wink, 2010). These studies have improved our understanding of the formation, mobilization and sequestration of alkaloids, and fheir role in plant defence mechanisms (Hashimoto and Ya-mada, 1994 Facchini, 2001 Zenk and Juenger, 2007 Liscombe and Facchini, 2008 Ziegler and Facchini, 2008). 

The benzylisoquinolines are formed from two molecules of fhe aromafic amino acid, tyrosine. In the past ten years, this pathway has been probed at the enzyme and gene level. The recent linking of the phloem-specific expression of tyrosine/Dopa decarboxylase (TYDC) genes with the bios)mthesis of the isoquinoline alkaloids in the opium poppy, Papaver somniferum (Facchini and De Luca, 1994, 1995, 2008 Liscombe and Facchini, 2008), and the association with alkaloid accumulation as part of the plant defence mechanism (Wink, 1993 Facchini et al, 1996) are of particular interest in furthering our knowledge of the location of alkaloid biosynthesis. 

There is considerable body of (indirect) evidence which makes oxidative stress one of the best accepted hypothesis for explaining the cause of Parkinson s disease. For example, the Fe(II)/Fe(III) ratio in the substantia nigra is shifted from 2 1 in the normal brain to 1 2 in Parkinsonian brain.131,132 In the Parkinsonian brain several enzymes which constitute the antioxidative defence mechanisms (glutathione peroxidase, catalase) have a decreased activity, while the activity of superoxide dismutase is increased, relative to the normal brain.133 Furthermore, specific products of radical damage, such as lipid hydroperoxides, were detected at a 10-fold increased level in the Parkinsonian brain.134... 

Early biological effects Initial reactions towards the presence of contaminants Defence mechanisms are a special case of early biological effects. They are either adaptive or defensive reactions and do not represent actual toxic damage. Extrusion of chemicals outside cells by protein pumps Induction of metal-binding proteins or biotransformation enzymes for elimination... 

Oxynitrilases or hydroxynitrile lyases (HNL) constitute a group of enzymes that catalyze the reversible addition of HCN to ketones and aldehydes. The natural role of these enzymes is a defence mechanism of higher plants against herbivores, whereby HCN is liberated from cyanoglucosides such as prunasin (almond, cherry, apple) by the action of a glycosidase and a hydroxynitrile lyase. 

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