Enzyme regulation compartmentalization

Understand enzyme regulation via cellular enzyme levels, compartmentation, metabolic pathway regulation, and covalent modifications. 

Enzyme regulation and interpretation of activity assays A major uncertainty in using esterases to estimate cell lysis is the very broad nature of the assay. It is quite clear that FDA can be hydrolyzed by a number of different enzymes, including some of the extracellular enzymes describe above (e.g., Schnurer and Rosswall, 1982) obviously this is not compatible with the assumption that they are solely intracellular. Within cells, esterases are typically regulated by compartmentalization rather than other mechanisms, and so regulatory features are not likely to complicate interpretations of activity assays. 

Metabolism is tightly regulated by a number of mechanisms feedback inhibition, compartmentalization, covalent modification of enzymes (e.g., phosphorylation), and hormone action, among others. 

The role of GSH in cellular protection (see below) means that if depleted of GSH, the cell is more vulnerable to toxic compounds. However, GSH is compartmentalized, and this compartmentalization exerts an influence on the relationship between GSH depletion or oxidation and injury. The loss of reduced GSH from the cell leaves other thiol groups, such as those in critical proteins, vulnerable to attack with subsequent oxidation, cross-linking, and formation of mixed disulfides or covalent adducts. The sulfydryl groups of proteins seem to be the most susceptible nucleophilic targets for attack, as shown by studies with paracetamol (see chap. 7), and are often crucial to the function of enzymes. Consequently, modification of thiol groups of enzyme proteins, such as by mercury and other heavy metals, often leads to inhibition of the enzyme function. Such enzymes may have critical endogenous roles such as the regulation of ion concentrations, active transport, or mitochondrial metabolism. There is... 

The rate of photosynthesis does not depend on the amount of a single component (e.g., the activity of a particular enzyme). There is a wide range of possible regulatory factors, proven to exist in vitro, but the importance of which in vivo has still to be determined. In particular, there is a multitude of factors affecting the activity of the enzymes involved, with pH, ions, coenzymes, and metabolite effectors modulating the activity of every enzyme studied thus far. Compartmentation is the other key factor. The role of metabolite transport in the cell, particularly between chloroplast and cytosol, but also to and from mitochondria, vacuole, and other organelles, is now considered to be fundamental to the regulation of photosynthesis. In this chapter, we look at the factors considered to be of major importance... 

Spilatro, S. R., and Preiss, J. 1987. Regulation of starch synthesis in the bundle sheath and mesophyll of Zea mays L. Intercellular compartmentalization of enzymes of starch metabolism and the properties of the ADPglucose Pyrophosphorylases. Plant Physiol. 83, 621-627. 

Activation of caspases is irreversible, because it involves peptide-bond cleav e. This is unlike most other protein modifications which play a role in cellular regulation. Therefore, proteolysis is involved only in unidirectional, irreversible processes, such as the cell cycle and cell death. But, the possibilities to regulate irreversible reactions are rather limited. In a cascade of proteolytic reactions, the first enzyme in the chain is the most likely point of control. This is the initiator caspase. The signals controlling initiator caspases vary, there are both external and internal signals (Fig. 13.5). Several mechanisms control the irreversible activation of caspases, including phosphorylation, separation, and compartmentalization of pro-caspases and positive and n ative regulators. 

The biosynthesis of SM exhibits a remarkable complexity. Enzymes are specific for each pathway and are highly regulated in terms of compartmentation, time and space. The same is true for fhe mechanisms of accumulation or the site and time of storage. In general, we find fhaf fissues and organs which are important for survival and multiplication, such as epidermal and bark tissues, flowers, fruits and seeds, have distinctive profiles of SM, and secondary compounds are stored in high amounts in them. As an example, the complex pattern of alkaloid synfhesis, transporf and sforage is illustrated in Fig. 1.7. 

Compartmentation of substrate and enzyme. Enzymes can also be compartmentalised, like the hydrolytic enzymes found in the lysosome, but the release of these suicide enzymes during apoptosis is rather more of an on/off switch than a true regulation. 

The regulation of biochemical pathways is complex. It is achieved primarily by adjusting the concentrations and activities of certain enzymes. Control is accomplished by (1) genetic control, (2) covalent modification, (3) allosteric regulation, and (4) compartmentation. 

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