Metabolic control, developments

Fell, D.A. (1992). Metabolic control analysis A survey of its theoretical and experimental development. Biochem. J. 286,313-330. 

Intensified metabolic control, especially in case of diabetes, demands minimal-invasive or non-invasive methods of analytical measurement. For this goal, a method has been developed to measure the blood glucose content in vivo, in direct contact with the skin, by means of diffuse reflection near infrared (NIR) spectroscopy on the basis of multivariate calibration and neural networks (Muller et al. [1997] Fischbacher et al. [1997] Danzer et al. [1998]). Because no patients with any standard blood glucose value are available in principle, a method of indirect calibration has... 

An early systematic approach to metabolism, developed in the late 1970s by Kacser and Burns [313], and Heinrich and Rapoport [314], is Metabolic Control Analysis (MCA). Anticipating systems biology, MCA is a quantitative framework to understand the systemic steady-state properties of a biochemical reaction network in terms of the properties of its component reactions. As emphasized by Kacser and Burns in their original work [313],... 

Although the importance of a systemic perspective on metabolism has only recently attained widespread attention, a formal frameworks for systemic analysis has already been developed since the late 1960s. Biochemical Systems Theory (BST), put forward by Savageau and others [142, 144 147], seeks to provide a unified framework for the analysis of cellular reaction networks. Predating Metabolic Control Analysis, BST emphasizes three main aspects in the analysis of metabolism [319] (i) the importance of the interconnections, rather than the components, for cellular function (ii) the nonlinearity of biochemical rate equations (iii) the need for a unified mathematical treatment. Similar to MCA, the achievements associated with BST would warrant a more elaborate treatment, here we will focus on BST solely as a tool for the approximation and numerical simulation of complex biochemical reaction networks. 

Women with PKU who become pregnant must be especially careful about the phenylalanine level in their blood so as not to adversely affect neurologic development in the fetus. Infants whose phenylketonuric mothers have not maintained adequate metabolic control during pregnancy have a high risk for mental retardation (although less profound than in a child with untreated PKU), microcephaly, and low birth weight. 

Secondary growth hormone insensitivity syndrome is thought to develop when chronic insulin deficiency and poor metabolic control occur in people with type 1 diabetes. High growth hormone concentrations are found in conjunction with low concentrations of IGF1. 

Bottom-up systems biology does not rely that heavily on Omics. It predates top-down systems biology and it developed out of the endeavors associated with the construction of the first mathematical models of metabolism in the 1960s [10, 11], the development of enzyme kinetics [12-15], metabolic control analysis [16, 17], biochemical systems theory [18], nonequilibrium thermodynamics [6, 19, 20], and the pioneering work on emergent aspects of networks by researchers such as Jacob, Monod, and Koshland [21-23]. 

Many methods have been developed for model analysis for instance, bifurcation and stability analysis [88, 89], parameter sensitivity analysis [90], metabolic control analysis [16, 17, 91] and biochemical systems analysis [18]. One highly important method for model analysis and especially for large models, such as many silicon cell models, is model reduction. Model reduction has a long history in the analysis of biochemical reaction networks and in the analysis of nonlinear dynamics (slow and fast manifolds) [92-104]. In all cases, the aim of model reduction is to derive a simplified model from a larger ancestral model that satisfies a number of criteria. In the following sections we describe a relatively new form of model reduction for biochemical reaction networks, such as metabolic, signaling, or genetic networks. 

For amino acids like tryptophan and serine, because of the difficulty in avoiding metabolic control, another technique was developed, i.e. intermediate addition of the corresponding amino acids 50). Amino acids are also produced by intact cells, cell-free enzyme preparations or immobilized enzymes51,52). 

A 43-year-old man with type 1 diabetes developed local pruritus, redness, and swelling 4—5 times a week, 15-20 minutes after an injection, subsiding within 1-2 hours (132). Later he had a generalized urticarial reaction 5 minutes after an injection. Insuhn lispro did not help. When checked for allergens, he was positive for all types of insulin and negative for additives. With oral mizolastine the local reactions abated for a week, but then reappeared with every injection. Generalized urticaria recurred later. With continuous subcutaneous insulin infusion the local reactions immediately disappeared and metabolic control was improved. 

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