Metabolism

The term 'Metabolism' refers to the absorption, transport, and metamorphosis as well as to the emission of various materials or metabolic products of an organism. These biochemical processes serve to establish the organism as well as to retain it and to produce energy. Thus, these biochemical processes are essential in order to preserve important bodily functions. Basically, the food absorbed by humans is put together by three components: carbohydrates, fat and proteins. The metabolic pathways of these essential components are complex and beyond that closely connected. Important metabolic processes, which play a key role in the production of energy, are the metabolism of carbohydrate and the fat metabolism. Due to protein degradation, especially due to degradation of muscular mass, there can also be provided energy for the body. This process usually proceeds only after all carbohydrate reserves (in the form of glycogen) and fat storages of the body are used up.

The metabolic processes do not always proceed smoothly. If there are pathological variations of these processes, it is said to be a metabolic disorder. These can be of different kinds like a local increase or cluster of certain metabolites, enzyme defects, pathological storage of metabolic products like, for example, haemochromatosis due to which ferric is stored in the organs, or any defect in important transport systems like alack of hormones (e.g. lack of insulin). Characteristic for metabolic disorders is that they can appear with people of any age and that they bear serious consequences with them.

Significant metabolic disorders can cause disorders like a cardiac cycle disorder. Some of those disorders are, for instance, adiposes (obesity) or insulin resistance. Accompanying effects of these two disorders are disorders that often correlate with them like disorders of fat metabolism (for example, varied blood fat value), diabetes mellitus as well as arterial hypertonia. These disorders are different but belong together and can be put together as metabolic syndrome. Apart from substantial alteration of the consistence of the visceral fatmass, genetic factors are important for the development of the metabolic syndrome.

The plasminogenactivator inhabitor type-1 (PAI-1) is a serine protease inhibitor. The primary function of PAI-1 is the fast inhibition of tissue-specific plasminogen-activators. A genetically determined surplus production leads to a reduced fibrinolysis. Additionally, PAI-1 also plays a role in the development of atherosclerosis of patients with a higher triglycerid level, metabolic syndrome or diabetes type II. PAI-1 is produced and discharged by fat cells (adipocytes). Apart from its main function, which is the regulation of coagulation, PAI-1 also participates in the regulation of various processes like cell migration and angiogenesis. Changes in these functions support adiposity. The functional polymorphism PAI-1 4G/5G affects the promotor region of the gene. Therefore, the bond of the transcription regulator is changed and, thus, the transcription rate is raised. The fat tissue of people who are overweight produces a significant higher amount of PAI-1 than the fat tissue of slimmer people. Furthermore, on obesity or other insulin-resistant conditions, the concentration of circulating PAI-proteins is higher. According to further studies, especially TNF-alpha and IL-1B additionally stimulate the PAI-1 production. Thus, a genetic variation in PAI-1 of people with overweight additionally increases the risk of development of the metabolic syndrome and,thus, cardiovascular diseases.

One further, important risk factor is the genetic variation of the PPAR-gamma-2-gene (PPARG). PPAR-gamma-2 is a member of the family of the nuclear hormone receptors. Therefore, it participates in the regulation of the adipocytes differential, the lipidmetabolism and the insulinsensensitivity, which are relevant for the development of diabetes type 2. A polymorphism in the PPAR-gamma-2-gene is associated with an increased susceptibility of type 2 diabetes. The broad consequences of type 2 diabetes (risk for coronary heart disease) speaks for a prevention against diabetes at an early stage. This means an early chance to gain knowledge on the personal risk and to change the food habits early enough to prevent further damage.

The Fatty Acid bindingprotein-2 (FABP2) is a member of the multi gene family which has almost 20 identified members. FABP2, which is experimented in enterocytes only, plays an important role not only in the absorption of long-chained fatty acids in the cell but also in the transport within the cell. Clinically significant is a single mutation in exon 54 of the FABP2-gene, due to which the oxidation of fatty acids and the risk of development of insulin-resistance is immensely increased.
Since fat has -in contrast to proteins and carbohydrates- a very high energy value, people with increased fat intake and lack of exercise have a higher risk to gain overweight and, thus, to get the associated diseases.

Apart from the described protein PPAR-gamma 2 and FABP2 the β2 adrenoreceptor, which is also called ''adrenerger receptor'', plays an important role when it comes to the development of the consequences of obesity. It is coded by the ADRB2-gene. This transmembran protein belongs to the family of the metabotropic G-protein-connected receptors and is activated through binding of its ligand adrenalin. Although the β 2 adrenorreceptors are widely spread, they are mostly localised on cells that have a plane musculature and on the membrane of fat cells. After activation of the receptors due to its ligand it comes -due to the sympathetic nervous system- to relaxation of the plane musculature ( for example the bronchial musculature) or to the discharge of the hormone insulin from the B-cells of the pancreas. Due to the discharge of insulin, not only carbohydrates are activated but also catabolism of fat (lipolyse) is stimulated within the fat cells. Genetic variations of the ADRB2-gene (for example, the punctual mutation Arg16Gly) are especially relevant with obese people since they show a higher risk of developing fat depots and, thus, to gain weight.

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