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BIOCHEMICAL BASIS FOR HEREDITARY METABOLIC DISEASES - MINI REVIEW

The understanding of IEM is quite difficult, especially while we still cannot fully visualize the metabolism of the human organism as a whole and the connections that exist among the various metabolic reactions, which are crucial in the maintenance of the basic functions of our body.

Metabolism is basically energy production and consumption, obeying certain priorities. Energy is needed primarily for the basal rate of metabolism, which is the energy spent by an individual at rest and in an absorptive state for the normal corporal functions such as breathing, blood flow and maintenance of muscle integrity. The thermal response to alimentary ingestion may represent 5 to 10% of the total energy expenditure for the body. Finally, physical activity provides largest variation in energy expenditure, with a highly active individuals energy expenditure being up to 100% greater than the basal rate of metabolism.

The largest deposits of energy in the organism are glycogen and the triglycerides and there are two priorities during fasting: (1) the maintenance of plasma glucose levels for cerebral metabolism and other tissues that request glucose and (2) the need to mobilize fatty acids from lipid storage and ketone bodies from the liver so as to liberate energy for all other tissues. In the absence of food, plasma glucose, amino acid and triglyceride levels drop, causing a decline in insulin secretion and an increase in glucagon liberation. The low insulin/glucagon ratio and the low availability of circulating substrates create a catabolic state during the period of nutrient deprivation, characterized by triglyceride, glycogen and protein degradation.

The use of energy by our organism and the metabolism during fasting mentioned above refer to healthy adults. In children in a growth phase and/or during an infection, there is a significant increase in the basal rate of metabolism. When there is an IEM in a child with an infection, we may imagine the profound metabolic alterations that occur and understand the gravity of metabolic decompensation, with its high mortality and great difficulty in treatment.

All metabolic events are driven by enzymes that are catalytic proteins and their main function is to increase the speed of reactions, without being altered during that process. The enzymes possess a highly specific active site that links to one or some specific substrates and catalyzes only one type of chemical reaction. Some enzymes associate with a co-factor (metallic ions or coenzyme) needed for the enzyme activity.

Most IEM are a consequence of enzyme deficiencies. In glycogen storage disease Type I, for example, there is an inability to liberate glucose from the liver, neither as a product of glycogenolysis nor gluconeogenesis. Thus, accentuated hypoglycemia occurs. During fasting, the humoral response to hypoglycemia provokes phosphorylase activation and hepatic glycogenolysis. As there is no glucose liberation, glycolysis continues with production of great amounts of piruvate and consequently lactate. The elevation of glycerol, acetyl-coenzyme A and nicotinamide adenine dinucleotide (NADH) levels generated by the increased flow in the glycolytic pathway contribute to the increase in triglyceride and cholesterol synthesis. The glucagon stimulus mobilizes outlying reserves of fat, elevating the circulating levels of free fatty acid. Therefore, innumerable metabolic alterations occur as a consequence of enzyme deficiency and obviously in the case of a child in a growth phase and with a larger number of viral or bacterial infections, the control of these disturbances is worse.

CONCLUSION

IEM are frequently underestimated by the doctor in neonatal and intensive care units of national health clinics or in private clinics. The increase in the rate of identification of these disorders is directly related to clinical judgement and the habit of thinking of those diseases not as rarities but as possibilities, in the light of cases that cannot be explained by more familiar physiopathologies. From this step forward, advances in knowledge and biochemical techniques will really be able to increase the rate of diagnosis.

Source=http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1516-31801999000600006

Metabolic Pathways

The metabolic pathway is a series of chemical reactions that occur within a cell. Within each of these pathways, one chemical is transformed into another chemical through a series of steps. These reactions are catalyzed by enzymes and will often require vitamins and minerals in order to function properly.

One of the first studies of metabolic pathways was done by a British physician named Archibald Garrod in 1909. It was discovered that the most important metabolic pathways for humans are glycolysis—the first pathway discovered— Krebs cycle, oxidative phosphorylation and gluconeogenesis. The collection of all the pathways within the human body is called the metabolic network, and this determines the physiological and biochemical properties of a cell.

Enzymes are considered to be very important to they body metabolic pathway. They act as catalysts in various chemical reactions that occur in the body cells. Enzymes convert substrates into various molecules or products. Since enzymes are selective and will only catalyze a few chosen reactions, the set of enzymes made in a cell determines which metabolic pathways occur in that cell. Enzyme activity can be affected by other molecules; inhibitors will decrease their activity, while activators will increase it.
The body metabolism is divided into two phases: anabolism and catabolism. Anabolism uses energy to construct the components of a cell, such as proteins, whereas catabolism involves the breakdown of organic matter. The result of this metabolic process may either be stored by the cells or used to initiate another metabolic pathway. The metabolic pathway and its activities will depend on other factors as well, including the temperature and the chemical environment, also known as the pH level.

The metabolic pathway is usually believed to travel in one direction, and it is composed of a series of chemical reactions that are connected to each other. These processes allow living organisms to grow and adapt to their environment. The metabolic process will also determine which substances are nutritious and which ones are poisonous. The speed of metabolism in an organism is also known as the metabolic rate.

Other metabolic pathways that occur in most living organisms include fatty acid oxidation and the urea cycle. In humans, the urea cycle takes place primarily in the liver, and it involves the production of urea from ammonia. Fatty acid oxidation is the process in which fat molecules are broken down into free fatty acids and monoglycerides.

source=http://www.wisegeek.com/what-is-the-metabolic-pathway.htm

Dr Archibald Edward Garrod

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