METABOLISM OF PROTEINS

INTRODUCTION: The main role of amino acids is in the synthesis of structural and functional proteins. Unlike carbohydrates and fats, there is no storage form of proteins in the body. A 70 kg man has an average protein turnover rate of 400 g per day. This is almost the same amount synthesized, and same amount broken down. The non-essential amino acids are either derived from the diet or synthesized in the body, and the essential amino acids are obtained from the diet. Even if one essential amino acid is deficient, protein synthesis cannot take place.

THE AMINO ACID POOL: The body amino acid pool is always in a dynamic steady state. In an adult, the rate of synthesis of proteins balances the rate of degradation, so that nitrogen balance is maintained.

DIGESTION OF PROTEINS: The dietary proteins are denatured on cooking and therefore more easily digested. All these enzymes are hydrolases (class 3 enzymes) in nature. Proteolytic enzymes are secreted as inactive zymogens which are converted to their active form in the intestinal lumen. This would prevent autodigestion of the secretory acini.

The proteolytic enzymes include: 1) Endopeptidases: These act on peptide bonds inside the protein molecule, so that the protein becomes successively smaller and smaller units. This group includes Pepsin, Trypsin, Chymotrypsin, and Elastase.

2) Exopeptidases, which act at the peptide bond only at the end region of the chain. This group includes: 2-A. Carboxypeptidase acts on the peptide bond only at the carboxy terminal end on the chain. 2-B. Aminopeptidase, which acts on the peptide bond only at the amino terminal end on the chain.

The digestion of protein is effected by enzymes in: A) Stomach B) Pancreas and C) Intestinal cells

GASTRIC DIGESTION OF PROTEINS: In the stomach, hydrochloric acid is secreted. It makes the pH optimum for the action of pepsin and also activates pepsin. The acid also denatures the proteins.

1. Rennin: Rennin otherwise called Chymosin, is active in infants and is involved in the curdling of milk.

2. Pepsin: It is secreted by the chief cells of stomach as inactive pepsinogen. The conversion of pepsinogen to pepsin is brought about by removal of 44 amino acids from the N-terminal end, by the hydrochloric acid. The optimum pH for activity of pepsin is around 2. Pepsin is an endopeptidase. Pepsin catalyses hydrolysis of the bonds formed by carboxyl groups of Phe, Tyr, Trp and Met. By the action of pepsin, proteins are broken into proteoses and peptones.

PANCREATIC DIGESTION OF PROTEINS: The optimum pH for the activity of pancreatic enzymes about pH 8 is provided by the alkaline bile and pancreatic juice. The secretion of pancreatic juice is stimulated by the peptide hormones, Cholecystokinin and Pancreozymin. Pancreatic juice contains the important endopeptidases, namely Trypsin, Chymotrypsin, Elastase and Carboxypeptidase. These enzymes are also secreted as zymogens that is trypsinogen, chymotrypsinogen and pro-elastase, so that the pancreatic acinar cells are not autolysed. All the three are serine proteases, that is to say, the active centers of these enzymes contain serine residues.

RELATED;

1.  DIGESTION OF CARBOHYDRATES

2.  METABOLISM AND METABOLIC DISORDERS

3.  BIOCHEMISTRY

TREATMENT OF OBESITY

INTRODUCTION: It is said that the developed world is experiencing an “epidemic of obesity.” This statement is based on statistics showing that in the USA, for example, 30–40% of the population is above optimal weight and that the excess weight (especially abdominal fat) is often associated with the metabolic syndrome and increased risks of cardiovascular disease and diabetes. Cardiacdisease: Diabetes

Since eating behavior is an expression of endocrine, neurophysiologic, and psychological processes, prevention and treatment of obesity are complex. It is not surprising that there is considerable scientific and financial interest in developing pharmacologic therapy for the condition. Although obesity can be defined as excess adipose tissue, it is currently quantitated by means of the body mass index (BMI), calculated from BMI = weight (in kilograms)/height² (in meters). Using this measure, a normal BMI is defined as 18.5–24.9; overweight, 25–29.9; obese, 30–39.9; and morbidly obese (ie, at very high risk), ≥ 40.

Some extremely muscular individuals may have a BMI higher than 25 and no excess fat; however, the BMI scale generally correlates with the degree of obesity and with risk. Although the cause of obesity can be simply stated as energy intake (dietary calories) exceeding energy output (resting metabolism plus exercise), the actual physiology of weight control is extremely complex, and the pathophysiology of obesity is still poorly understood. Many hormones and neuronal mechanisms regulate intake (appetite, satiety), processing (absorption, conversion to fat, glycogen, etc), and output (thermogenesis, muscle work). The fact that a large number of hormones reduce appetite might appear to offer many targets for weight-reducing drug therapy, but despite intensive research, no available pharmacologic therapy has succeeded in maintaining a weight loss of over 10% for 1 year. Furthermore, the social and psychological aspects of eating are powerful influences that are independent of or only partially dependent on the physiologic control mechanisms. In contrast, bariatric (weight-reducing) surgery readily achieves a sustained weight loss of 10–40%. Furthermore, surgery that bypasses the stomach and upper small intestine (but not simple restrictive banding) rapidly reverses some aspects of the metabolic syndrome even before significant weight is lost. However, even a 5–10% loss of weight is associated with a reduction in blood pressure and improved glycemic control. 

PHARMACOTHERAPY: Orlistat is the only non-amphetamine drug currently approved in the United States for the treatment of obesity. Clinical trials and phase 4 reports suggest that orlistat is modestly effective for the duration of therapy (up to 1 year) and is probably safer than the amphetamine mimics. However, it does not produce more than a 5–10% loss of weight. Sibutramine was marketed for several years but was withdrawn because of increasing evidence of cardiovascular toxicity. Lorcaserin received intense study through 2010 and was submitted for approval to the FDA, but this was denied on the basis of considerations of inadequate safety and effectiveness.

Because of the redundancy of the physiologic mechanisms for control of body weight, it seems likely that polypharmacy targeting multiple pathways will be needed to achieve success.

RELATED;

1. OBESITY  

2. DISORDERS OF METABOLISM

3.  MEDICAL CONDITIONS

REFERENCES