At the end of this class, students should be able to know that / the



BioHealth Importance 
Knowledge of normal metabolism is essential for an understanding of abnormalities underlying disease.  Normal metabolism includes adaptation to starvation, exercise, pregnancy, and lactation.

periods of 

Abnormal metabolism may result from nutritional deficiency, enzyme deficiency, abnormal secretion of hormones, or the actions of drugs and toxins.


Metabolism is the term used to describe the interconversion of chemical compounds in the body, the pathways taken by individual molecules, their interrelationships, and the mechanisms that regulate the flow of metabolites through the pathways. Metabolic pathways fall into three categories:

(1) Anabolic pathways, which are those involved in the synthesis of larger and more complex compounds from smaller precursors²eg, the synthesis of protein from amino acids and the synthesis of reserves of triacylglycerol and glycogen. Anabolic pathways are endothermic.


(2) Catabolic pathways, which are involved in the breakdown of larger molecules, commonly involving oxidative reactions; they are exothermic, producing reducing equivalents, and, mainly via the respiratory chain, ATP. (3) Amphibolic pathways, which occur at the "crossroads" of metabolism, acting as links between the anabolic and catabolic pathways, eg, the citric acid cycle (TCA cycle).


The mix of carbohydrate, lipid, and protein being oxidized varies, depending on whether the subject is in the fed or fasting state, and on the duration and intensity of physical work.  The requirement for metabolic fuels is relatively constant throughout the day, since average physical activity increases metabolic rate only by about 40±50% over the BMR.


However, most people consume their daily intake of metabolic fuels in two or three meals, so there is a need to form reserves of carbohydrate (glycogen in liver and muscle) and lipid (triacylglycerol in adipose tissue) in the period following a meal, for use during the intervening time when there is no intake of food.  If the intake of metabolic fuels is consistently greater than energy expenditure, the surplus is stored, largely as triacylglycerol in adipose tissue, leading to the development of obesity and its associated health hazards.


By contrast, if the intake of metabolic fuels is consistently lower than energy expenditure, there are negligible reserves of fat and carbohydrate, and amino acids arising from protein turnover are used for energy-yielding metabolism rather than protein synthesis, leading to emaciation, wasting, and, eventually, death.  In the fed state, after a meal, there is an ample supply of carbohydrate, and the metabolic fuel for most tissues is glucose.


Figure: Emaciation.

In the fasting state glucose must be secured for use by the central nervous system (which is largely dependent on glucose) and the red blood cells (which are wholly reliant on glucose).  Therefore, tissues that can use fuels other than glucose do so; muscle and liver oxidize fatty acids and the liver synthesizes ketone bodies from fatty acids to export to muscle and other tissues. As glycogen reserves become depleted, amino acids arising from protein turnover are used for gluconeogenesis.


Figure: Outline of the pathways for the catabolism of dietary carbohydrate, protein, and fat.


Digestion of Dietary Carbohydrates 
Dietary carbohydrate from which humans gain energy enter the body in complex forms, such as disaccharides and the polymers starch (amylose and amylopectin) and glycogen. The polymer cellulose is also consumed but not digested.  The first step in the metabolism of digestible carbohydrate is the conversion of the higher polymers to simpler, soluble forms that can be transported across the intestinal wall and delivered to the tissues.


The breakdown of polymeric sugars begins in the mouth. Saliva has a slightly acidic pH of 6.8 and contains lingual amylase that begins the digestion of carbohydrates. The action of lingual amylase is limited to the area of the mouth and the esophagus; it is virtually inactivated by the much stronger acid pH of the stomach.  Once the food has arrived in the stomach, acid hydrolysis contributes to its degradation; specific gastric proteases and lipases aid this process for proteins and fats, respectively.


The mixture of gastric secretions, saliva, and food, known collectively as chyme, moves to the small intestine.  The main polymeric-carbohydrate digesting enzyme of the small intestine is -amylase. This enzyme is secreted by the pancreas and has the same activity as salivary amylase, producing disaccharides and trisaccharides.


The net result is the almost complete conversion of digestible carbohydrate to its constituent monosaccharides.  The resultant glucose and other simple carbohydrates are transported across the intestinal wall to the hepatic portal vein and then to liver parenchymal cells and other tissues. There they are converted to fatty acids, amino acids, and glycogen, or else oxidized by the various catabolic pathways of cells.


Figure: Transport of glucose, fructose, and galactose across the intestinal epithelium.


Glucose Transporters 
Glucose transporters comprise a family of at least 14 members. The most well characterized members of the family are GLUT1, GLUT2, GLUT3, GLUT4 and GLUT5.  The glucose transporters are facilitative transporters that carry hexose sugars across the membrane without requiring energy. These transporters belong to a family of proteins called the solute carriers.


GLUT1 is distributed in various tissues. GLUT2 is found primarily in intestine, pancreatic -cells, kidney and liver.  GLUT2 molecules can transport both glucose and fructose. When the concentration of blood glucose increases in response to food intake, pancreatic GLUT2 molecules mediate an increase in glucose uptake which leads to increased insulin secretion. For this reason, GLUT2 is thought to be a "glucose sensor".


GLUT3 is found primarily in neurons but also found in the intestine.  GLUT3 binds glucose with high affinity (has the lowest Km of the GLUTs) which allows neurons to have enhanced access to glucose especially under conditions of low blood glucose. Insulin-sensitive tissues, such as skeletal muscle and adipose tissue, contain GLUT4 whose mobilization to the cell-surface is stimulated by insulin action.


GLUT5 and the closely related transporter GLUT7 are involved in fructose transport. GLUT5 is expressed in intestine, kidney, testes, skeletal muscle, adipose tissue and brain. Although GLUT2, -5, -7, 8, -9, -11, and -12 can all transport fructose, GLUT5 is the only transporter that exclusively transports fructose.


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