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Digestion n Absorption

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At the end of this class, students should beable to know that / the:-

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BioHealth Importance

Knowledge of normal metabolism is essential for an

understanding of abnormalities underlying disease.

  Normal metabolism includes adaptation to periods of 

starvation, exercise, pregnancy, and lactation.

Abnormal metabolism may result from nutritional deficiency,

enzyme deficiency, abnormal secretion of hormones, or the

actions of drugs and toxins.

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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.

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(2) Catabolic pathways, which are involved in the breakdownof 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).

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The mix of carbohydrate, lipid, and protein being oxidizedvaries, 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 constantthroughout the day, since average physical activity increases

metabolic rate only by about 40±50% over the BMR .

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However, most people consume their daily intake of metabolicfuels 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.

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By contrast, if the intake of metabolic fuels is consistentlylower 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.

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Figure: Emaciation.

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In the fasting state glucose must be secured for use by thecentral 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.

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Figure: Outline of the pathways for the catabolism of dietary

carbohydrate, protein, and fat.

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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 deliveredto the tissues.

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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 prot eases and

li  pases aid this process for proteins and fats, respectively.

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The mixture of gastric secretions, saliva, and food, knowncollectively 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.

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The net result is the almost complete conversion of digestiblecarbohydrate to its constituent monosaccharides.

The resultant glucose and other simple carbohydrates are

transported across the intestinal wall to the hepatic portal veinand 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.

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Figure: Transport of glucose,

fructose, and galactose across

the intestinal epithelium.

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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.

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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 responseto 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".

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GLUT3 is found primarily in neurons but also found in theintestine.

GLUT3 binds glucose with high affinity (has the lowest K m of 

the GLUTs) which allows neurons to have enhanced access toglucose 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.

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GLUT5 and the closely related transporter  GLUT7 areinvolved 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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