Cho

1- only a very small amount of ingested cho are monosaccharides, most of them are in complex forms like glucogen and starch and cellulose and disaccharides 2-digestion of starch and glycogen starts in the mouth by secretion of salivary amylase that partly digest them to dixterin and few moles of maltose 3-no digestion for cho in stomach due gastric acidity 4-in small intestine pancreatic amylase is secreted to completely digest them to maltose 5- brush border of intestinal mucosa secretes enzymes like maltase , lactase, isomaltase and sucrase that digest disaccharides Maltase and isomaltase ~> 2 glucose Lactase~> glucose and galactose Sucrase~> glucose and fructose 6- uptake of glucose by na / glucose transporter an active transport system 7- there are non digestable carb like dietary cellulose that is made of glucose united linked by b1-4 glucosidic linkages and in human there is no b1-4 glucosidase that can digest such bond

Deficiency in lactase enzyme in the brush border of enterocytes that digest lactose into galactose and glucose

More than three quarters of the adults are lactose intolerant

1- may be congenital ( rare) 2- may be acquired ( common)

Lactose accumulation in intestine 1- increased osmotic pressure: the water will drawn from the tissues ( causing dyhdration) To the large intestine causing diarrhea 2- increased fermentation of lactose by bacteria Leading to production of Co2 gas that cause distension and abdominal cramps

Different sugars have different mechanisms of absorption as glucose and galactose are absorbed by SGLUT -1 ( sodium dependant monosaccharide cotransporter 1 ) and fructose is absorbed by GLUT -5 ( sodium independent monosaccharide transporter 5) and all these are are transported into portal circulation by GLUT -2

Two transport mechanisms Na dependant monosaccharide cotransporter (SGLUT) Na independent monosaccharide transporter (GLUT)

• This is an energy-requiring process • that transports glucose from low glucose concentrations outside the cell to higher concentrations within the cell • The carrier is a sodium-dependent • SGLT -1 is found in the intestinal mucosa (enterocytes) of the small intestine , SGLT-2 is found in proximal tubule of the nephron and contribute to renal glucose reabsortion

family of 14 glucose transporters in cell membranes. (GLUT-1 to GLUT-14 )There are 4 major glucose transporters ,each with a different affinity according to its physiologic role. Normal glucose concentration in peripheral blood is 4-6 mM GLUT-1 Most tissues (brain, Basal uptake of glucose red cells) (-1mM) GLUT-2 Liver. Uptake and release of Pancreatic b cells glucose as glucose (-15 mM). Sensor Upt GLUT-3 Most tissues. Basal uptake (-1 mM) GLUT-4 Skeletal muscle Adipose tissue. Insulin stimulated glucose (-5mM). uptake , stimulated by exercise

1- oxidation • Glyolysis followed by krebs cycle and they are the major pathways • Pentose phosphate pathway and uronic acid pathway and they are minor pathways 2- storage in form of glycogen and fats 3- conversion to important substances • lactose to form milk • fructose to semen • ribose and dehydroxyribose to form RNA AND DNA

Oxidation of glucose to give 2 pyruvate and 6 or 8 ATP ( in case of o2 presence) or 2 lactate and 2 ATP (in case of o2 absence)

Cellular location : cytosol Organ location : in all tissues but it has more physiological importance in • CELLS WITH NO MITOCHONDRIA Eg RBC • CELL WITH FEW MITOCHONDRIA Eg testes and leukocytes • cell with that undergo frequent o2 lack eg sk m during excercise

1- peraparatory phase • named also priming phase • it includes the first 5 enzymtic reactions • 2 ATP are consumed in this phase • it ends by convervion of glucose into 2 glyeroldyhyde 3 p 2- pay off phase • named also energy producing phase • it includes the second 5 enzymtic reactions • it ends by conversion of mentioned to 2 pyruvate and 4 ATP and 2 NADH

حدوتة مصرية

Phosphorylated sugars can’t penetrate the cell membrane as they have no transporter for them thus irreversible phosphorylation of glucokinase to glucose trap them into the cell as cytosolic glucose 6-p thus comitting them to further metabolism in the cell

Both consume ATP AND Mg for their functions Glucokinase Site : Liver and -cells of pancreas. Substrate: only glucose Activity : Its activity is inducible by the presence of high glucose level in the cell. Affinity of glucose :Its Km for glucose is high and operates only when blood glucose level is above 100 mg/dl Functions:In ß cells of pancreas, glucokinase functions as the glucose sensor for insulin secretion inactivation mutations can impair insulin secretion result in maturity onset diabetes of the young ( MODY) In the liver, it facilitates glucose phosphorylation during the well-fed state. Allosteric inhibition: Not inhibited by glucose-6-phosphate Effects of hormones: -Induced by insulin -Inhibited by anti-insulin hormones Effect of food : increased by feeding & inhibited by fasting Hexokinase Site : All tissue cells. Substrate: glucose and other hexoses Activity: It is a constitutive enzyme. Affinity of glucose: It has low Km for glucose i.e., high affinity for glucose. This permits efficient phosphorylation & subsequent metabolism of glucose even when tissue concentrations of glucose are low. Functions: It ensures glucose energy supply for tissues even in fasting states. Allosteric inhibition :Allosterically inhibited by glucose 6-phosphate Eff of hormone: Not affected by hormones Effect of food: Not affected

1- PFK -1 is the rate limiting and controlling enzyme in glycolysis 2- PFK -1 is inhibited by ATP and citrate and activated by AMP 3-Insulin stimulates and glucagon inhibits PFK-1 in hepatocytes by an indirect mechanism involving PFK-2 and fructose 2,6-bisphosphate. F2,6-BP activates PFK-l

There are two types of them Aldolase A : presents in all tissues and split fructose 1,6 bip Aldolase B : in liver and kidney and split fructose 1-p

1- add Pi to its substrate results in production of high phosphate containing compund ( 1-3 biphosoglycerate) 2- reduce NAD TO NADH 3- arsenate inhibits the conversion of glyceraldehyde 3 p to 1-3 biphosphoglycerate by mimiking the p in reaction , the arsenate will let glycolysis go on but no ATP production

• only used in anerobic glycolysis • it re oxidise the NADH TO NAD replenishing the oxidised co enzyme of glyceraldehyde 3p dehydrogenase • without mitochondria and o2 the glycolysis will stop when all the available NAD is reduced to NADH , by reducing pyruvate to lactate and oxidation of NADH lactate dehydrogenase prevents this problem • in aerobic tissues , lactate does not normally form in significant amount except for in where the o2 is poor ( skeletal muscle during excercise ) most ATP IS generated by anerobic glycolysis and lactate production increases ( lactic acid )

• in anerobic conditions, pyruvate is reduced to lactate • lactate formation is obligatory end product of glycolysis in RBCS , parts of retina , skeletal muscles during exercise ~ in aerobic conditions, pyruvate is transported to mitochondria and acts as substrate to two enzymes pyruvate dehydrogenase and pyruvate carboxylase producing actyel CoA and oxaloacetate for krebs cycle ( actyel CoA ~> TCA ~> co2 and +ATP ~> fatty acid synthesis. )

Under anaerobic conditions NADH is re-oxidized to NAD replenishing oxidized coenzyme for glyceraldehyde 3 p dehydrogenase Wash out excess pyruvate which cannot pass membranes.

2 ATP

6 or 8 ATP