Biochemistry Entry of Fructose and Galactose

Home , Galactokinase, Galactokinase deficiency, Galactose, Glyceraldehyde, Hepatic fructokinase

Module : 06 Entry of Fructose and Galactose

Dr. Vijaya Khader Dr. MC Varadaraj

Principal Investigator Dr.S.K.Khare,Professor IIT Delhi.

Paper Coordinator Dr. Ramesh Kothari,Professor UGC-CAS Department of Biosciences Saurashtra University, Rajkot-5, Gujarat-INDIA

Dr. S. P. Singh, Professor Content Reviewer UGC-CAS Department of Biosciences Saurashtra University, Rajkot-5, Gujarat-INDIA

Dr. Charmy Kothari, Assistant Professor Content Writer Department of Biotechnology Christ College, Affiliated to Saurashtra University,

Rajkot-5, Gujarat-INDIA

Metabolism of Carbohydrates Biochemistry Entry of Fructose and Galactose

Description of Module

Subject Name Biochemistry

Paper Name 04 Metabolism of Carbohydrates

Module Name/Title 06 Entry of Fructose and Galactose

Metabolism of Carbohydrates Biochemistry Entry of Fructose and Galactose

METABOLISM OF FRUCTOSE Objectives 1. To study the major pathway of fructose metabolism

2. To study specialized pathways of fructose metabolism

3. To study metabolism of galactose

4. To study disorders of galactose metabolism

Metabolism of Carbohydrates Biochemistry Entry of Fructose and Galactose

Introduction

 Sucrose disaccharide contains glucose and fructose as monomers. Sucrose can be utilized as a major source of energy. Sucrose includes sugar beets, sugar cane, sorghum, maple sugar pineapple, ripe fruits and honey

 Corn syrup is recognized as high fructose corn syrup which gives the impression that it is very rich in fructose content but the difference between the fructose content in sucrose and high fructose corn syrup is only 5-10%.

 HFCS is rich in fructose because the sucrose extracted from the corn syrup is treated with the enzyme that converts some glucose in fructose which makes it more sweet.

 Fructose is a product of sucrose hydrolysis and is probably the second most abundant dietary sugar after glucose

The major pathway of fructose metabolism

1. Fructose is phosphorylated by ATP through the action of two different kinases. Yeast glucokinase forms fructose-6-phosphate. In liver and muscle fructose is phosphorylated by a specific fructokinase yielding fructose-1-phosphoate

Metabolism of Carbohydrates Biochemistry Entry of Fructose and Galactose

a. Fructokinase is found in the liver, kidney and small intestine b. The enzyme has a very low Michalis constant (i.e., a high affinity) for fructose c. The activity is not affected by feeding-fasting cycles or by insulin

2. Phosphofructoaldolase (aldolase B) catalyzes the cleavage of D-fructose-1-phosphate a. Phosphofructoaldolase is an isoenzyme of the glycolytic pathway aldolase b. It is abundant in the liver

3. The fate of D-glyceraldehyde may take several routes a. Phosphorylation to D-glyceraldehyde-3-phosphate and metabolism by the glycolytic pathway or the gluconeogenic pathway b. Oxidation to D-glycerate by an NAD+ linked glyceraldehyde dehydrogenase . D- glycerate may then be converted to L-serine via hydroxypyruvate c. Reduction to glycerol by an NADH+ linked glycerol dehydrogenase, followed by phosphorylation to glycerol-3-phosphate. The latter may be used for gluconeogenesis or triglyceride synthesis

Metabolism of Carbohydrates Biochemistry Entry of Fructose and Galactose

Specialized pathways of fructose metabolism

1. Fructose metabolism in spermatozoa a. Fructose is the major energy source for spermatozoa and is formed from glucose in the seminal vesicle b. The pathway involves reduction of glucose to D-sorbitol and oxidation of the latter to D-fructose

c. The fructose concentration of semen may reach to 10 mM. Most of this is available for the spermatozoal because fructose is utilized sparingly by the other tissues that come in contact with the seminal fluid d. The mitochondria of sperm are the only such organelles to contain lactate dehydrogenase. Because this enzyme is present is present the lactate that is formed by fructolysis can be completely oxidized to CO2 and H2O without the need for a shuttle system to transport reducing equivalents into the mitochondria

2. Sorbitol metabolism in diabetes a. The formation of sorbitol from glucose proceeds rapidly in the lens of the eye and in the Schwann cells of the nervous system b. Sorbitol cannot pass through the cell membrane and in the diabetic, sorbitol levels build up in these cells because the rate of oxidation of sorbitol to fructose is decreased

Metabolism of Carbohydrates Biochemistry Entry of Fructose and Galactose

c. It is thought that the elevated sorbitol concentration causes an increase in osmotic pressure which might be a causative factor in the development of the lens cataracts and the neural dysfunction that occur in diabetes.

Defects in fructose metabolism

1. Essential fructosuria In this case fructose is not converted into fructose-1-phosphate due to the deficiency of enzyme hepatic fructokinase . Restriction of dietary fructose is the remedy

2. Hereditary fructose intolerance

Hereditary fructose intolerance is a genetic disorder characterized by vomiting and hypoglycemia after ingestion of fructose or fructose producing foods (e.g., sucrose, sorbitol)

a. It is an autosomal recessive condition involving a deficiency of fructose-1-phosphate aldolase b. Eating a meal containing fructose causes an accumulation of fructose -1-phosphate in tissues, which is believed to underlie the hepatic and renal damage found in the condition c. Several enzymatic activities are inhibited by high cellular levels of fructose-1- phosphate  Fructokinase: its deficiency leads to frutosemia and fructosuria  Hepatic glycogen phosphorylase: the lack is in part responsible for the postprandial hypoglycemia and glucagon unresponsiveness  Fructose 1,6-diphosphate aldolase: without it gluconeogenesis is blocked, contributing to the postprandial hypoglycemia

3. Consumption of high fructose Fructokinase rapidly converts fructose to frutcose-1-phosphate. The activity of the enzyme aldolase B is relatively less and due to this fructose-1-phosphate accumulates in the cell. This leads to the depletion of intracellular inorganic phosphate levels. The phenomenon of binding of Pi to the organic molecules leads to the less availability of Pi for essential metabolic function and is known as

Metabolism of Carbohydrates Biochemistry Entry of Fructose and Galactose

sequestering of phosphate. Due to the decreased availability of Pi, which happens in overconsumption of fructose the liver metabolism is adversely affected. This includes the lower synthesis of Tap from ADP and Pi. High consumption of fructose over a long period is associated with increase uric acid blood leading to gout. This due to the excessive breakdown of ADP and AMP to uric acid

Metabolism of Galactose

1. Lactose is hydrolyzed to yield galactose and glucose in the small intestine of infants and small children by one form of enzyme, which enters the blood stream from the intestine. An adult form of the enzyme is less active and is missing in many adults, leading to a low tolerance for milk and for milk products containing lactose 2. Galactose is phosphorylated by galactokinase to form galactose-1-phosphate 3. Hexose -1-phosphate uridyl transferase catalyzes the transfer of UDP from UDP- glucose to galactose-1-phosphate, to form UDP-galactose and glucose-1-phosphate 4. An epimerase converts UDP-galactose to UDP-glucose

Metabolism of Carbohydrates Biochemistry Entry of Fructose and Galactose

Disorders of galactose metabolism

A. Classical galactosemia- This is due to the deficiency of the enzyme galactose-1- phophosphate uridyltranferase.

1. It is a rare congenital disease in infants 2. Autosomal recessive disorder 3. An excessive accumulation of galactose is due to inborn errors of galactose metabolism 4. Aldol reductase converts excess galactose into galactitol. Galactitol is associated in the development of cataract 5. Accumulation of galactose 1-phosphate in liver results in the depletion of inorganic phosphate for other metabolic functions 6. Symptoms include loss of weight in infants, jaundice, mental retardation etc. In severe case amino aciduria, albuminuria are also observed 7. Diet deprived of galactose and lactose is the remedy

B. Galactokinase deficiency- In this condition there is an accumulation of galactose in blood and tissues. In this defective enzyme galactokinase responsible for the phosphorylation of galactose will also result in galactosemia and galactosuria. Here again galactose is shunted to the formation of galactitol. Generally galactokinase deficient individuals do not develop hepatic and renal complications

C. Uridine diphosphate galactose-4-epimerase deficiency- It is autosomal recessive disorder. This deficiency prevents the conversion of modified form (UDP-galactose) to another modified form (UDP- glucose). As a result compound associated with galactose processing gets accumulated to toxic levels. Symptoms include cataract, intellectual disability and kidney brain and liver are damaged.

Metabolism of Carbohydrates Biochemistry Entry of Fructose and Galactose