Inborn error of metabolism

Question 1

Galactose is a component of?

Answer 1

Structural carbohydrates

Question 2

Glucose and galactose are what type of isomer?

Answer 2

C4 Epimers

Question 3

What type of isomers is glucose and mannose?

Answer 3

C2 Epimers

Question 4

What is an enantiomer?

Answer 4

Two molecules with the same mirror image

Question 5

What is a diastereomer?

Answer 5

Two molecules with different mirror images

Question 6

What is some example of disaccharides?

Answer 6

1) Lactose (Galactose + Glucose)

2) Maltose (Glucose + glucose)

3) Sucrose (Glucose + fructose)

Question 7

How is galactose metabolized?

Answer 7

Lactose (galactosyl b-1,4 glucose), is obtained from milk and it is our major source of galactose

It is breaked down by lactase (b-galactosidase)

1) Galactose is converted to galactose-1-phosphate (via galactokinase and ATP)

2) Galactose-1-phosphate is converted into UDP-galactose (donates galactose units for the synthesis of lactose, glycoproteins and glycolipids), by the addition of UDP-glucose to galactose-1-phosphate (via uridylyl transferase)

3) Glucose-1-phosphate is converted into glucose-6-phos[hate and completes its glycolysis pathway

4) UDP-galactose can be utilized either in lactose of glycogen synthesis

Question 8

What are the disorders of galactose metabolism?

Answer 8

1) Galactosemia

2) Galactosemia

Question 9

Where does galactose metabolism occur?

Answer 9

In the liver

Question 10

Describe galactosemia

Answer 10

1) A deficiency in galactokinase “mild galactosemia”, thus no phosphorylation of galactose leading to its accumulation

2) Galactose-1-phosphate uridylyl transferase deficiency (severe galactosemia)
- galactose-1-phosphate will accumulate and stick in the cell, decreasing the availability of ATP = decrease in energy = increase in AMP = URIC acid, in addition to galactose-1-phosphate being cytotoxic producing liver and neural damage (galactose free dies is the only solution)

• aCCUMULATED GALACTOSE CAN BE SHUNTED INTO SIDE PATHWAYS SUCH AS THAT FOR GALACTITOL PRODUCTION (catalyzed by alditol reductase) as galactose accumulation can also cause cataracts

Question 11

Describe galactokinase deficiency

Answer 11

• Rare autosomal recessive disorder
• Causes elevation in galactose concentrations both in urine and blood, which could lead to cataracts

Question 12

What are the sources of fructose?

Answer 12

1) Disaccharide Sucrose (fructose + glucose)
2) Honey and fruits
- Sucrose to fructose and glucose is catalyzed by sucrase

Question 13

How is fructose metabolized?

Answer 13

1) Phosphorylation via fructokinases found in liver
2) Cleavage of fructose-1-phosphate via aldolase

Question 14

Why is fructose metabolism faster than glucose?

Answer 14

Because the trioses formed bypass the Psosphofrutokinase1 the major rate-limiting step in glycolysis this is in the liver

Question 15

What are the disorders of fructose metabolism?

Answer 15

1) Absence of the key enzymes of fructose metabolism
- Lack of fructokinase

2) Heredity Fructose intolerance (Autosomal recessive)
- Can be due to in a deficiency of fructokinase (no problem as the fructose accumulated by this step will be eliminated renally) or aldolase (causes AMP accumulation = uric acid)

• Treatment is a fructose-free diet

Question 16

Describe galactosemia and heredity frutose intolerance

Answer 16

• When Galactose-1-phosphate or fructose 1-phosphate accumulates, it results in a drop in the level of inorganic phosphate (Pi) and
  therefore, ATP production.
• As ATP falls, adenosine monophosphate
  (AMP) rises. The AMP is degraded, causing hyperuricemia (and lactic acidosis).
• The decreased availability of hepatic ATP affects gluconeogenesis (causing hypoglycemia with vomiting) and protein synthesis (causing a decrease in blood clotting factors)

Question 17

What will happen in the case of abnormal degradation of disaccharides?

Answer 17

Due to the presence of this osmotically active material, water is drawn from the mucosa into the large intestine, causing osmotic diarrhea.
This is reinforced by the bacterial fermentation of the remaining carbohydrate to two- and three-carbon compounds (osmotically active) plus large volumes of CO2 and H2 gas, causing abdominal cramps, diarrhea, and flatulence.