CT is a 3 year old female who develops signs of hypoglycemia in the early morning unless she is fed during the night. CT eats balanced meals for her age group during the day, with in between meal snacks. She shows no symptoms of hypoglycemia during the day unless she does not snack between meals. Her mother took her to the doctor where a liver biopsy showed that CT had an enlarged liver. The doctor diagnosed CT with an inherited enzyme deficiency of glucose 6-phosphatase.
1. What is/are the role(s) of glucose 6-phosphatase?
1. Glucose 6-phosphatase is an enzyme that hydrolyzes glucose-6-phosphate resulting in the formation of a phosphate group and free glucose.
2. Formation of glucose-6-phosphate is an important step in process of step in gluconeogenesis and glycogenolysis. Therefore plays a key role in the homeostatic regulation of blood glucose levels.
3. Production of glucose 6-phosphate is done in two ways:
a) From glucose b) From glycogen
a) Production of glucose 6-phosphate from glucose:
• Within a cell, glucose 6-phosphate is produced by phosphorylation of glucose. This reaction is catalyzed by the enzyme hexokinase in lower organisms. In higher organisms, enzyme glucokinase is responsible for production of glucose 6-phosphate is produced by phosphorylation of glucose in liver cells.
• One molecule of ATP is consumed in this reaction.
• D-Glucose = Hexokinase α-D-Glucose 6-phosphate
• The process of phosphorylation adds a charged phosphate group so the glucose 6-phosphate cannot easily cross the cell membrane and thus prevent diffusion of glucose out of the cell.
b) Production of glucose 6-phosphate from glycogen
• Glucose-6-phosphate is also produced during glycogenolysis from glucose-1-phosphate. Glucose-1-phosphate is the first product of the breakdown of glycogen polymers.
2. Starting with pyruvate, describe in metabolic detail how a glucose 6-phosphatase deficiency results in impaired gluconeogenesis.
1. Gluconeogenesis is a metabolic pathway that is responsible for the generation of glucose from lactate, glycerol and glucogenic amino acids(non-carbohydrate carbon substrates).
2. Normally in gluconeogenesis, Lactate in the liver, is converted into pyruvate via the enzyme lactate dehydrogenase.
3. Pyruvate is the first designated substrate of the gluconeogenic pathway which is then be used to generate glucose.
4. Lactic acidosis occur due to deterioration of gluconeogenesis.
5. In liver and muscles, Lactic acid is oxidized by NAD+ to pyruvic acid and then converted via the gluconeogenenic pathway to G6P.
6. Accumulation of G6P inhibits conversion of lactate to pyruvate.
7. The lactic acid level rises during fasting as glucose falls.
8. In people with gluconeogenesis, it may not fall entirely to normal even when normal glucose levels are restored.
3. Explain why CT would have an enlarged liver with a glucose-6-phophatase deficiency?
1. Liver enlargement is known as Hepatomegaly. It is due to accumulation of glycogen because of deterioration of glycogenolysis is mainly responsible for enlargement of the liver.
2. In some cases, enlargement of liver is observed in the first few months to develop in fetal life. When a child learn to stand and walk, the hepatomegaly cause the abdomen to bulge out. The liver edge is also below the level of the umbilicus. In such cases, sometimes there is a risk of developing tumors of the liver.
In the presence of adequate glucose 6-phosphatase, postulate how a biotin 4. In the presence of adequate glucose 6-phosphatase, postulate how a biotin deficiency may influence gluconeogenesis?
1. Biotin is a water-soluble B-complex vitamin also known as vitamin B7. Blood sugar and insulin levels decline during Biotin deficiency.
2. In case of biotin deficiency, insulin-producing cells are increased in number as well as size in pancreas.
3. Research reports have concluded that due to biotin deficiency blood sugar level is decreases and thus body promotes mechanisms that increase blood sugar .
4. Biotin acts as a co enzyme that is responsible for production of glucose.
5. Biotin is also responsible for breakdown of glucose for energy and promotes movement of glucose from blood to liver.
6. In liver glucose is converted to glycogen. Glucose is stored in liver in form of glycogen. Researchers recommend biotin diet to recover hypoglycemia
5. How would a deficiency of glucose 6-phosphatase affect the formation of glucose in muscle?
1. In gluconeogenesis, Lactate is produced from pyruvate passes to the liver via the blood. In liver it is converted to glucose. The glucose then travel back to the muscle to fuel the process of Glycolysis in muscles. The deficiency of glucose 6-phosphatase in muscles affect the process of Glycosis and in turn, affect the production of ATP and energy.
2. In liver and muscles, Lactic acid is oxidized by NAD+ to pyruvic acid and then converted via the gluconeogenenic pathway to G6P. Accumulation of G6P inhibits conversion of lactate to pyruvate. The lactic acid level rises during fasting as glucose falls. In people with gluconeogenesis, it may not fall entirely to normal even when normal glucose levels are restored.
6 a What were three “knowledge gaps” you had related to this case that you needed to address before starting this case study?
(NOTE: There are no wrong answers, I am interested in what you needed to know to answer the questions).
For example, someone without a nutrition background may need to look up what hypoglycemia is before answering the questions.
Before answering the question, I have studied the following:
1. Metabolic pathway responsible for hypoglycemia:
As per my study I identified that gluconeogenesis is mainly responsible for Hypoglycemia.
2. The enzyme responsible for hypoglycemia:
Deficiency of glucose 6-phosphatase enzyme is the major reason for hypoglycemia.
3. Involvement of glucose 6-phosphatase in gluconeogenesis
Study the effect of glucose 6-phosphatase deficiency in the metabolic pathway(gluconeogenesis)
4. Effect of hypoglycemia on muscles and liver. The effect of deficiency of glucose 6-phosphatase in muscles (process of glycosis) and ATP production.
5. Effect of biotin deficiency may influence gluconeogenesis and blood sugar level.
6. Mechanism of glucose formation in muscles during deficiency of glucose 6-phosphatase.
2 b) Select one of your ‘knowledge gaps’ and describe specifically what you did to learn more about this issue (i.e., did you look up the information in the textbook, go to the library, search the internet, etc.)
Here I a m explaining the first point: Metabolic pathway responsible for hypoglycemia:
1. Gluconeogenesis is the metabolic pathway, responsible for the generation of glucose .
2. Glucose 6-phosphatase is an enzyme that converts glucose-6-phosphate to a phosphate group and free glucose.
3. In gluconeogenesis, Lactate is converted into pyruvate in the liver.
4. Lactic acid is oxidized to pyruvic acid and then converted to glucose-6-phosphate.
5. Accumulation of glucose-6-phosphate inhibits conversion of lactate to pyruvate.
6. The glucose level falls and lactic acid rises during fasting.
6 c. Identify in detail what you learned by researching your three ‘knowledge gap.’ (NOTE: This can be related to the topic or something else you discovered, such as a helpful web
After extenstive studies, I learned that:
1. Liver enlargement (Hepatomegaly) is due to accumulation of glycogen.
2. When a child learn to stand and walk, the hepatomegaly cause the abdomen to bulge out. Sometimes, there is a risk of developing tumors of the liver.
3. Blood sugar and insulin levels also decline during Biotin(vitamin B7) deficiency.
4. In liver glucose is converted to glycogen. Glucose is stored in liver in form of glycogen.
5. Researchers recommend biotin diet to recover hypoglycemia.