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16 Feb 2024
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Question:
A 5-year-old boy is referred to a geneticist due to recurrent episodes of muscle weakness and fatigue triggered by fasting. Physical exam shows hepatomegaly. Biochemical analysis reveals hypoglycemia, hyperlipidemia, and marked elevation in aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Which enzyme most likely has a decreased activity in this patient?
Options:
A)Glycogen phosphorylase
B)Glucose 6-phosphatase
C)Fructose 1,6-bisphosphatase
D)Phosphofructokinase
E)Acetyl-CoA carboxylase
Revise this
👍
2
Question:
A 5-year-old boy is referred to a geneticist due to recurrent episodes of muscle weakness and fatigue triggered by fasting. Physical exam shows hepatomegaly. Biochemical analysis reveals hypoglycemia, hyperlipidemia, and marked elevation in aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Which enzyme most likely has a decreased activity in this patient?
Options:
A)Glycogen phosphorylase
B)Glucose 6-phosphatase
C)Fructose 1,6-bisphosphatase
D)Phosphofructokinase
E)Acetyl-CoA carboxylase
Hi! This question is focusing on glycogen storage disease. You have an individual with fasting hypoglycemia, hepatomegaly, hyperlipidemia, and an elevation in AST/ALT. Going down the list of possible answers:
A. Glycogen phosphorylase --> enzyme deficient in McArdles Ds- since this enzyme is heavily concentrated in skeletal muscles the symptoms would align to that-- muscle cramps, red urine (myoglobinuria). We don't see that in this question stem.
B. glucose 6- phosphatase --> enzyme deficiency in Von Gierke's Ds- this is an enzyme that should break down our glycogen (glucose stores) via glycogenolysis to make glucose available to our body to use (especially during exercise). Without it, we see that HYPOglycemic reactions during exercise, and a build up of glycogen in the liver and kidneys leading us to see the other issues we see in the question stem. (Correct Answer)
C. Fructose 1,6- bisphosphatase is used in gluconeogenesis (making glucose from other metabolites rather than breaking down glycogen to get glucose). So, if it's impaired, you will see the hypoglycemia episodes, but the affects of the built up glycogen in the liver (hyperlipidemia, AST/ALT elevation, etc) wouldn't be seen. So the presence of those things eliminates this as a correct answer choice.
D. Phosphofructosekinase- rate limiting enzyme in glycolysis. This makes it important for breaking glucose down for metabolites like pyruvate and acetyl coA, and is seen in Tarui Ds. This is another glycogen storage disease. Lack of this enzyme stops conversion of F6P to F16BP. Instead, accumulation of F6P pushes it towards G6P formation that can feed into glycogenesis. Well, now that's a problem because too much glycogen in the muscles leads to muscle cramps and fatigue that usually resolves with rest. But remember, it can still break down glycogen to glucose-- so the hypoglycemic symptoms we see in this stem shouldn't be present.
E. Acetyl CoA Carboxylase - the enzyme involved in FA synthesis. This converts Acetyl CoA to malonyl CoA (using Biotin B7 as a cofactor)-- this has to do with lipid synthesis. It would not cause the issues seen in the stem.
I really hope this helps!!
Hi! This question is focusing on glycogen storage disease. You have an individual with fasting hypoglycemia, hepatomegaly, hyperlipidemia, and an elevation in AST/ALT. Going down the list of possible answers:
A. Glycogen phosphorylase --> enzyme deficient in McArdles Ds- since this enzyme is heavily concentrated in skeletal muscles the symptoms would align to that-- muscle cramps, red urine (myoglobinuria). We don't see that in this question stem.
B. glucose 6- phosphatase --> enzyme deficiency in Von Gierke's Ds- this is an enzyme that should break down our glycogen (glucose stores) via glycogenolysis to make glucose available to our body to use (especially during exercise). Without it, we see that HYPOglycemic reactions during exercise, and a build up of glycogen in the liver and kidneys leading us to see the other issues we see in the question stem. (Correct Answer)
C. Fructose 1,6- bisphosphatase is used in gluconeogenesis (making glucose from other metabolites rather than breaking down glycogen to get glucose). So, if it's impaired, you will see the hypoglycemia episodes, but the affects of the built up glycogen in the liver (hyperlipidemia, AST/ALT elevation, etc) wouldn't be seen. So the presence of those things eliminates this as a correct answer choice.
D. Phosphofructosekinase- rate limiting enzyme in glycolysis. This makes it important for breaking glucose down for metabolites like pyruvate and acetyl coA, and is seen in Tarui Ds. This is another glycogen storage disease. Lack of this enzyme stops conversion of F6P to F16BP. Instead, accumulation of F6P pushes it towards G6P formation that can feed into glycogenesis. Well, now that's a problem because too much glycogen in the muscles leads to muscle cramps and fatigue that usually resolves with rest. But remember, it can still break down glycogen to glucose-- so the hypoglycemic symptoms we see in this stem shouldn't be present.
E. Acetyl CoA Carboxylase - the enzyme involved in FA synthesis. This converts Acetyl CoA to malonyl CoA (using Biotin B7 as a cofactor)-- this has to do with lipid synthesis. It would not cause the issues seen in the stem.
I really hope this helps!!
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