[aktorque]

Q NO 1: A 34-year-old female develops moderate hyperglycemia during her first pregnancy and is diagnosed with gestational diabetes mellitus. Her glycemic status improves markedly after delivery. She says that her mother and younger sister both had “high blood sugars” during pregnancy. If this patient’s gestational hyperglycemia is genetically predisposed, this patient is most likely to have decreased activity in which of the following enzymes?


A. Glucokinase
B. Phosphofructokinase
C. Aldolase
D. Pyruvate kinase
E. Enolase
F. Pyruvate carboxylase
G. Lactate dehydrogenase

?????

 

[Haisook]

B. Phosphofructokinase

This is the main rate-limiting enzyme in glycolysis. Decreased activity of this enzyme means more glucose is left alone without undergoing glycolysis.

 

[khanar]

Phosphofruktokinase is allosterically inhibited by Glucose I think :notsure:

 

[vagp86]

B. PFK.. its the major rate limiting enzyme...

 

[aktorque]

I'm sorry folks, that's not the correct answer. The most correct answer is ...

Glucokinase

Why? because,

Glucose is the major stimulant of insulin secretion. After glucose enters the beta cells, it is metabolized by glycolysis, followed by citric acid cycle, which results in the generation of ATP molecules. A high ATP to ADP ratios within the beta cells results in the closure of potassium (KATP) channel, which causes insulin secretion by opening the voltage- dependent calcium channel.
In the beta cell of the pancreas, the first enzyme in the glycolytic pathway is glucokinase, instead of hexokinase the first enzyme of other tissues. Glucokinase converts glucose to glucose 6ophosphate.

Glucokinase has a much higher Km (10 mmol) than hexokinase (0.5 mmol). Further more, glucokinase is less sensitive to allosteric inhibition by its product, glucose 6-phosphate. Glucokinase serves as a major glucose-sensor for the beta cell. An increase in serum glucose leads to increased metabolism of glucose within the beta cells ultimately leading to insulin secretion by the formation of ATP.

The conversion of glucose to glucose-6- phosphate by glucokinase is crucial and rate limiting. Once metabolized to glucose 6-phosphate, glucose is rapidly metabolized in the glycolytic and citric cycle.
Glucokinase defects result in one of the types of maturity-onset diabetes. Inactivating mutations of the glucokinase gene lead to a decrease in the enzymes function, causing decrease in the metabolism of glucose, lesser ATP formation, and diminished insulin secretion.

 

[shaan.medico]

confusion

yes u r rite..
bt can u plz explain how def in same gene present with three different types??

1) DM type 1
2) MODY
3) hyperinsulinemia and hypoglycemia

???

 

[Mondoshawan]

yes u r rite..
bt can u plz explain how def in same gene present with three different types??

1) DM type 1
2) MODY
3) hyperinsulinemia and hypoglycemia

???

It wouldn't... The type of MODY caused by a mutation in the GCK gene is MODY2 - this results in a hyperglycemia (mild if the patient does not load on carbohydrates at meals). In a pregnant woman, it could result in hyperinsulinemia in the fetus, if the the fetus does not have the faulty GCK gene (an autosomal dominant loss-of-fx mutation). DM type 1 is a lack of insulin production because of auto-immune destruction of beta cells. The beta cells in the pancreas of someone with MODY2 are there and can make insulin; they just don't have enough copies of GCK to make enough glucokinase to handle large glycemic loads. I'm not sure if that answered your question...?

 

[shaan.medico]

u said "it wudnt"


bt i like to make u clear tht i havnt said that it causes these states,
i was saying tht glukokinase gene mutation will "PRESENT AS" these three states, and nw i got the answer, thnx to wikipedia.


DM 1 - when there is homozygous gene mutation resulting in complete absence of gen activity.

MODY 2- when there heterozygous loss in mutation, resulting in decr activity of this gene, resulting in incr. in threshold for this enz.


hyperinsulinemia hypoglycemia- heterozygous gain in mutation, resulting in decr threshold for this enzyme.



btw thnx for replying......

 

[hana]

u said "it wudnt"

bt i like to make u clear tht i havnt said that it causes these states,
i was saying tht glukokinase gene mutation will "PRESENT AS" these three states, and nw i got the answer, thnx to wikipedia.

DM 1 - when there is homozygous gene mutation resulting in complete absence of gen activity.

You mean DM1 is due to gene mutation of GK enzyme??
UW, Kaplan and FA say it is due to autoimmune destruction of B CELLS, we can not rely on wiki as our source unless you have other references please share.

 

[shaan.medico]

ITS NOT LIKE THE WAY U ARE THINKING,

I m saying that GLUKOKINASE complete loss of function will preent like a state such as DM 1.... its not like glukokinase gene mutation will cause DM1