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Biochemistry Video 21

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What is the deficiency enzyme, cardinal clinical features, and glycogen structure in von Gierke’s disease?
Glucose 6 Phosphate, severe hypoglycemia, hepatomegaly, hyperlipidemia, and the glycogen structure is normal
What is the deficiency enzyme, cardinal clinical features, and glycogen structure in Pompe’s disease?
Lysosomal alpha 1,4 glucosidase, cardiomegaly, muscle meakness, death by 2 years, the glycogen structure will be glycogen like material in inclusion bodies
What is the deficiency enzyme, cardinal clinical features, and glycogen structure in Cori’s disease?
Glycogen debranching enzyme, mild hypoglycemia (we still have gluconeogenesis), and hepatosplenomegally (glycogen cannot be broken down all the way), the glycogen structure is short outer branches with a single glucose residue at the outer branch
What is the deficiency enzyme, cardinal clinical features, and glycogen structure in Andersen’s disease?
Branching enzyme, osmotic problems cause hypotonia, cirrhosis, and death by age 2, the glycogen structure is that it will have long nonbranched strands of glycogen
What is the deficiency enzyme, cardinal clinical features, and glycogen structure in McArdle’s disease?
Muscle glycogen phosphorylase, muscle cramps and weakness on exercise (not due to lactic acid because you due not have the gluose to perform glycolysis to get the lactate), and the glycogen structure is normal
What is the deficiency enzyme, cardinal clinical features, and glycogen structure in Hers’ disease?
Hepatic glycogen phosphorylase, muld fasting hypoglycemia, hepatomegaly, cirrhosis
What is a good keyword for remembering Pompe’s disease?
Pompe and pump (the heart is a pump and therefore pompe effects the pump)
What is a good way of remembering McArdle’s and Hers’ deaseases?
M in McArdle’s is for MUSCLE .... H in Hers’ is for HEPATIC
Why does von Gierke’s have a severe hypoglycemia, whereas some others had mild hypoglycemia?
Glucose 6 phosphatase is used in both glycogenolysis and gluconeogenesis, all of the other disease only dealt with glycogen issues.
What are the three irreversible steps of glycolysis?
Glucose to glucose 6P via glucokinase⬦⬦ Fructose 6P to Fuctose 1,6-bisP via PFK-1⬦⬦⬦. PEP to pyruvate
What are the necessary cofactors for all carboxylases?
ATP, biotin, and Carbon dioxide
What is the most complicated step of gluconeogenesis?
Conversion of pyruvate to PEP
What are the steps in the conversion of pyruvate to PEP?
Pyruvate to OAA via pyruvate carboxylase to malate via malate dehydrogenase which goes through the malate shuttle to the cytoplasm and then is converted back to OAA via malate dehydrogenase which is then converted to PEP via PEPCK
What is one unique feature about PEPCK?
It is induced by glucagons and cortisol. This is much like the induction of glucokinase by insulin
What enzyme converts fructose 1,6 bisP to Fructose 6P?
Fructose 1,6 bisphosphatase
What converts glucose 6P to glucose?
Glucose 6P
What is the significance of Acetyl CoA in gluconeogenesis?
It provides energy for the process and triggers the process via pyruvate carboxylase
What can all carboxylases be though of as?
ABC enzymes
What does pyruvate carboxylase do?
Converts pyruvate to OAA
What does PEPCK do?
Converts OAA to PEP
What is the key limiting step in gluconeogenesis?
PEPCK
What does PEPCK require?
GTP and it is induced by glucagon
How is Fructose 1,6 Bisphosphate regulated?
When glucagons is present it inhibitsPFK-2 and the production of fructose 2,6 bisphosphate. This defieciecy activates Fructose 1,6 bisphosphate⬦⬦⬦.. locally, ATP inhibits PFK-1 and stimulates fructose 1,6 bisphosphatase
What are the three sources of gluconeogenesis?
Alanine, Lactate, and glycerol 3P
What enzyme is reguired to start alanine in the gluconeogenesis process?
Alanine transaminase
What are the two amino acids that cannot create glucose through gluconeogenesis?
Leucine and lysine
How is NADPH produced?
Glucose 6P goes through two dehydrogense reactions to form two NADPH moleducles. First glucose 6P is converted to 6-phosphogluconate via glucose 6P dehydrogenase, then 6-phosphogluconate is converted to Ribulose 5P by another dehydrogenase. Both of these reaction produce nADPH
What are NADPH molecules used for?
Fatty acid synthesis.
What is the significance of the first half of the HMP shunt?............... second half?
First half = production of NADPH⬦⬦⬦. Second half = production of Ribose 5P
What is ribose 5P used for
Nucleotide synthesis
What is the significance of transketolase (TPP)?
It is a thiamine requiring enzyme that is used to test the thiamine levels in people, such as alcoholics who are suspected to have a deficiency. It is also important in the interconversions between certain glycolytic intermediates and ribose 5P
What are the glycolytic intermediates that can it converted to ribose 5P?
Fructose 6P and glyceraldehydes 3P
For what is NADPH used in the liver?
Synthesis of fatty acids, cholesterol, and nucleotides
For what is NADPH used in the neutrophil?
It will oxide oxygen to make free radicals which will be used to kill bacteria
For what is NADPH used for in red cells?
What is the result of a lack of NADPH in erythrocytes?
The free radiacals will not be neutralized and this will damage the membrane, resulting in hemolytic anemia, and it will also denature the hemoglobin resulting in Heinz bodies
What are the two antioxidant molecules used in the utilization of NADPH?
Glutathione and selenium. Glutathione goes from it’s reduced to oxidized state via glutathione peroxidase, resulting in a neutralized free radical. Selenium is a required cofactor of glutathione peroxidase
What is the enzyme that takes the electrons from MADPH and gives thenm to glutathione?
Glutathione reductase
What is the problem in G6PD deficiency?
You have a deficiency in Glucose 6 Phosphate dehydrogenase and thus you are not able make NADPH. If you cannot make NADPH you cannot reduce the glutathione which therefore cannot neutralize the free radicals. Thus there are many free radicals in the red blood cells which are able to destroy the cells
When would you see the hemolytic anemia associated with G6PD deficiency?
Anytime the body is under oxidative stress. The three classic examples are during and infrection, when taking certain drugs, and when eating FAVA BEANS
What enzyme in the neutrophils creats the free radicals which kill bacteria?
NADPH oxidase
In summary, what are the two important products of the HMP shunt?
NADPH and ribose 5P
What are the important enzymes of the HMP shunt?
Glucose 6 Phosphate Dehydrogenase and transketolase (which requires thiamine

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