Chapter 14 ( Glycogen , Gluconeogenesis And HMS ) Flashcards
Rate limiting enzyme of glycogen synthesis ?
Glycogen synthase
Allosteric activator of glycogen phosphorylase and allosteric inhibitor ?
Activator : AMP , Ca
Inhibitor : ATP
In MUSCLES ONLY
Rate limiting enzyme in glycogenolysis ?
Glycogen phosphorylase
By which enzyme the only free glucose is produced directly in glycogenolysis ?
Debranching enzyme by the alpha-1,6 Glucosidase activity
Von Gierke disease ?
Deficient enzyme : Glucose -6- phosphatase
Cardinal features : severe hypoglycemia, hepatomegaly, hyperlipidemia, lactic acidosis, hyperuricemia, short, doll like facies, protruding abdomen and emaciated extremities
Glycogen structure : normal
Pomp disease ?
Deficient enzyme : lysosomal alpha1,4-glucosidase ( acid maltase )
Cardinal features : cardiomegaly
Muscle weakness
Death by 2 years
Glycogen structure : glycogen like material in inclusion bodies
Cori disease ?
Deficient enzyme : debranching enzyme
Cardinal features : mild hypoglycemia and liver enlargement
Glycogen structure : short outer branches , single glucose residue at outer branch
Andersen disease ?
Deficient enzyme : branching enzyme
Cardinal features : infantile hypotonia and cirrhosis
Death by 2 years
Glycogen structure : very few branches especially towards periphery (linear glycogen)
McArdle disease ?
Deficient enzyme : muscle glycogen phosphorylase ( myophosphorylase )
Cardinal features : muscle cramps , weakness on exercise and myoglobinuria , recovery after 15 mins of exercise ( second wind )
Glycogen structure : normal
Hers disease ?
Deficient enzyme : hepatic glycogen phosphorylase
Cardinal features : mild fasting hypoglycemia , hepatomegaly , cirrhosis
Glycogen structure : normal
Cause of hyperuricemia in Von Gierke disease ?
Decreased Pi cause increased AMP which is degraded into uric acid , lactate slows uric acid excretion in the kidney
When does gluconeogenesis represent the only source for glucose ?
After 24 hours of fasting
Substrates for gluconeogenesis ?
Glycerol-3-phosphate
Lactate
Gluconeogenic amino acids
Ketogenic and glucogenic amino acids ?
“PITTT” Phenylalanine Isoleucine Tryptophan Threonine Tyrosine
Requirements of Pyruvate carboxylase ? And its obligate activator
ABC ATP Biotin CO2 Obligate activator : Acetyl-CoA
The key control enzyme of gluconeogenesis ? Its activator and inhibitor ?
Fructose 1,6-bisphosphatase
Activator : ATP ( generated by fatty acid Beta oxidation )
Inhibitor : F2,6P
Why can’t the skeletal muscle serve as source of blood glucose ?
Because of the absence of glucose-6-phosphatase in skeletal muscles
Cori cycle ?
During fasting , Lactate from RBCs is converted in the liver to glucose that can be returned to RBCs or muscles
Alanine cycle ?
Muscles release alanine drlivering both gluconeogenic substrate and an amino group for urea synthesis
In alcoholism what does NADH favor ?
The formation of Lactate from pyruvate Malate from OAA in the cytoplasm Glycerol-3-phosphate from DHAP This effect divert important gluconeogenic structures from entering gluconeogenesis
Inhibitor for alcohol dehydrogenase ?
Fomepizole
Inhibitor of acetaldehyde dehydrogenase ?
Disulfiram
Explain the presence of steatosis in alcoholism ?
Accumulation of NADH and glycerol-3phosphate contributes to lipid accumulation in alcoholic liver disease
What are the major 2 functions of HMS ?
1- NADPH production
2- source for ribose-5-phosphate for nucleotide synthesis
Rate limiting enzyme of HMS ? Its stimulator ? Inhibitor ? Activator ?
Glucose-6-phosphate dehydrogenase
Induced by : insulin
Inhibited by : NADPH
activated by : NADP
The only thiamine enzyme in RBCs ?
Transketolase
Functions of NADPH ?
Biosynthesis
Supply of reduced glutathione to protect against reactive oxygen species
Bactericidal activity in PMN
Defect in Chronic Granulomatous Disease ( CGD ) ? Diagnostic test ? Patients susceptible to which organisms ?
NADPH oxidase is genetically deficient
Diagnostic test : Negative nitroblue tetrazolium test
Organisms : Catalase-positive organisms as S-aureus , E-coli , candida and aspergillus
Defect in methemoglobinemia ? Its ttt ?
Met-Hb reductase is defective
Treated with Methylene Blue ( reductant )
Glutathione structure ?
3 amino acids peptide with Cysteine in the middle
Dangers of reactive oxygen species on RBCs ?
Hemoglobin may precipitate Heinz bodies
Membrane lipids may undergo peroxidation weakening the membrane and causing hemolysis
How RBCs counter reactive oxygen species ?
By glutathione peroxidase/ glutathione reductase system which requires NADPH supplied by HMP shunt in RBCs
Precipitators of hemolytic episodes in G6PD deficiency ?
Certain drugs
Fava beans
Overwhelming infections as pneumonia or infectious hepatitis
When does symptoms of CGD develop in G6PD deficiency patients ?
If the G6PD activity is less than 5% of normal in PMN to generate NADPH for the NADPH oxidase bactericidal system
