Chapter 14: Glycogen, Gluconeogenesis, and the Hexose Monophosphate Shunt (continued) Flashcards
What is the normal function of lysosomal α1,4 glucosidase?
enzyme normally resides in the lysosome and is responsible for digesting glycogen-like material accumulating in endosomes
Why is Pompe’s disease similar to Tay Sachs or I cell disease?
indigestible substrates accumulate in inclusion bodies
What is another name for lysosomal α1,4 glucosidase?
acid maltase
What is another name for McArdle’s disease?
myophosphorylase deficiency
Why is there amelioration of symptoms for McArdles when one drinks sucrose containing drinks.
dietrary glucose increases glucose in body
What is another name for Hers disease?
hepatic glycogen phosphorylase deficiency
Why is Hers disease usually a mild disease?
because gluconeogenesis compensates for the lack of glycogenolysis
What are important substrates for gluconeogenesis?
- glycerol 3-phosphate
- lactate (from anaerobic glycolysis)
- gluconeogenic amino acids (protein from muscle)
What are the ketogenic amino acids?
leucine and lysine
List the ketogenic and glucogenic amino acids.
phenylalanine
tyrosine
tryptophan
isoleucine
threonine
List the glucogenic amino acids.
An Aggrieved Grinch Validated Garfield Gratefully; And Portentiously Atrocious Mayors Headbutted Carcinogenic Slaves Tactlessly.
asparagine, alanine, glycine, valine, glutamine, glutamate, arginine, proline, aspartate, methionine, histidine, cysteine, serine, threonine
Can dietary fructose and galactose be converted to glucose?
yes; they can be converted to glucose in the liver
Is it possible to convert acetyl CoA to glucose?
no; exceptions are odd number carbon fatty acids which yield a small amount of propionyl CoA that is gluconeogenic
Draw out the steps in gluconeogenesis.
Alanine is converted to pyruvate by what enzyme?
alanine aminotransferase ALT or GPT (serum glutamic-pyruvic transaminase)
Glycerol 3 phophate is oxidized to DHAP via what enzyme?
glycerol 3 phosphate dehydrogenase
What are the 4 important enzymes that are req’d to catalyze reactions in gluconeogenesis?
- pyruvate carboxylase
- PEPCK phosphoenolpyruvate carboxykinase
- fructose 1,6 bisophosphatase
- glucose 6-phosphatase
How can OAA leave the citric acid cycle?
It can’t leave the mitochondria but is reduced to malate that can leave via the malate shuttle in the cytoplasm, then
malate re-oxidized to OAA
What vitamin does pyruvate carboxylase require?
biotin B7
Pyruvate carboxylase is activated by what? What is the obligate activator?
acetyl CoA (from β-oxidation) is the obligate activator
What is PEPCK induced by?
glucagon and cortisol
Where is PEPCK found in the cell?
cytoplasm
What is the key control point enzyme of gluconeogenesis?
fructose 1,6 bisophosphatase
Phosphatases oppose what types of enzymes?
kinases
Fructose 2,6 bisphosphate is produced by what enzyme?
PFK-2
PFK2 is activated by what hormoe? Inhibited by what hormone?
PFK-2 activated by insulin
PFK-2 inhibited by glucagon
Where is glucose-6-phosphatase found in the cell?
in the lumen of the ER
How does glucose-6-phosphate leave the cell?
G6P is transported into the ER and free glucose is transported back into the cytoplasm from which it leaves the cell
What is the only organ glucose-6-phosphatase is found in?
the liver
What is the major gluconeogenic amino acid?
alanine
What are 2 major causes of biotin deficiency?
raw egg whites (avidin)
biotinidase deficiency (rare)
or
long term home TPN
Symptoms of biotin deficiency?
- alopecia
- bowel inflammation
- muscle pain
- scaly dermatitis
- waxy pallor
- acidosis (mild)
Acetyl CoA from FA cannot be converted to glucose but can be converted to what energy source as an alternative fuel for cells, including the brain?
ketone bodies
What are the 2 mitochondrial enzymes that use pyruvate?
pyruvate carboxylase
pyruvate dehydrogenase
What is the Cori cycle?
When, in the fasting state, lactate from RBCs (and possibly exercising sk. muscle) is converted in the liver to glucose that can be returned to the RBC or muscle
What is the alanine cycle?
slightly different version of the cori cycle in which muscle releases alanine, delivering both a gluconeogenic substrate (pyruvate) and an amino group for urea synthesis
What are reasons that patients who abuse alcohol are susceptible to hypoglycemia?
in addition to poor nutrition and the fact that alcohol is metabolized to acetate (acetyl-CoA) high amounts of cytoplasmic NADH formed by alcohol dehydrogenase and acetaldehyde dehydrogenase interfere with gluconeogenesis
What are metabolic products that high amounts of NADH favor?
Formation of:
1. lactate from pyruvate
2. malate from OAA in the cytoplasm
3. glycerol 3-phosphate from DHAP
Draw the pathway of alcohol metabolism.
Refer to diagram on page 215
What is hepatic steatosis?
fatty degeneration of liver tissue
Accumulation of what products in the liver may contribute to lipid accumulation?
cytoplasmic NADH and glycerol 3-P
Pathology of hepatic steatosis?
- Free fatty acids released from adipose in part enter the liver where B-oxidation is very slow (high NADH)
- In presence of high glycerol 3-P, fatty acids are inappropriately stored in liver as triglyceride
Why can alcohol consumption after extreme exercise lead to light headedness, and muscle cramping?
- Because NAD is req’d by LDH to oxidize lactate to pyruvate; however much of available NAD is being used for ethanol metabolism and is unavailable for lactate oxidation.
- Result is metabolic acidosis and hypoglycemia
What does HMP shunt stand for?
hexose monophosphate pathway
Another name for the HMP shunt pathway?
PPP pathway or pentose phosphate pathway
Where does the HMP Shunt take place in the cell??
in the cytoplasm of all cells
What is the purpose of the HMP shunt? (What are its 2 major functions?
- NADPH production
- source of ribose 5-phosphate for nucleotide synthesis
Is the change of G6P to ribulose 5-P in the HMP shunt reversible or irreversible?
irreversible
What is the rate limiting enzyme in the first part of the pathway of the HMP shunt?
G6PDH glucose 6-P dehydrogenase
What hormone is G6PDH induced by?
insulin
What is G6PDH inhibited by?
NADPH
What is G6PDH activated by?
NADP
Draw out an abbreviated diagram of the HMP shunt.
Refer to diagram page 216
What is a major function of ribose 5-P?
for nucleotide synthesis
Transketolase requires what B vitamin?
thiamine (B1)
What are the enzymes in metabolism that require thiamine?
PDH
transketolase
α-ketoglutarate
What are major functions of NADPH?
- biosynthesis (fatty acids, cholesterol, nucleotides)
- maintenance of a supply of reduced glutathione to protect against reactive oxygen species (ROS)
- bactericidal activity in polymorphonuclear leukocytes (PMN)
Create a diagram on the main function of the HMP shunt and resultant NADPH function in the liver.
Create a diagram on the main functions of the HMP shunt in the neutrophil.
Create a diagram on the main function of the HMP shunt on the erythrocyte.
Where are diets of fava beans common? What countries?
Mediterranean countries (Greece, Italy, Spain, Portugal, Turkey)
What is favism?
Severe hemolysis caused by exacerbation of symptoms associated with G6PDH deficiency
What are some symptoms of favism?
pallor, hemoglobinuria, jaundice, and severe anemia 24 - 48 hours after ingestion
What is the major cause of CGD?
genetic deficiency of NADPH oxidase in the PMN
Which infections are patients with CGD susceptible to?
infections by catalase-positive organisms:
S. aureus,
Klebsiella,
E coli,
Candida,
Aspergillus
What test helps to confirm CGD?
a negative nitroblue tetrazolium test
Why are those with G6PDH less susceptible to infection by certain parasites like plasmodium?
because many of these parasite are deficient in antioxidant mechanism making them susceptible to O2 radicals
In G6PDH deficiency, the ability of erythrocytes to detoxify O2 radicals is impaired
In turn, the accumulation of these radicals in erythrocytes in G6PDH def gives protection against malaria
What is the inheritance pattern of those with G6PDH deficiency?
X-linked recessive
