Biochem - Metabolism (Gluconeogenesis & HMP shunt) Flashcards
Pg. 104-105 in First Aid 2014 Sections include: -Gluconeogenesis, irreversible enzymes -HMP shunt (pentose phosphate pathway)
What are 4 important irreversible enzymes in gluconeogenesis?
(1) Pyruvate carboxylase (2) Phosphoenolpyruvate carboxykinase (3) Fructose-1,6-bisphosphatase (4) Glucose-6-phosphatase; Think: “Pathway Produces Fresh Glucose”
Where is Pyruvate carboxylase found? What reaction does it catalyze?
In mitochondria. Pyruvate => Oxaloacetate
Where is Phosphoenolpyruvate carboxylase found? What reaction does it catalyze?
In cytosol. Oxaloacetate => Phosphoenolpyruvate
Where is Fructose-1,6-biphosphatase found? What reaction does it catalyze?
In cytosol. Fructose-1,6-BP => Fructose-6-P
Where is Glucose-6-phosphatase found? What reaction does it catalyze?
In ER. Glucose-6-P => Glucose
What 2 factors are required for Pyruvate Carboxylase activity? What activates Pyruvate Carboxylase?
Requires biotin, ATP. Activated by acetyl-CoA.
What factor is required for Phosphoenolpyruvate carboxykinase?
Requires GTP
What is a positive versus negative regulator of Fructose-1,6-bisphosphatase?
POSITIVE: Citrate; NEGATIVE: Fructose-2,6-biphosphate
Where does gluconeogenesis primarily occur? What is its purpose?
Occurs primarily in liver; serves to maintain euglycemia during fasting.
Besides liver, where are gluconeogenesis enzymes also found?
Enzyme also found in kidney, intestinal epithelium.
What results from a deficiency of key gluconeogenic enzymes?
Deficiency of the key gluconeogenic enzymes cause hypoglycemia.
What keeps muscle from participating in gluconeogenesis?
Muscle cannot participate in gluconeogenesis because its lacks glucose-6-phosphatase
What do odd-chain fatty acids yield during metabolism? What are the potential metabolic uses of this product?
Odd-chain fatty acids yield 1 propionyl-CoA during metabolism, which can enter the TCA cycle (as succinyl-CoA), undergo gluconeogenesis, and serve as a glucose source
What is the metabolic limitation of even-chain fatty acids, and what causes this?
Even-chain fatty acids cannot produce new glucose, since they yield only acetyl-CoA equivalents.
What are 2 metabolic benefits of the HMP shunt?
(1) Provides a source of NADPH from abundantly available glucose-6-P (NADPH is required for reductive reactions, e.g., glutathione reduction inside RBCs, fatty acid and cholesterol biosynthesis). Additionally, this pathway yields (2) ribose for nucleotide synthesis and glycolytic intermediates.
What is another name for the HMP shunt?
HMP shunt (pentose phosphate pathway)
In brief, how does the HMP shunt yield NADPH? For what type of reactions is NADPH required? Give 3 examples of such reactions.
Provides a source of NADPH from abundantly available glucose-6-P (NADPH is required for reductive reactions, e.g., glutathione reduction inside RBCs, fatty acid and cholesterol biosynthesis)
What sugar does the HMP shunt yield? What are 2 of its metabolic uses?
Ribose for nucleotide synthesis and glycolytic intermediates.
What are the phases of HMP shunt, and where do they occur?
2 distinct phases (oxidative and nonoxidative), both of which occur in the cytoplasm
How much ATP is used versus produced by the HMP shunt?
No ATP is used or produced
What are 4 sites where HMP shunt (pentose phosphate pathway) takes place?
Sites: (1) Lactating mammary glands (2) Liver (3) Adrenal cortex (sites of fatty acid or steroid synthesis) (4) RBCs
Of the phases of HMP shunt, which is reversible versus irreversible?
(1) Oxidative (irreversible) (2) Nonoxidative (reversible)
What are the key substrate and enzyme(s) of the oxidative (irreversible) phase of the HMP shunt? What are the products of this phase?
SUBSTRATE: Glucose-6-Pi; ENZYME: Glucose-6-P dehydrogenase; PRODUCTS: CO2, 2 NADPH, Ribulose-5-Pi
What area the key substrate and enzyme(s) of the nonoxidative (reversible) phase of the HMP shunt? What are the products of this phase?
SUBSTRATE: Ribulose-5-Pi; ENZYME: Phosphopentose isomerase, Transketolases; PRODUCTS: Ribose-5-Pi, G3P, F6P
Which HMP shunt phase reaction is the rate-limiting step? What enzyme(s) is (are) catalyze this step?
Oxidative (irrversible); Glucose-6-P dehydrogenase converts Glucose-6-Pi into CO2 + 2 NADPH + Ribulose-5 Pi
What cofactor is required by the nonoxidative (reversible) reaction of HMP shunt? What enzyme(s) catalyze(s) this?
Requires B1; Phosphopentose isomerase, Transketolases convert Ribulose-5-Pi into Ribose-5-Pi + G3P + F6P
