Gluconeogenesis and the Pentose Phoshate Pathway Flashcards
Malate shuttle provides way to transfer reducing equivalents (NADH) from mitochondrion to cytosol
- By means of malate shuttle, _________ produced in mitochondria is made available for this later step in cytosol, where it is low
- A different route is followed when lactate is the precursor
–Since NADH is produced in cytosol by LDH, shuttle unnecessary
–A mitochondrial PEP CK converts __________to ___________
NADH
oxaloacetate; PEP
Bypass #3: Glucose 6-phosphatase
- Five protein components
- Large negative DG; irreversible; enzyme is ________-activated
- Operative only in certain tissues (___________, __________, and ________); in other tissues, pathway stops at glucose 6-phosphate
–Lack enzyme; “want” to keep glucose as Glu-6-P, which cannot exit cell
- Phosphatase activity located on inner face of _________
- Glucose generated is transported out of cell via transporter _______
- What disorder is caused as result of a deficiency in Glu-6-phoshatase?
Mg2+
liver, kidney, small intestine lining
ER
GLUT2
Von Gierke’s (a GSD)
Where does the Pentose Phosphate Pathway Occur? What are the function in each location?
How does Energy Charge regulate pathways?
•Low E.C.
–_________[AMP]
–Glycolysis ______
•High E.C.
–Lots of ___________ present
–Biosynthetic reactions _________
–Gluconeogenesis __________
High
Stimulated
ATP
promoted
stimulated
Fates of Glucose
The Three “Bypass” Steps of Gluconeogenesis
•Bypass steps catalyzed by:
–1)____________________
–2)_______________________
–3________________________
- Here, irreversible steps of glycolysis are being replaced
- Bypass #3 (G6Pase) occurs only in certain tissues:
–______________, ____________, and ____________
•First step occurs in ___________, but rest are in ____________
Pyruvate carboxylase and phosphoenolpyruvate carboxykinase (replace pyruvate kinase of glycolysis)
Fructose 1,6-bisphosphatase (replaces PFK-1)
–Glucose 6-phosphatase (replaces hexokinase)
Liver, kidney and epithelial cells of small intestine
mitochondrion;cytosol.
Pyruvate Carboxylase
- Located in ___________; a _________-dependent enzyme
- Pyruvate is either transported into mitochondrion or produced from _________ there
- Reaction occurs in two phases: (i) _________of biotin, and (ii) transfer of_________ group from _________ to ___________
- CO2 (HCO3- ) must be “activated” through ____________ first
- Absolute requirement for acetyl-CoA, a potent allosteric activator
- A heterotetramer, each subunit contains 4 domains: a _____________ domain (phase 1); a pyruvate carboxylase domain (phase 2); a domain that binds acetyl-CoA; and the domain to which biotin is attached via _________ residue
mitochondrion; biotin
alanine
carboxylation; CO2; carboxybiotin; pyruvate
phosphorylation
biotin carboxylation; pyruvate carboxylase; acetyl-CoA lysine
How is Glycerol Converted to a Glycolytic Pathway Intermediate (DHAP)?
How does Fructose 2,6-bisphosphate regulate pathways?
- Acts mainly in __________
- Under starvation conditions
–What hormone is released?
–F2,6BP levels ___________
–Gluconeogenesis ____________
•In fed state
–What hormone is released?
–F2,6BP levels _______
–Glycolysis_________
liver
Glucagon
Decrease
stimulated (glucose is synthesized)
Insulin released
increase
stimulated
Phase 2 of Pentose Phosphate Pathway
Non-oxidative Interconversion of Sugars
What shuttle transports oxaloacetate from mitochondrion to cytosol?
The Malate-Aspartate Shuttle
PEP Carboxykinase
- Reaction:___________
- Located in _________
- Carries out _________and_________ oxaloacetate to give PEP
- Formation of unstable enol compound (__________) is driven by decarboxylation and is trapped by phosphorylation
–Is step reversible or irreversible?
–carboxylation-decarboxylation sequence is a way of __________pyruvate
Oxaloacetate + GTP → PEP + CO2 + GDP
cytosol
decarboxylation and phosphorylation; PEP
Irreversible
“activating”
The Pentose Phosphate Pathway
•Meets the needs of all organisms for __________, which is used for
–reductive biosynthesis of a number of important biomolecules
- Fatty acids
- Cholesterol and the steroid hormones
- nucleotides
- Neurotransmitters
–Protection against ______________arising from oxidative stress, which is especially important in __________ and ________ and _________
•Produces________, needed for synthesis of _______and ______, as well as the coenzymes ATP, NADH, FADH2 and coenzyme-A
–Especially important in rapidly __________cells such as __________, _________, and __________—also tumors
- Involves two phases: __________ and ___________
- Located in __________
NADPH
reactive oxygen species (ROSs)
erythrocytes; lens;cornea of the eye
ribose-5-phosphate; DNA; RNA
dividing
bone marrow, skin, and intestinal mucosa
oxidative and non-oxidative
cytosol
The Importance of Reduced Glutathione for the Red Blood Cell
- Glutathione exists in two interconvertible forms: 2 GSH (red.) = GSSG (ox.)
- GSH protects against __________; it keeps RBCs in ________state (2 GSH = GSSG)
- GSSG converted to GSH via ___________, which uses ___________as cofactor
- ROSs cause cellular damage; especially harmful to _________
- GSH acts as “___________ buffer”:
–Maintains_________ residues of Hb in reduced state
–Keeps iron in reduced,__________, state
–_____________ peroxides and hydroxyl free radicals
•Otherwise: Hb tetramers-Heinz bodies-hemolysis-hemolytic anemia
ROSs
reduced
Glutathione Reductase; NADPH
RBCs
sulfhydryl
Cys
Fe2+
Detoxifies
How is the lactate that is produced during vigorous exercise dealt with?
•It is converted back to glucose via gluconeogenesis in the liver as part of the Cori Cycle.
The PPP Can also be Utilized to Mainly Produce Ribose Sugars. Process
