2012-11-27 3&4: Gluconeogenesis; Pentose Pi Pathway Flashcards
Quantitatively, what is the most important gluconeogenesis precursor?
lactate
Where does gluconeogenesis occur?
most: liver
some: kidney
Gluconeogenesis is in many ways just the reverse of glycolysis, but it bypasses some of the enzymes. Which are those?
The non-reversible steps
- pyruvate kinase
- PFK
- hexokinase
Which takes the place of pyruvate kinase in gluconeo?
Where does this occur?
What else (beside enzyme(s)) is required?
What regulates it?
Two steps actually req’d:
- pyruvate—pyruvate carboxylase—>oxaloacetate [mitochondria]
- oxaloacetate—PEP carboxykinase—>PEP [cytosoll]
requires 1 ATP and 1 GTP (respectively); pyruvate carboxylase also requires biotin (B7)
regulated by Acetyl-CoA which signals low glucose
How do you get oxaloacetate across the mito membrane?
in mito: oxaloacetate—malate DH—>malate
in cyto: malate—MDH—>oxaloacetate(—>etc.—>glucose)
What bypasses the PFK-1 rxn in gluconeo?
F-1,6-BP—F-1,6-BPase—>F-6-P
What regulates F-1,6-BPase?
Activate: citrate and ATP
Inhibit: F-2,6-P and ADP (coordinate reg so you don’t do both gluconeo and glycolysis at same time)
When would you do both gluconeo and glycolysis at same time?
to generate heat
What conditions would you expect would favor gluconeogenesis and slow down glycolysis?
Lactate levels: low in a.m.; really high s/p exercise
What conditions would favor gluconeogenesis and slow down glycolysis?
High ATP would do both
high lactate and high mito [NADH,H+] favor gluconeogenesis
What enzyme is used to bypass hexokinase?
glucose-6-phosphatase
What is the Cori Cycle?
Muscle: Glucose—>Lactate
——lactate to liver via blood——
Liver: Lactate—>glucose
——glucose to muscle via blood—
How much ATP does Cori cycle require?
6
Does gluconeogenesis from glycerol require more or less ATP than using lactate or a.a.?
Less b/c glycerol jumps right into G3P with one ATP.
Skips the two other ATP-requiring steps
What steps in gluconeo require ATP?
- pyruvate—pyruvate carboxylase—>oxaloacetate
- oxaloacetate—PEP carboxykinase—>PEP
- 3-PGA—>1,3-BPG
How can you make pyruvate?
from 1) glycolysis and 2) from lactate (via LDH)
What are the possible fates of pyruvate?
i.e. What is the first metabolite it would become going down these various pathways? Via which enzymes?
1) lactate via LDH [in anaerobic resp]
2) acetyl-CoA via PDH [in CAC]
3) oxaloacetate via pyruvate carboxylase [in gluconeogenesis]
What is PDH?
pyruvate DH is a oligomeric protein made up of 3 separate enzymes:
E1 (pyruvate decarboxylase), E2 (dihydrolipoyl transacetylase) and E3 (dihydrolipoyl DH)
It requires five co-factors!
Located in mito
Overall what is the rxn PDH catalyzes?
pyruvate + CoA + NAD+ —PDH—>acetyl-CoA + NADH,H+ + CO2
How is PDH regulated?
inhibited by a protein kinase
—kinase is stimulated by ATP, acetyl-CoA, NADH (makes sense b/c shows you have already done enough glycolysis)
—kinase inhibited by pyruvate, ADP
activated by a protein phosphatase
—in turn activated by Ca2+ (muscle contraction link), also insulin?
What is lactose made of?
galactose + glucose
What is sucrose made of?
fructose + glucose
What is maltose made of?
2 glucoses
What causes galactosemia? Sx?
loss of f(x) in Galactose-1-P uridyl transferase causes galactol to build up
sx = causes galactol build-up in lenses—>cataracts
What causes fructose intolerance?
loss of f(x) in liver aldolase; F1P accumulates causing liver damage
What is G6PDH deficiency?
most common enzymopathy
- affects RBCs ability to make NADPH b/c they can only do so via G6PDH
- only symptomatic during periods of ox. stress (e.g. drugs, foods, infection)
- confers protection against malaria
In which tissues does the pentose phosphate pathway MORE active?
adipose, liver, lact mamm, adrenal cortex, thyroid, testes, RBCs
In which tissues does the pentose phosphate pathway LESS active?
cardiac and skel muscle
Where are disaccharides broken down to hexoses?
the surface of endothelial cells in the intestines
What does the pentose phosphate pathway make?
pentoses, NADPH and ATP
What step in the pentose phosphate pathway makes NADPH?
The first two steps:
- G-6-P—G-6-Pi DH—>P-gluconate
- P-gluconate—P-Gluconate DH—>Ribulose-5-P
—The stoich here is 6 for all involved, so 12 total NADPHs are produced!
What step in the pentose phosphate pathway makes ribose?
The third step:
3. Ribulose-5-P—pentose isomerase–>Ribose-5-P—>—>ribose
What are the major end products of the PP pathway? What is formed along the way?
- synth of ribose-5-Pi (forms NADPH, too)
- conversion back to G-6-Pi (NADPH is formed, too)
- Metabolism to lactate via F6P to G3P (NADPH and ATP formed, too)
If glucose in converted to ribose-5-Pi and all of the! ribose-5-Pi is converted to deoxyribose-5-Pi for! synthesis of DNA…
(a) there will be no NADPH formed
(b) there will be no ATP formed
(c) there will be no ATP nor NADPH formed
(d) both ATP and NADPH will be formed.
B
