Unit 6 - Pentose Phosphate Shunt and Gluconeogenesis

Question 1

where are Shunt enzymes located? what are the 2 most important products?

Answer 1

all in the cytosol (like in glycolysis)

-NADPH and ribose-5-phosphate are most important

Question 2

what are the 2 phases of the shunt? what are the distinguishing features and main products?

Answer 2

1. oxidative phase (first 3 steps, all irreversible)
   - G6P + 2 NADP+ H2O –> 2 NADPH + 2 H+ + CO2
2. nonoxidative phase (next 5 steps, all reversible)
   - Ru5P –> 2 F6P + 1 GAP

Question 3

what is the overall gain and cost of the shunt? why is this so? (assume starting with 3 glucose)

Answer 3

gain 6 NADPH, cost 1 GAP; if starting with 18 C…

• glycolysis would make 6 GAP (18 C)
• oxidative phase gives 3 CO2 (3C) + 3 Ru5P (15 C) + 6 NADPH
• -nonoxidative uses 3 Ru5P to make 1 R5P (5 C) + 2 Xu5P (10 C) to make 2 F6P (12 C) + 1 GAP (3 C)

Question 4

compare and contrast NAD+ (nicotinamide adenine dinucleotide) and NADP+ (“” phosphate)

Answer 4

have same REDOX RXNs, but cannot be converted to each other

• C2 hydroxl O of ribose has H+ in NAD, and phosphoryl group in NADP+ so enzymes can distinguish
• pool of NADPH (primary reductant) is highly reduced state for detox and biosynthesis, but pool of NAD+ (primary oxidant) is in highly oxidized state to push glycolysis and TCA forward

Question 5

where is NADPH used in the SI and liver?

Answer 5

used by cytochrome P450 (ER monooxygenases) to detox xenobiotics

Question 6

what is the purpose of the pentose phosphate pathway in:

• adrenal gland
• liver
• adipose tissue
• testes/ovary
• mammary gland
• SI
• RBC

Answer 6

1. steroid synthesis
2. cholesterol and FA synthesis, plus detox xenobiotics
3. FA synthesis
4. steroid synthesis
5. FA synthesis
6. detox xenobiotics
7. detox ROS

Question 7

what happens if you have G6P dehydrogenase deficiency?

Answer 7

most common human enzyme deficiency

• causes favism (hemolytic anemia, especially if take antimalarial drugs like quinine or chloroquine, or eat high oxidant foods)
• evolutionary advantage b/c it’s better to pay metabolic cost of faster rate of turnover of RBCs than die of malaria

Question 8

what is ribose used for? how is it obtained via the PPS?

Answer 8

info storage (RNA/DNA), E transfer (NTPs), REDOX (NADH/FAD), and enzyme catalysis (CoA)
-run nonoxidative phase in reverse so that F6P --> R5P (don't do oxidative phase, don't get NADPH)

Question 9

what happens to the shunt if cells need both NADPH and ribose?

Answer 9

run oxidative phase of shunt, and convert all Ru5P to R5P

Question 10

what percentage of metabolized glucose goes thru the PPS?

Answer 10

30%

Question 11

where is glucose 6 phosphatase?

Answer 11

liver and (to a small extent) kidney

Question 12

why shouldn’t you go cold-turkey into a low-carb diet?

Answer 12

the gluconeogenesis enzymes are only in moderate levels in the body, so you need to go slowly to build up higher levels (or else get hypoglycemic)

Question 13

what are the 3 “bypasses” to circumvent irreversible glycolytic steps?

Answer 13

bypass I - pyruvate carboxylase + PEPCK (pyruvate –> PEP)
bypass II - FBPase (FBP –> F6P)
bypass III - glucose-6-phosphatase (G6P –> glucose)

Question 14

what are the only AA’s that cannot contribute to gluconeogenesis?

Answer 14

leucine and lysine

Question 15

can ACoA from FA and AA contribute to gluconeogenesis?

Answer 15

no

Question 16

where does gluconeogenesis begin, and why?

Answer 16

mitochondria, b/c that’s where the citric acid cycle and pyruvate carboxylase is
-exception is glycerol, which gets converted to DHAP in cytosol

Question 17

how does the malate/aspartate shuttle contribute to gluconeogenesis

Answer 17

no transport for OAA, but it can exit mitochondria by mal/asp shutting running in reverse

• cytosol: malate or aspartate –> OAA
• mitochondria: OAA –> malate or aspartate
• thru inner mitochondrial membrane: channels for both malate and aspartate

Question 18

what is the cost of gluconeogenesis?

Answer 18

net loss of 4 ATP per round trip

• glucose –> pyruvate = gain 2 ATP
• pyruvate –> glucose = use 2 ATP + 2 GTP (bypass I), use 2 ATP at PGK = 6 ATP

Question 19

what is the Cori cycle?

Answer 19

when ATP demands in muscle exceed capacity of oxidative phosphorylation for generating ATP; make lactate instead (also in RBC)

• lactate carried to liver, converted to glucose, released back into bloodstream
• continues after exercise so glycogen stores are replenished

Question 20

what is the O2 debt?

Answer 20

amt of O2 consumed in liver during rebuilding of muscle glycogen after exercise