Lecture 15: Pentose Pathway

Question 1

Simple sugars

Answer 1

nrg conversion

Question 2

complex carbos

Answer 2

storage forms of glucose

structural

Question 3

glycoconjugates

Answer 3

carbohydrate units covalently linked to proteins or lipieds

Question 4

Pentose Phosphate Pathway

Answer 4

metabolism of ribose sugars to generate NADPH and provide carbo components of nucleotides

Question 5

PPP does what

Answer 5

reduces 2NADP+ to 2NADPH for each glucose-6P that becomes ribulose-5P

Question 6

NADPH is…

Answer 6

the primary reductant in cells (NAD+ is primary oxidant)

critical in maintaining reduced glutothione that minimizes damage from reactive oxygens

Question 7

PPP also produces…

Answer 7

ribose-5-phosphate

the ribose sugar component of nucleotides

Question 8

Oxidative Phase of PPP

Answer 8

generates NADPH for biosynth pathways and for detox of bad oxygens

Question 9

nonoxidative pahse of PPP

Answer 9

interconverts C3, C4, C5, C6, and C7 monosaccharides to make ribose-5P (nucleotide synth) and regenreated glucose-6P (maintain NADPH production)

Question 10

Key enzymes

Answer 10

G6PD: COMMITMENT STEP (feedback inhibited by NADPH)

Transkeotlase and Transaldolase (carbon shuffle reactions)

Question 11

real life example

Answer 11

Glucose-6P dehydrogenase deficiency: Most common enzyme deficiency in the world

RBCs dont make enough NAPDH to protect against reactive oxygen species (becomes a problem when you’re taking anti-malaria drugs)

Question 12

Overview of PPP

Answer 12

oxidative phase: make NADPH
nonoxidative phase: regenerates G-6P

slide 8

Question 13

G6PD

Answer 13

commitment sep in PPP its next thing ,lactonase, has no other metabolic fate but to be converted for use in this pathway

Question 14

carbon shuffle reactions

Answer 14

regenerate 5 glucose-6P from 6 ribulose-5P

use transketolase and transaldolase enzyme reactions

Question 15

First set of nonoxidative phase reactions

Answer 15

convert 6 ribulose-5P to 4 fructose-P and GAP

Question 16

Second set of nonoxidative phase reactions

Answer 16

convert 4 fructose-P and GAP to 5 glucose-6P to make substrate for the PPP

Question 17

Summary of PPP

Answer 17

SIX glucose-6P (C36) are metabolized to regenerate FIVE glucose-6P (C30)

where do the other 6 Carbons go??? (on another card)

Question 18

where do the other 6 Carbons go???

Answer 18

they are lost as CO2 (6 molecules)

Question 19

Metabolic Flux through PPP shunted in 3 directions

Answer 19

if we need NADPH for biosynth pathways: we recycle the 5 G6Ps

if cells need to replenish nucleotide pools: use the Ribose-5P pool

if ATP levels in the cell are low: 6 G6P enter glycolysis to make ATP

Question 20

Regulation of G6PD activity: High NADP+

Answer 20

activate glucose-6P dehydrogenase

PPP activated to get NADPH

Question 21

Regulation of G6PD activity: High NADPH

Answer 21

inhibit glucose-6P dehydrogenase

activate glycolysis

Question 22

glutathione

Answer 22

protects cells from reactive oxygen species
when oxidized, disulfide bond forms between 2 cysteine residues
we want to keep it in its reduced state (we need NADPH for this)

Question 23

what can increase reactive oxygen species (ROS) in cells

Answer 23

mitochondrial aerobic respiration
drugs
fava beans

usually, NADPH levels can maintain rations of GSH:GSSG at 500:1

Question 24

Cancer Cells

Answer 24

have reduced pyruvate kinase activity so that they can inc flux through PPP and make NADPH

they need to limit ROS like H2O2. they do so by favoring glucose to 2 lactate more than oxidation of glucose even though this means less ATP is made

they also shunt some 6GP into PPP in order to produce NADPH to protect from ROS

Question 25

G6P dehydrogenase deficiency in humans

Answer 25

primaquine treatment for malaria inhibits growth of malaria parasite in RBCs by increasing ROS in RBCs
BUT some people get ill after taking this b/c they have G6PD deficiency b/c the ROS in their RBCs are already higher

Question 26

How might this observation explain the high incidence of G6PD deficiency?

Answer 26

they may have a protective effect against malaria

Question 27

Which observation provides the most direct evidence that G6DP deficiency protects against malaria

Answer 27

People with G6PD deficiency have less sever malaria symptoms after exposure to plasmodium

SEE SLIDE 19!!!!!!!!!!!!!!!

Question 28

Would you need to have a deficiency in G6PD to benefit from fava beans as an anti-malarial agent?

Answer 28

if you take vicine and have deficiency, you will get really sick
you’d have to eat a TON

Question 29

vicine

Answer 29

induces oxidative stress in cells similar to primaquine

found in fava beans