Lecture 15: Pentose Pathway Flashcards
Simple sugars
nrg conversion
complex carbos
storage forms of glucose
structural
glycoconjugates
carbohydrate units covalently linked to proteins or lipieds
Pentose Phosphate Pathway
metabolism of ribose sugars to generate NADPH and provide carbo components of nucleotides
PPP does what
reduces 2NADP+ to 2NADPH for each glucose-6P that becomes ribulose-5P
NADPH is…
the primary reductant in cells (NAD+ is primary oxidant)
critical in maintaining reduced glutothione that minimizes damage from reactive oxygens
PPP also produces…
ribose-5-phosphate
the ribose sugar component of nucleotides
Oxidative Phase of PPP
generates NADPH for biosynth pathways and for detox of bad oxygens
nonoxidative pahse of PPP
interconverts C3, C4, C5, C6, and C7 monosaccharides to make ribose-5P (nucleotide synth) and regenreated glucose-6P (maintain NADPH production)
Key enzymes
G6PD: COMMITMENT STEP (feedback inhibited by NADPH)
Transkeotlase and Transaldolase (carbon shuffle reactions)
real life example
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)
Overview of PPP
oxidative phase: make NADPH
nonoxidative phase: regenerates G-6P
slide 8
G6PD
commitment sep in PPP its next thing ,lactonase, has no other metabolic fate but to be converted for use in this pathway
carbon shuffle reactions
regenerate 5 glucose-6P from 6 ribulose-5P
use transketolase and transaldolase enzyme reactions
First set of nonoxidative phase reactions
convert 6 ribulose-5P to 4 fructose-P and GAP
Second set of nonoxidative phase reactions
convert 4 fructose-P and GAP to 5 glucose-6P to make substrate for the PPP
Summary of PPP
SIX glucose-6P (C36) are metabolized to regenerate FIVE glucose-6P (C30)
where do the other 6 Carbons go??? (on another card)
where do the other 6 Carbons go???
they are lost as CO2 (6 molecules)
Metabolic Flux through PPP shunted in 3 directions
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
Regulation of G6PD activity: High NADP+
activate glucose-6P dehydrogenase
PPP activated to get NADPH
Regulation of G6PD activity: High NADPH
inhibit glucose-6P dehydrogenase
activate glycolysis
glutathione
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)
what can increase reactive oxygen species (ROS) in cells
mitochondrial aerobic respiration
drugs
fava beans
usually, NADPH levels can maintain rations of GSH:GSSG at 500:1
Cancer Cells
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
G6P dehydrogenase deficiency in humans
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
How might this observation explain the high incidence of G6PD deficiency?
they may have a protective effect against malaria
Which observation provides the most direct evidence that G6DP deficiency protects against malaria
People with G6PD deficiency have less sever malaria symptoms after exposure to plasmodium
SEE SLIDE 19!!!!!!!!!!!!!!!
Would you need to have a deficiency in G6PD to benefit from fava beans as an anti-malarial agent?
if you take vicine and have deficiency, you will get really sick
you’d have to eat a TON
vicine
induces oxidative stress in cells similar to primaquine
found in fava beans
