Ferchmin 2017
Part of glucose was not metabolized through glycolysis but through “a shunt” involving
phosphor-pentoses
1) Pentose phosphate pathway or shunt (PPP).
2) Oxidative and isomerization parts.
3) Regulation
4) Metabolic roles of PPP
5) Reduction of glutathione.
In glycolysis there was no net
oxidation/reduction only
“reshuffling” of the redox state
of the carbons
PENTOSE PHOSPHATE SHUNT or
HEXOSE MONOPHOSPHATE PATHWAY
This pathway consists of two parts:
1) Glucose-6-P undergoes two oxidations by NADP+, the second is
an oxidative decarboxylation that forms a pentose-P.
2) The P-pentoses that are formed during the first part are
transformed into glucose-6-P.
1
The phosphoryl group on the 2′-hydroxyl group of one of the ribose
units of NADPH distinguishes NADPH from NADH.
There is a fundamental distinction between NADPH and NADH in
biochemistry: NADH is oxidized by the respiratory chain to generate ATP,
whereas NADPH serves as a reductant in biosynthetic processes.
2
GPDH deficiency is relatively common
in persons with roots from regions
with endemic malaria.
In glycolysis followed by TCA (Kreb’s) cycle the first
3 Cs
to be converted to CO2 are # 3 and 4. In PPP is C #1.
2) Nonoxidative steps of pentose phosphate shunt
transketolase
requires thiamine
pyrophosphate
(vitamin B1)
Positive
regulator of
lipid
synthesis
transketolase
requires thiamine
pyrophosphate
(vitamin B1)
4
Melvin Calvin using 14C elucidated the dark reactions of photosynthesis which are
the reverse reactions of the pentose shunt.
5
GSSG is oxidized
and GSH reduced
glutathione which
will be discussed
in next page
6
7
The pentose phosphate pathway (PPP) was explained in the previous
slides. The next three slides address the anti-oxidative role of the PPP
Glutathione synthesis is not ribosomal and glutathione is not directly encoded in DNA.
Notice the unusual bonds between cysteine and glutamate.
Unusual “peptide” bond.
8
Conceptual link between the NADPH+H+ dehydrogenases and glutathione
reductase. The sketch below is not a real metabolic pathway just an illustration.
9
Proposed mechanism of glutathione peroxidase
Glutathione peroxidase has selenocysteine a rare amino acid that contains selenium. The story
of selenocysteine incorporation into proteins is unusual and exciting.
There are many antioxidants that neutralize the oxygen reactive species (ROS). Among them
are: vitamins C and E and recently the tomato red pigment, lycopene. Lycopene, became
10
notorious for reportedly preventing prostate cancer and retinal macular degeneration.