Download Pentose phosphate pathway = PPP Pentose phosphate cycle

Pentose phosphate pathway = PPP
5 C containing phosphorylated sugar is produced
Pentose phosphate cycle
5 C containing phosphorylated sugar is produced
the pathway can work as a cycle
Glucose direct oxidation
alternative route for glucose oxidation besides glycolysis
in cytoplasm
Hexose monophosphate shunt
alternative metabolism for a 6 C containing sugar
Pentose phosphate pathway has two phases/branches:
1.) oxidative, irreversible, non-equilibrium, regulated, anaerob,
2.) nonoxidative, reversible, near-equilibrium, non-regulated, anaerob,
Characteristics of PPP:
each intermediate bears one phosphate at the terminal position
intermediates are 3-7 C-atom containing sugars and
6 C-atom cont. sugaracid: aldonic acid
Significance of PPP
1.) NADPH production in the oxidative phase for reductive synthetic reactions,
for biotransformation
2.) ribose-5-phosphate is produced after the oxidative branch in the nonoxidative branch
or if only the nonoxidative branch works from the end
for nucleotide synthesis
Oxidative, irreversible, regulated phase of PPP
The whole pathway is in the
cytoplasm.
reversible steps
in 3 steps
Comparison of transketolase and transaldolase
transketolase
transaldolase
thiamin pyrophosphate prosthetic group
no coenzyme
2 carbon cantaining keto group is
transfered from ketose to aldose
3 C containing keto group is transfered
from ketose to aldose
carbanions are resonance stabilized
If oxidative branch is absent e.g. muscle or
if NADPH requirement << ribose-5P need
gluconeogenesis
glycolysis
nonoxid. PPP
If NADPH and ribose-5P need are
balanced e.g. in liver
oxidative PPP
whole PPP
If only NADPH is necessary
e.g. in adipose t.
whole PPP
glycolysis
If NADPH and ATP needs e.g. in liver
Localization of PPP oxidative branch = where NADPH is necessary
1.) The whole pathway is found in the cytoplasm where lipid synthesis or
biotransformation is significant
¾FA synthesis: liver, adipose tissue, lactating mammary gland, brain
¾cholesterol synthesis: liver, skin, gut, brain
¾bile acid synthesis: liver
¾steroid hormon synth.: adrenal cortex, ovary, testis, adipocytes, brain
¾biotransformation: liver, lung, kidney, gut, blood cells
Regulation of pentose phosphate pathway oxidative phase and the whole pathway
1.) NADPH, the coenzyme product of the dehydrogenases inhibits the dehydrogenases,
no need for the PPP, if NADPH is not consumed in other reactions
2.) NADP, the substrate coenzyme activates the dehydrogenases, it is produced
by other reactions
3.) insulin in well fed state induces the PPP dehydrogenases to have NADPH for the
fatty acid (and further TAG) synthesis in adipocytes
4.) some molecules that induce reactions of biotransformation, induce PPP
dehydrogenase enzymes as well, to produce NADPH for biotransformation
Localization, speed and significance of nonoxidative branch of PPP
The nonoxidative reversible pathway is found in every cells having nucleus,
it goes from the end backword to produce ribose-5P for nucleotide/nucleic
acid synthesis (ribose-5P concentration of blood is low, even its absorption is negligable,
but possible across GLUT)
Nonoxidative reversible reactions take place to that direction and speed, that is
determined by the substrate/product ratio, overall the building of ribose-5P
to nucleotides. From fructose-6P and glyceraldehyde-3P the ribose-5P is
produced, from the end in the reverse direction e.g. in muscle.
The role of nucleotides:
ATP, GTP, CTP, UTP are energy donating compound in coupled reaction,
they have regulatory role in enzyme reaction, transporters
cAMP, cGMP are second messengers during signal transduction of neurotransmitters,
hormons, paracrin hormons
nucleic acids: RNA, DNA are synthesized from them
for the synthesis of nucleotide type coenzymes: NAD, NADP, FAD, FMN, SAM, CoA
Importance of PPP in red blood cells
glu-6P or
6P-gluconate
NADP
2 GSH
H2O2
GSSG
2 H2O
O2
dehydrogenases
NADPH
pentosephosphate path.
glutathione reductase glutathione peroxidase
H2O2 reacts with iron ion to form reactive oxygen species = ROS, that react with
unsaturated fatty acids in phospholipid membranes. This is the lipid peroxidation.
Fatty acids are broken, membrane becomes leaky, red blood cells are hemolysed.
If in the patient the glucose-6-P-dehydrogenase activity is decreased because of
mutation and the patient takes medicines (acetyl-salycilate, primaquin, sulfonamides,
etc.) that react with GSH, so GSH is not enough for reduction of hydrogen-peroxide,
rbc. are hemolyzed.
Before uroic acid pathway:
glucose from blood
↓hexokinases
glu-6P
phosphoglucomutase
epimerase
UDP-gal
glu-1P
gal-1P-uridyl transferase
UDP-glu
gal-1P
galactokinase
gal from blood (from lactose e.g.)
stored glycogen
↓
glu-1P
UTP
glu-1P uridyltransferase
PP
UDP-glu
Uronic acid pathway
UDP-glucuronate is needed
for conjugation reactions
in biotransformation and
synthesis of heteropolysaccharides
branchpoint
to ascorbate
synthesis:
not in humans
continuation of PPP:
vitamin: not produced in humans
: interconnection in carbohydrate metabolism
glycolysis
gluconeogenesis
fructose degradation
pentosephosphate path.
glycogen metabolism
lactose/galactose met.
uronic acid pathway
aminosugar synth.
glycoprotein synth.
proteoglycan synt.