2.0 NADHP

nicotinamide adenine dinucleotide phosphate NADPH

represents an important electron donator that is used in a variety of biological settings

NADPH is formed through the pentose phosphate pathway PPP

an anabolic pathway that runs to parallel to upper glycolysis

that involves the oxidation of glucose

PPP AKA hexose moniphosphate shunt

it occurs virtually in all cells and tissue in the body

PPP primary outputs

• NADPH- used in reductive biosynthesis in cells → fatty acid

  • formed in the oxidative phase

• ribose 5 phosphate,→ nucleotides

• erythrose 4 phosphate → aromatic amino acids

NADPH is generated in the oxidative (irriversible) phase of the PPP

• 2 molecules of NADP+ are reduced → NADPH

• using the energy stored on G6P

• regulated by the enzyme glucose 7 phosphate dehydrogenase G6PD

the initial oxidation of G6P →6 phosphogluconate is catalysed by G6PD and is irreversible

this is the rate limiting step if the PPP

the ratio of H to + is the main controling factor of the reaction rate

when H lvls are low → G6PD is activated

G6PD pathway is very efficient:

maintains the ratio of H/+ at -100 in the liver of a normal healthy individual

under conditions where both H + pentose phosphate are needed

the pathway may terminate after the oxidative phase

H acts as a reducing agent in biochemical processes

and acts as a co factor in multiple anabolic reactions

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NADPH is mainly used for

• fatty acid synthesis,

• reducing the effect of oxidative stress, liver + RBC

• CYP450 enzymes-

• WBC need H to create superoxide radicals to cause oxidative damage to phagocytosed microbes

• glands

50% fatty acid synthesis

all cells rely on H reducing power  to produce cholesterol + fatty acids + phospholipids

CYP450 enzymes

the liver needs H to neutralise toxins + hormones using cytochrome P450 pathways

WBC

need H to create superoxide radicals to cause oxidative damage to phagocytosed microbes

Glands

use H to make steroid hormones

PPP activity is minimal in muscles and brain

where almost all of the glucose is used glycolysis for ATP production

PPP activity accounts for a significant portion of the total glucose oxidation in tissues

with active fatty acid + cholesterol synthesis including the liver

around 30% of glucose present in the liver

ends up being metabolised by PPP