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Pentose phosphate shunt (PPS) = Hexose monophosphate pathway (HMP)

Key functions:

Meet the needs of reducing equivalents for fatty acid synthesis

Generate ribose 5-phosphate for nucleotide and nucleic acid

synthesis

Involved in the P450 detoxification system

Summary reactions

6 G6-P +12 NADPH+ 6 Ribulose 5-phosphate + 6CO2 + 12 NADPH

6 Ribulose 5-phosphate 5 G 6-P + Pi

Net reaction G6-P 6CO2 + Pi [plus 12 NADPH]

Ann Rev Nutr27:179-192, 2007

INSULIN

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The hexose monophosphate pathway (pentose phosphate shunt).

competitive

inhibitor

FFA (-)

(-) (-)

2C= 2 carbons are transferred in transketolase rx.

3C=3 carbons are transferred in the transaldolase rx.

PNAS100:5578-80, 2003

Xylulose-5 phosphate

of the Hexose

Monophosphate

Pathway

PP2A = protein phosphatase 2A

ChREBP = carbohydrate-responsiveelement-binding protein

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themedicalbiochemistrypage.org/lipid-synthesi...

Malonyl CoA

An alternate source of reducing equivalents

(NADP-dependent

malate dehydrogenase)

Formation of ribose 5-phosphate from intermediates of glycolysis

http://themedicalbiochemistrypage.org/lipid-synthesis.htmlhttp://themedicalbiochemistrypage.org/lipid-synthesis.html

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NADPH versus NADH

In hepatic cytosol:

NADP+/NADPH ratio is 1:10 (favors the use of NADPH in

reductive biosynthesis)

NAD+/NADH ratio is 1000:1 (favors an oxidative role for NAD+)

Hence, NADPH is used as a source of electron for fatty acid and steroid biosynthesis

Other roles of NADPH

P-450 mono-oxygenase system

is important for detoxifying drugs

and foreign compounds,

converting them to more soluble

forms for urinary excretion.

Cytochrome P450 monooxygenase

cycle. Electrons move from NADPH

to FAD to FMN and then to the heme

iron.

Phagocytosis and the oxygen-

dependent pathway of microbial

killing.

cytotoxic

Neutrophils & monocytes

have O2-dependent and O2-

independent mechanisms

for killing bacteria.

The former involves the

NADPH oxidase(respiratory burst) and

myeloperoxidase (MPO)

s stem.

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A. Glutathione (G-SH).

B. Glutathione-mediated reduction of hydrogen

peroxide byNADPH.

Synthesis and some of the actions of nitric oxide.

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Pathways of glucose 6-phosphate metabolism in the erythrocyte.

Inherited (x-linked) disease G 6-P dehydrogenase deficiency is

characterized by hemolytic anemia caused by inability to detoxify

oxidizing agents. Therefore increase oxidative stress.

Low NADPH led to low glutathione pool, SH-group proteins denatureeasier forming insoluble compound (e.g. Heinz bodies) which may cross

link with other proteins and damage cell membrane.

RBC most affected.