Other names for HMP shunt

OXIDATIVE PATHWAY HEXOSE MONOPHOSPHATE PATHWAY PHPSPHO-GLUCONATE PATHWAY PENTOSE PHOSPHATE PATHWAY

o Active in liver, adipose tissue, adrenal cortex, thyroid, erythrocytes, testes, and
lactating mammary gland

o Not active in non-lactating mammary gland o Low activity in skeletal muscle. muscle

L/OBJECTIVES

a. b. c.

Importance The reactions Clinical aspects

o The pentose phosphate pathway is an alternate route for the oxidation of

glucose.

Uses of PPP

To make pentoses for RNA, DNA, ATP, NADH, FADH To make NADPH needed for reductive biosynthesis (as needed in fatty acid
synthesis, cholesterol or steroid hormone synthesis)

To counter the effect of free radicals

Pathways requiring NADPH Synthesis

Fatty acid biosynthesis cholesterol biosynthesis neurotransmitter biosynthesis Nucleotide biosynthesis

Detoxifications

Reduction of oxidized glutathione Cytochrome P450 monoxygenases

Clinical importance

Genetic deficiency of glucose 6-phosphate dehydrogenase, is a major cause

of hemolysis of red blood cells, resulting in hemolytic anemia and affecting approximately 100 million people worldwide.

All REACTIONS OF THE PENTOSE PHOSPHATE PATHWAY OCCUR

IN THE CYTOSOL

HMPS OCCURS IN TWO PHASES

Phase I

Phase II

Oxidative Non-oxidative non-reversible reversible Generates NADPH Generates Ribose NADPH is generated when catalyzes the interconversion of glucose 6-phosphate is 3, 4, 5, 6, & 7 C sugars in a oxidized to ribose 5-phosphate series of Nox/rxns that can result in the synthesis of 5 C sugars for NA biosynthesis or the conversion of excess 5 C sugars into intermediates of the glycolytic pathway glucose 6-phosphate undergoes dehydrogenation and decarboxylation to yield ribulose 5-phosphate. ribulose 5-P is converted back to g-6-p by a series of reactions involving mainly two enzymes: transketolase and transaldolase

NADH and NADPH are NOT interchangeable NAD+ participates in synthesis of ATP NADPH is a reducing agent

Transketolase
Transfers the two-carbon unit (C 1 and 2 of a ketose) onto the aldehyde carbon

of an aldose sugar. It therefore effects the conversion of a ketose sugar into an aldose with two carbons less Simultaneously converts an aldose sugar into a ketose with two carbons more.

Transaldolase
Transfers the three-carbon unit (C 1, 2 and 3 of a ketose) onto the aldehyde

carbon of an aldose sugar. It therefore effects the conversion of a ketose sugar into an aldose with three carbons less Simultaneously converts an aldose sugar into a ketose with two carbons more.

Transketolase & Transaldolase catalyze transfer of 2-C or 3-C molecular fragments respectively, in each case from a ketose donor to an aldose acceptor.

Comparison with glycolysis

Oxidation utilizes NADP rather than NAD, CO2 is not produced in glycolysis No ATP is generated whereas ATP is a major product of glycolysis.

regulation
Primarily, the regulation of the pathway is through the supply and demand of

NADPH.

CLINICAL ASPECTS

G6PD deficiency leads to hemolytic anemia NADPH deficiency leads to cell damage (glutathione remains oxidized) Glucose-6-phosphate dehydrogenase deficiency causes hemolytic anemia Most G6PD-deficient individuals are asymptomatic

 Only in combination with certain environmental factors (sulfa antibiotics,

herbicides, antimalarials, *divicine) do clinical manifestations occur. *toxic ingredient of fava beans