Hmp pathway

Pentode phosphate pathway

1. HMP shunt pathway Dr. Kayeen Vadakkan

2. HMP pathway (Pentose phosphate pathway) Hexose monophosphate pathway or HMP shunt is also called pentose phosphate pathway or phosphogluconate pathway. This is an alternative pathway to glycolysis and TCA cycle for the oxidation of glucose. HMP shunt is unique in generating two important products—pentoses and NADPH— needed for the biosynthetic reactions and other functions. The pathway starts with glucose 6-phosphate. As such, no ATP is directly utilized or produced in HMP pathway. It is a unique multifunctional pathway, since there are several interconvertible substances produced which may proceed in different directions in the metabolic reactions. The sequence of reactions of HMP shunt is divided into two phases—oxidative and non-oxidative.

3. Oxidative phase of HMP shunt Oxidative phase Glucose 6-phosphate dehydrogenase (G6PD) is an NADP-dependent enzyme that converts glucose 6-phosphate to 6-phosphogluconolactone. It is then hydrolysed by the gluconolactone hydrolase to 6-phosphogluconate. The next reaction involving the synthesis of NADPH is catalysed by 6-phosphogluconate dehydrogenase to produce 3 keto 6-phosphogluconate which then undergoes decarboxylation to give ribulose 5-phosphate.

4. Non-oxidative phase Non-oxidative phase The non-oxidative reactions are concerned with the interconversion of three, four, five and seven carbon monosaccharides. Ribulose 5-phosphate is acted upon by an epimerase to produce xylulose 5-phosphate while ribose 5-phosphate ketoisomerase converts ribulose 5-phosphate to ribose 5-phosphate. The enzyme transketolase catalyses the transfer of two carbon moiety from xylulose 5-phosphate to ribose 5-phosphate to give a 3-carbon glyceraldehyde 3-phosphate and a 7-carbon sedoheptulose 7-phosphate. Transaldolase brings about the transfer of a 3-carbon fragment (active dihydroxyacetone) from sedoheptulose 7-phosphate to glyceraldehyde 3-phosphate to give fructose 6-phosphate and four carbon erythrose 4-phosphate. Transketolase acts on xylulose 5-phosphate and transfers a 2-carbon fragment (glyceraldehyde) from it to erythrose 4-phosphate to generate fructose 6-phosphate and glyceraldehyde 3-phosphate. Fructose 6-phosphate and glyceraldehyde 3-phosphate can be further catabolized through glycolysis and citric acid cycle. Glucose may also be synthesized from these two compounds.

5. Uronic acid pathway This is an alternative oxidative pathway for glucose and is also known as glucuronic acid pathway. It is concerned with the synthesis of glucuronic acid, pentoses and vitamin, ascorbic acid. The reactions of Uronic acid pathway can be studied under four phases 1. Formation of UDP-glucuronate Glucose 6-phosphate is first converted to glucose 1-phosphate. UDP-glucose is then synthesized by the enzyme UDP-glucose pyrophosphorylase . UDP-glucose dehydrogenase oxidizes UDP-glucose to UDP-glucuronate. 2. Conversion of UDP-glucuronate to L- gulonate UDP-glucuronate loses its UDP moiety in a hydrolytic reaction and releases D-glucuronate which is reduced to L- gulonate by an NADPH-dependent reaction. 3. Synthesis of ascorbic acid L- Gulonate is the precursor for the synthesis of ascorbic acid (vitamin C) in many animals. The enzyme L- gulonolactone oxidase converts gulonate to ascorbic acid 4. Oxidation of L- gulonate L- Gulonate is oxidized to 3-ketogulonate and then decarboxylated to a pentose, L-xylulose. L-Xylulose is converted to D-xylulose via xylitol by a reduction (NADPH-dependent) followed by an oxidation (NAD+-dependent) reaction.