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HMP Shunt Pathway with Structures

    In this HMP shunt pathway with structures post we have briefly explained about Reactions of oxidative phase, Non-oxidative phase, Significance, of Hexose Monophosphate Shunt pathway.

    Hexose Monophosphate Shunt pathway is also known as the pentose phosphate pathway or the phosphogluconate pathway. For the oxidation of glucose, this is an alternative to glycolysis and the TCA cycle. Hexose Monophosphate Shunt pathway on the other hand, is more anabolic in character since it is involved in the production of NADPH and pentoses.

    Hexose Monophosphate Shunt Pathway

    This pathway starts with glucose-6-phosphate as a key metabolite. Since, this pathway comprises both pentoses and hexoses, it is also referred to as the pentose phosphate pathway.

    This pathway consists of two phases namely the oxidative phase and the regenerative phase (non oxidative phase). The oxidative phase, in which glucose-6-phosphate is oxidized and decarboxylated to give ribulose-5-phosphate. In this phase two NADPH (NADH equivalent) is formed.

    The fundamental difference between NADPH and NADH is that NADH is oxidised by the respiratory chain to generate ATP whereas NADPH serves as a hydrogen and electron donor in reductive biosynthesis of molecule such as fatty acids and cholesterol.

    In cells that are not using ribose-5-phosphate for biosynthesis, the nonoxidative phase recycles six molecules of the pentose into five molecules of the hexose, glucose-6-phosphate, allowing continued production of NADPH and converting glucose-6- phosphate (in six cycles) to CO2 .

    Location

    The enzymes of Hexose Monophosphate Shunt pathway are located in the cytosol. The tissues such as liver, adipose tissue, adrenal gland, erythrocytes, testes and lactating mammary gland, are highly active in Hexose Monophosphate Shunt pathway. Most of these tissues are involved in the biosynthesis of fatty acids and steroids which are dependent on the supply of NADPH.

    HMP Shunt Pathway with Structures

    Oxidative Phase

    Step 1

    In the first step, glucose-6-phosphate dehydrogenase oxidizes glucose-6-phosphate to 6-phosphoglucono-δ-lactone and reduces one molecule of NADP+ to NADPH.

    Step 2

    In the second step, gluconolactonase cleaves the internal ester bond, which gives 6-phosphogluconate.

    Step 3

    In the third step, 6-Phosphogluconate dehydrogenase reduces another molecule of NADP+ and decarboxylates 6-phosphogluconate to the pentose, ribulose-5-phosphate.

    HMP shunt Pathway

    HMP Shunt Pathway with Structures; Oxidative Phase

    Non-oxidative Phase

    The non-oxidative phase involves the enzymes ribulose-5-phosphate epimerase (RE), ribulose-5-phosphate isomerase (RI), transketolase (TK), and transaldolase (TA).

    Step 1

    Two molecules of ribulose-5-phosphate are converted to xylulose-5-phosphate by ribulose-5-phosphate epimerase, and a third one is converted to ribose-5-phosphate by ribulose-5-phosphate isomerase.

    Step 2

    Transketolase transfers a C2 unit from one xylulose-5-phosphate to the ribose-5- phosphate, yielding glyceraldehyde-3-phosphate and the C7 sugar sedoheptulose-7- phosphate.

    Step 3

    Transaldolase transfers a C3 unit from sedoheptulose-7-phosphate back to glyceraldehyde-3-phosphate, which yields fructose-6-phosphate and the C4 sugar erythrose-4-phosphate.

    Step 4

    Transketolase transfers a C2 unit from the second molecule of xylulose-5-phosphate to erythrose-4-phosphate. This yields a second molecule of fructose-6-phosphate and again glyceraldehyde-3-phosphate.

    HMP shunt Pathway

    Hexose Monophosphate Shunt pathway: Non-oxidative phase

    Significance

    Hexose Monophosphate Shunt pathway is unique in generating two important products-pentoses and NADPH needed for the biosynthetic reactions and other functions.

    Pentoses

    In the Hexose Monophosphate Shunt pathway, hexoses are converted into pentoses, the most important being ribose 5-phosphate. This pentose or its derivatives are useful for the synthesis of nucleic acids (RNA and DNA) and many nucleotides such as ATP, NAD+, FAD and CoA.

    Skeletal muscle is capable of synthesizing pentoses, although only the first few enzymes of Hexose Monophosphate Shunt pathway are active. lt, therefore, appears that the complete pathway of Hexose Monophosphate Shunt pathway may not be required for the synthesis of pentoses.

    NADPH

    NADPH is required for the reductive biosynthesis of fatty acids and steroids hence Hexose Monophosphate Shunt pathway is more active in the tissues concerned with lipogenesis, e.g. adipose tissue, liver etc.

    NADPH is used in the synthesis of certain amino acids involving the enzyme glutamate dehydrogenase.

    There is a continuous production of H2O2 in the living cells which can chemically damage unsaturated lipids, proteins and DNA. This is, however, prevented to a large extent through antioxidant reactions involving NADPH. Glutathione mediated reduction of H2O2 is given in the next column Glutathione (reduced, GSH) detoxifies H2O2, peroxidase catalyses this reaction. NADPH is responsible for the regeneration of reduced glutathione from the oxidized one.

    Microsomal cytochrome P450 system (in liver) brings about the detoxification of drugs and foreign compounds by hydroxylation reactions involving NADPH.

    Phagocytosis is the engulfment of foreign particles, including microorganisms, carried out by white blood cells. The process requires the supply of NADPH.

    Special functions of NADPH in RBC: NADPH produced in erythrocytes has special functions to Perform. lt maintains the concentration of reduced glutathione which is essentially required to preserve the integrity of RBC membrane. NADPH is also necessary to keep the ferrous iron (Fe2+) of hemoglobin in the reduced state so that accumulation of methemoglobin (Fe3+) is prevented.

    Further Readings

    Reference