HMP Shunt

The sources of NADPH for synthesis of fatty acids are the pentose phosphate pathway

No ATP is directly consumed or produced in the hexose monophosphate shunt (HMP).

Ref: Harper’s Textbook of Biochemistry, 27th Edition, Pages 177, 189; Lippincott’s Biochemistry, 5th Edition, Pages 104, 113, 145, 192

The oxidative phase generates NADPH and the non oxidative phase generates pyruvate. The oxidative phase generated NADPH, however the Non oxidative phase generates Ribose precursors that are required for nucleic acid biosynthesis.

Ref: Lippincott’s Biochemistry 3rd Edition, Page 144, 153; Text Book of Biochemistry By Dr. G. R. Agarwal, Dr. O. P. Agarwal, Dr. (Mrs) Kiran Agarwal, Page 133.

NADPH is used by glutathione reductase to maintain glutathione in the reduced form. Pentose phosphates are not needed in the red blood cell. The pentose phosphate pathway is not a source of NADH & ATP is not generated from NADPH.

Although glucose 6-phosphate is common to both pathways, the pentose phosphate pathway is markedly different from glycolysis. 

• Oxidation utilizes NADP rather than NAD, 
• CO2, which is not produced in glycolysis, is a characteristic product 
• No ATP is generated in the pentose phosphate pathway, whereas it is a major product of glycolysis.

Ref: Harper 28th edition, chapter 21.

The two major pathways of catabolism of glucose, glycolysis and the pentose phosphate pathway, having several common metabolites (as for example, glucose 6-phosphate and glyceraldehyde 3-phosphate) markedly differ in many other features.CO2 is produced in the pentose phosphate pathway but not in glycolysis; Mg2+ ions are required for both glycolysis (for the phosphorylation of glucose by glucokinase) and the pentose phosphate pathway (for the functioning of transketolase and several other enzymes). Thiamine is used only in the pentose phosphate pathway (in the form of thiamine pyrophosphate as the coenzyme of transketolase). Thiamine-dependent enzymes are not involved in glycolysis taking part on later stages when pyruvate is either converted to acetyl CoA by pyruvate dehydrogenase or (in microorganisms) is reduced to ethanol by pyruvate decarboxylase.

The co enzyme used for the de novo fatty acid synthesis is NADPH. The hexose monophosphate pathway provides a major portion of cell’s NADPH for fatty acid synthesis. Tissues having active lipogenesis such as liver, adipose tissue and lactating mammary gland have an active HMP shunt pathway also. 

• The formation of NADPH for synthesis of fatty acids and steroids, and maintaining reduced glutathione for antioxidant activity.
• The synthesis of ribose for nucleotide and nucleic acid formation. 

Ans:B .) Enzymes of TCA cycle

Erythrocytes (RBC) lack mitochondria (so TCA cycle enzymes) and completely rely on glucose as their metabolic fuel. They metabolize it by anaerobic glycolysis.

A i.e. Glycerol -3-phosphate

D i.e. NADPH

Ans:C : G-6-P- dehydrogenase.

The Hexose MonoPhosphate Shunt

It is also known as “Pentose phosphate Pathway” (PPP). This is alternative Glucose oxidation pathway.
• Location: Cytoplasm of cells of the liver, adrenal cortex, and lactating mammary glands.
• Substrate: Glucose-6-phosphate.
• Oxidative portion: Irreversible.
Generates two NADPH, which can then be used in fatty acid synthesis and cholesterol synthesis and for maintaining reduced glutathione inside RBCs.
• Nonoxidative portion: Reversible.
Generates intermediate molecules (ribose-5-phosphate; glyceraldehyde-3-phosphate; fructose-6-phosphate) for nucleotide synthesis and glycolysis.
• Regulation: Key enzyme in the pentose-phosphate pathway is glucose-6-phosphate dehydrogenase. Levels of glucose-6-phosphate dehydrogenase are increased in the liver and adipose tissue when large amounts of
carbohydrates are consumed. Glucose-6-phosphate dehydrogenase is stimulated by NADP+ and inhibited by NADPH and by palmitoyl-CoA (part of the fatty acid synthesis pathway).
• Purpose: Functions as an alternative route for glucose oxidation that does not directly consume or produce ATP.

A i.e. Liver, B i.e. Testes  C i.e. Lactating mammary gland;

D i.e. The oxidative phase generates NADPH and non oxidative phase generates pyruvate

The oxidative (irreversible) phase of HMP shunt produce NADPH and ribulose 5 phosphateQ, whereas reversible non-oxidative phase catalyze the interconversion of 3, 4, 5, 6, and 7 carbon sugars, and permit ribulose 5 phosphate to be converted either to ribose 5 phosphate (needed for nucleotide synthesis) or to intermediates of glycolysis – fructose 6 – PO4 & glyceraldehyde 3­phosphateQ

D i.e. HMP pathway

Pentose phosphate pathway/Phosphogluconate pathway/Hexose monophosphate shunt

• It is a process that generates NADPH and pentoses (5-carbon sugars).
• There are two distinct phases in the pathway.

– The first is the oxidative phase, in which NADPH is generated, and the

– Second is the non-oxidative synthesis of 5-carbon sugars.

• This pathway is an alternative to glycolysis.
• While it does involve oxidation of glucose, its primary role is anabolic rather than catabolic.
• For most organisms, it takes place in the cytosol

NADPH is involved as donor of reducing equivalents in both the reduction of the 3-ketoacyl and of the 2, 3-unsaturated acyl derivatives.

The oxidative reactions of the pentose phosphate are the chief source of the hydrogen required for the reductive synthesis of fatty acids.

• HMP is an alternative route for the oxidation of glucose (beside glycolysis). It is also called as “pentose phosphate pathway”, “Dickens – Horecker pathway”, “Shunt pathway” or “phosphogluconate oxidative pathway”. 
• HMP shunt is required for provision of reduced NADPH and fiver-carbon sugars e.g. ribose (Pentose phosphates) for nucleic acid synthesis.
• Normally, 90% of glucose is oxidized by glycolysis and 10% is oxidized by HMP shunt. However, in liver and RBCs HMP shunt accounts for oxidation of 30% glucose.
• HMP shunt occurs in the cytosol. It is highly active in liver, adipose tissue, adrenal cortex, lens, cornea, lactating (but not the nonlactating) mammary gland, Gonads (testis, ovary) and erythrocytes. Activity of this pathway is minimal in muscle and brain, where almost all of the glucose is degraded by glycolysis.

Ans. is ‘c’ i.e., ATP is produced

HMP shunt does not produce ATP.

HMP shunt

HMP shunt is a multicyclic process in which 3 molecules of glucose-6-phosphate give rise to 3 molecules of CO₂ and 3 molecules of 5-carbon sugars (ribulose-5-phosphate). The latter are rearranged to generate 2 molecules of glucose-6-phosphate (through fructose-6-phosphate) and l molecule glyceraldehyde-3-phosphate. HMP shunt does not generate ATP.

3 Glucose-6-phosphate + 6 NADP →  2 glucose-6-phosphate + 1 glyceraldehyde-3-phosphate + 6 NADPH 3CO2

The reaction of HMP shunt are divided into two phases : –

i)  Phase I (Oxidative irreversible phase) : – During this phase, 3 molecules of glucose-6-phosphate are oxidized with generation of 6 molecules of NADPH, and three molecules of pentose phosphate (ribulose‑5-phosphate), with liberation of three molecules of CO₂. Metabolites produced during this phase are 6- phosphoglucanolactone, 6-phosphogluconate and ribulose-5-phosphate.

ii)  Phase II (Non-oxidative reversible phase) : – During this phase, pentose phosphate is converted to inter­mediates of glycolysis, i.e., glucose-6-phosphate and glyceraldehyde-3-phosphate. Intermediary metabolites of this phase are xylulose-5-phosphate, ribose-5-phosphate, sedoheptulose-7-phosphate, erythrose-4- phosphate and fructose-6-phosphate.

HMP shunt occurs in the cytosol. It is highly active in liver, adipose tissue, adrenal cortex, lens, cornea, lactating (but not the nonlactating) mammary gland, Gonads (testis, ovary) and erythrocytes. Activity of this pathway is minimal in muscle and brain, where almost all of the glucose is degraded by glycolysis.

Ans. is ‘a’ i.e., HMP shunt

Oxidized glutathione is reduced by the help of NADPH, which is generated by NADPH.