Overview
- Function
- Pathway
- occurs in cytoplasm of all cells
- no ATP consumed or generated
- 2 phases
- oxidative
- produces NADPH
- glucose 6-phosphate (G6P) → 6-phosphogluconate
- catalyzed by glucose 6-phosphate dehydrogenase (G6PDH)
- rate limiting step
- activated by NADP+, insulin
- inhibited by NADPH
- catalyzed by glucose 6-phosphate dehydrogenase (G6PDH)
- irreversible
- nonoxidative
- oxidative
- Clinical relevance
- glucose-6-phosphate dehydrogenase (G6PDH) deficiency
- pathophysiology
- ↓ NADPH production
- cells (specifically RBCs) lose protection against oxidizing agents
- cannot regenerate glutathione
- cells (specifically RBCs) lose protection against oxidizing agents
- XR
- most common human enzyme deficiency
- ↑ prevalence among blacks
- ↑ malarial resistance
- by shortening the circulation life of RBCs
- Plasmodium does not have enough time for life span
- plasmodium does not have defense against free radicals
- ↑ in free radicals kills parasite
- by shortening the circulation life of RBCs
- ↑ malarial resistance
- ↓ NADPH production
- presentation
- episodic hemolytic anemia
- intravascular hemolysis
- normocytic
- 2-3 days post precipitating stress
- foods
- fava beans
- common in Mediterranean foods
- presentation
- pallor, hemoglobinuria 24-48 post ingestion
- fava beans
- drugs
- sulfonamides, primaquine, antituberculosis drugs
- infection
- free radicals generated by the immune system
- foods
- Heinz bodies
- oxidized hemoglobin that precipitates within RBCs
- bite cells
- back pain
- episodic hemolytic anemia
- test
- active hemolysis screen
- pathophysiology
- glucose-6-phosphate dehydrogenase (G6PDH) deficiency
- Heinz body prep
Introduction
The HMP shunt, also known as the pentose phosphate pathway, is a metabolic pathway that occurs in the cytoplasm of cells in most organisms. It is a parallel pathway to glycolysis, and its primary function is to generate NADPH and ribose-5-phosphate, which are important for various cellular processes, including biosynthesis and antioxidant defense.
The HMP shunt consists of two phases: the oxidative phase and the non-oxidative phase. In the oxidative phase, glucose-6-phosphate is oxidized and decarboxylated to generate NADPH and ribulose-5-phosphate. This phase also produces intermediate metabolites that can enter glycolysis or be used for biosynthesis. In the non-oxidative phase, the intermediates of the oxidative phase are rearranged and converted to other sugars, including ribose-5-phosphate, which is an important component of nucleotides and nucleic acids.
Types
There are two types of HMP shunt, which are the oxidative phase and the non-oxidative phase.
- Oxidative phase: In this phase, glucose-6-phosphate is oxidized and decarboxylated to generate NADPH and ribulose-5-phosphate. This phase consists of three enzyme-catalyzed reactions, which are:
- Glucose-6-phosphate dehydrogenase (G6PD) catalyzes the conversion of glucose-6-phosphate to 6-phosphogluconolactone, generating NADPH in the process.
- 6-Phosphogluconolactonase catalyzes the hydrolysis of 6-phosphogluconolactone to 6-phosphogluconate.
- 6-Phosphogluconate dehydrogenase catalyzes the conversion of 6-phosphogluconate to ribulose-5-phosphate, generating another molecule of NADPH in the process.
- Non-oxidative phase: In this phase, the intermediates of the oxidative phase are rearranged and converted to other sugars, including ribose-5-phosphate, which is an important component of nucleotides and nucleic acids. This phase involves a series of enzyme-catalyzed reactions that convert ribulose-5-phosphate to a variety of sugars, including glucose-6-phosphate and fructose-6-phosphate, which can enter glycolysis. The non-oxidative phase is also important for generating pentose sugars, which are used in the synthesis of nucleotides, nucleic acids, and coenzymes.
Both the oxidative and non-oxidative phases of the Hexose Monophosphate shunt are important for providing the cell with NADPH, which is needed for various biosynthetic pathways, as well as for maintaining the cell’s redox balance.
Features of the HMP Shunt
The HMP (hexose monophosphate) shunt, also known as the pentose phosphate pathway, has several important features, including:
- Generation of NADPH: One of the primary functions of the Hexose Monophosphate shunt is to generate NADPH, which is an important cofactor for various biosynthetic reactions, including fatty acid and steroid synthesis. NADPH is also important for the maintenance of the cell’s redox balance and antioxidant defense.
- Generation of ribose-5-phosphate: The HMP shunt also generates ribose-5-phosphate, which is an important component of nucleotides and nucleic acids. Ribose-5-phosphate can be synthesized from intermediates of the HMP shunt, such as ribulose-5-phosphate and xylulose-5-phosphate.
- An alternative pathway for glucose metabolism: The HMP shunt is an alternative pathway for glucose metabolism, which can occur in parallel with glycolysis. While glycolysis generates ATP and pyruvate, the HMP shunt generates NADPH and ribose-5-phosphate.
- Regulation by cellular needs: The HMP shunt is regulated by the needs of the cell. For example, when the cell needs more NADPH for biosynthetic reactions, the HMP shunt is upregulated, while when the cell needs more ATP, glycolysis is upregulated.
- Role in antioxidant defense: NADPH generated by the HMP shunt is used in the synthesis of glutathione, which is an important antioxidant that protects cells from oxidative damage. The HMP shunt is therefore important for maintaining the cell’s antioxidant defense.
- Dysregulation in disease: Dysregulation of the HMP shunt has been implicated in a variety of diseases, including cancer, metabolic disorders, and neurodegenerative diseases. For example, increased activity of the HMP shunt has been observed in some cancer cells, which may contribute to their increased proliferation and survival.
Studies
There have been numerous studies on the HMP (hexose monophosphate) shunt, also known as the pentose phosphate pathway, which have contributed significantly to our understanding of its role in cellular metabolism and disease. Here are some examples of studies on the Hexose Monophosphate shunt:
- Regulation of the HMP shunt: Several studies have investigated the regulation of the HMP shunt, including the roles of enzymes and metabolic intermediates in its activation and inhibition. For example, studies have shown that glucose-6-phosphate dehydrogenase (G6PD) is a key regulatory enzyme in the HMP shunt, and its activity is regulated by factors such as NADP+ and oxidative stress.
- HMP shunt and cancer: Several studies have investigated the role of the HMP shunt in cancer metabolism. For example, some cancer cells have been shown to exhibit increased HMP shunt activity, which allows them to generate NADPH and biosynthetic intermediates required for rapid proliferation.
- HMP shunt and oxidative stress: Studies have investigated the role of the Hexose Monophosphate shunt in protecting cells from oxidative stress. NADPH produced by the HMP shunt is used in the regeneration of glutathione, a key antioxidant molecule that protects cells from oxidative damage.
- HMP shunt and metabolic disorders: Studies have investigated the role of the Hexose Monophosphate shunt in metabolic disorders such as diabetes and obesity. For example, it has been shown that dysregulation of the HMP shunt in pancreatic beta cells can contribute to the development of diabetes.
- Hexose Monophosphate shunt and neurodegenerative diseases: Studies have investigated the role of the HMP shunt in neurodegenerative diseases such as Alzheimer’s and Parkinson’s. For example, it has been shown that dysregulation of the HMP shunt can contribute to the accumulation of toxic metabolites in the brain and neuroinflammation.
Check out Ultimate USMLE Step 1 Study Notes.