HMP Shunt and Pentose Phosphate Pathway Overview
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Questions and Answers

What is the primary aim of the pentose phosphate pathway?

  • To produce ribose 5-phosphate and NADPH (correct)
  • To generate ATP from glucose
  • To synthesize GTP and NADH
  • To break down glucose into pyruvate

Which of the following tissues primarily relies on NADPH for fatty acid biosynthesis?

  • Erythrocytes
  • Testes and ovaries
  • Liver and adipose tissue (correct)
  • Muscle

What is formed during the irreversible oxidative reactions of the pentose phosphate pathway?

  • FADH2 and ribose 5-phosphate
  • Glucose and ribose
  • Ribulose 5-phosphate, NADPH, and CO2 (correct)
  • NADH and glucose

Where does the pentose phosphate pathway primarily occur within the cell?

<p>Cytosol (D)</p> Signup and view all the answers

Which component is critical for detoxifying hydrogen peroxide in erythrocytes?

<p>NADPH (B)</p> Signup and view all the answers

What are the products of the irreversible reaction involving 6-phosphogluconolactone hydrolase?

<p>Ribulose 5-phosphate and NADPH (A)</p> Signup and view all the answers

Which coenzyme is required for the activity of transketolase?

<p>Thiamine pyrophosphate (TPP) (D)</p> Signup and view all the answers

What distinguishes ribulose from ribose?

<p>Ribulose is a ketone, while ribose is an aldehyde. (D)</p> Signup and view all the answers

What defines ribulose and xylulose as epimers?

<p>They differ in the placement of -OH group at C3. (D)</p> Signup and view all the answers

Which B vitamins are particularly emphasized in their role in metabolism, specifically carbohydrate metabolism?

<p>Thiamine and niacin (A)</p> Signup and view all the answers

What is the primary role of transketolase in carbohydrate metabolism?

<p>It transfers a 2 carbon unit from one sugar to another. (A)</p> Signup and view all the answers

Which of the following compounds is formed by the action of transaldolase?

<p>Fructose 6 P (B)</p> Signup and view all the answers

Which of the following statements correctly describes NADPH's function?

<p>NADPH serves as an electron donor in reductive biosynthesis. (C)</p> Signup and view all the answers

What are the products formed when transketolase transfers a 2 carbon unit from Xylulose 5 P to Ribose 5 P?

<p>Glyceraldehyde 3 P and Fructose 6 P (C)</p> Signup and view all the answers

What is the primary product produced by the oxidative portion of the pentose phosphate pathway?

<p>Ribulose 5-phosphate (C)</p> Signup and view all the answers

Which reactions result in the removal of 3 CO2 molecules in carbohydrate metabolism?

<p>The oxidative phase of the pentose phosphate pathway. (A)</p> Signup and view all the answers

Under which conditions is ribose 5-phosphate biosynthesis favored over NADPH production?

<p>When the need for ribose in nucleotides is greater (C)</p> Signup and view all the answers

Which enzyme catalyzes the irreversible oxidation of glucose 6-phosphate to produce NADPH?

<p>Glucose 6-phosphate dehydrogenase (D)</p> Signup and view all the answers

Which of the following reactions is categorized as a non-oxidative reaction in the pentose phosphate pathway?

<p>Conversion of glyceraldehyde 3-phosphate to ribose 5-phosphate (B)</p> Signup and view all the answers

What role does NADPH play in the pentose phosphate pathway?

<p>It is a potent competitive inhibitor of glucose 6-phosphate dehydrogenase. (B)</p> Signup and view all the answers

<h1>=</h1> <h1>=</h1> Signup and view all the answers

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Flashcards

Pentose Phosphate Pathway (PPP)

An alternative pathway for glucose oxidation that does not generate ATP or energy but produces essential molecules like NADPH and ribose-5-phosphate.

Oxidative Phase of the PPP

The first phase of the PPP, where glucose-6-phosphate is oxidized to produce NADPH and ribulose-5-phosphate. This phase is critical for reducing power (NADPH) and biosynthesis.

Non-Oxidative Phase of the PPP

The second phase of the PPP, where ribulose-5-phosphate is converted into ribose-5-phosphate and other intermediates, depending on the cell's needs for nucleotide biosynthesis.

NADPH

A vital coenzyme produced in the PPP, playing a role in reducing molecules like fatty acids, amino acids, and steroids. It also protects cells from oxidative stress.

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Ribose-5-phosphate

A 5-carbon sugar phosphate essential for nucleotide synthesis, DNA, RNA, and energy carriers like ATP and GTP.

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6-Phosphogluconate Dehydrogenase

An enzyme involved in the oxidative phase of the pentose phosphate pathway (PPP). It catalyzes the irreversible conversion of 6-phosphogluconate to 6-phosphogluconolactone, generating CO2 and NADPH.

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Ribulose 5-Phosphate

A pentose sugar phosphate, specifically an aldopentose, produced in the oxidative phase of the PPP. It plays a key role in nucleotide biosynthesis.

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Transketolase

An enzyme that transfers 2-carbon units in the non-oxidative phase of the PPP. It requires thiamine pyrophosphate (TPP) as a coenzyme.

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Transaldolase

An enzyme involved in the non-oxidative phase of the PPP. It transfers 3-carbon units.

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Thiamine Pyrophosphate (TPP)

A coenzyme involved in the PPP, particularly in the transketolase enzyme. It's derived from vitamin B1.

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What is the first step in the oxidative phase of the pentose phosphate pathway?

The irreversible oxidation of glucose 6-phosphate to 6-phosphogluconolactone, catalyzed by glucose 6-phosphate dehydrogenase (G6PD). This reaction produces NADPH and is the primary regulatory step in the pentose phosphate pathway.

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How is 6-phosphogluconolactone converted to 6-phosphogluconate?

The enzyme 6-phosphogluconolactone hydrolase catalyzes the hydrolysis of 6-phosphogluconolactone to produce 6-phosphogluconate.

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What is the enzyme involved in the oxidative decarboxylation of 6-phosphogluconate?

The oxidative decarboxylation of 6-phosphogluconate to ribulose 5-phosphate, which is catalyzed by 6-phosphogluconate dehydrogenase. This reaction produces NADPH and releases CO₂.

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What happens in the non-oxidative phase of the pentose phosphate pathway?

A series of non-oxidative reactions that convert ribulose 5-phosphate into various intermediates, including ribose 5-phosphate, glyceraldehyde 3-phosphate, and fructose 6-phosphate.

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How can the pentose phosphate pathway produce ribose 5-phosphate without the oxidative phase?

The pentose phosphate pathway can provide ribose 5-phosphate for nucleotide biosynthesis even when the oxidative phase is not active. This occurs through the non-oxidative phase, which converts intermediates like glyceraldehyde 3-phosphate and fructose 6-phosphate into ribose 5-phosphate.

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Transketolase Activity

The process of transferring two-carbon units between sugars in the non-oxidative phase of the pentose phosphate pathway. It requires a coenzyme, thiamine pyrophosphate (TPP).

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Transaldolase Activity

The enzyme involved in the non-oxidative phase of the pentose phosphate pathway that transfers three-carbon units from one sugar to another.

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Reduction reaction

The process of altering the structure of a molecule by removing oxygen atoms. In biological systems, this often involves a simultaneous addition of electrons and protons (hydrogen atoms).

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Study Notes

HMP Shunt Overview

  • The HMP shunt is an alternative pathway for glucose oxidation.
  • Its goal is not ATP or energy production.
  • It produces NADPH, acting as a biochemical reducing agent (hydrogen carrier). NADPH plays no role in energy production, as NADH and FADH2 are used in the electron transport chain (ETC).
  • It synthesizes ribose 5-phosphate, needed for nucleotide synthesis.

Pentose Phosphate Pathway (PPP)

  • The aim of the PPP is to form pentose sugar.
  • Also known as the hexose monophosphate shunt (HMP) shunt.
  • Begins with glucose 6-phosphate (G6P) converting it into ribose.
  • The first phase produces 6-phosphogluconate.

HMP Shunt Steps (Oxidative)

  • Three reactions lead to the formation of ribulose 5-phosphate, CO2, and two NADPH molecules per glucose 6-phosphate oxidized.
  • This part of the pathway is crucial in the liver, lactating mammary glands, adipose tissue, erythrocytes, testes, ovaries, placenta, and adrenal cortex. It is also vital in phagocytic cells.

HMP Shunt Steps (Non-Oxidative)

  • These reversible reactions convert sugars with 3 to 7 carbon atoms.
  • Ribulose 5-phosphate can be converted into ribose 5-phosphate (needed for nucleotide synthesis).
  • Or into intermediates of glycolysis (fructose 6-phosphate and glyceraldehyde 3-phosphate).

HMP Shunt Regulation

  • Cells involved in reductive biosynthesis (e.g., fatty acid, amino acid, steroid synthesis) need more NADPH than ribose 5-phosphate.
  • Oxidative reactions produce ribulose 5-phosphate, which can be converted into ribose 5-phosphate through non-oxidative reactions.
  • When the need for ribose exceeds NADPH, the non-oxidative reactions produce ribose from glycolytic intermediates.

NADPH Uses

  • Serves in reductive biosynthesis (synthesis of fatty acids, amino acids, and steroids).

Reactive Oxygen Species (ROS)

  • Formed from the partial reduction of molecular oxygen.
  • ROS (like superoxide, hydrogen peroxide, hydroxyl radical) are continuously produced.
  • This occurs as by-products of aerobic metabolism, toxic environmental substances, and reduced antioxidant levels.
  • ROS damages DNA, proteins, and lipids, leading to cellular damage and disease.

NADPH and ROS Reduction

  • NADPH provides reducing equivalents for processes like glutathione reductase to reduce hydrogen peroxide.
  • It is needed and produced by the pentose phosphate pathway for effective detoxification of reactive oxygen species (ROS).

Phagocytosis and Respiratory Burst

  • NADPH oxidase reduces oxygen in phagocytic cells to make superoxide (O2-), a toxic free radical that kills bacteria.
  • Superoxide is converted to more reactive ROS (like hydrogen peroxide).
  • H2O2, in presence of chloride ions and myeloperoxidase (MPO), kills bacteria by forming hypochlorous acid.
  • Peroxide can reduce to the hydroxyl radical and then reduced to water with catalase and glutathione peroxidase.

Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency

  • G6PD catalyzes the initial, irreversible oxidation of glucose 6-phosphate.
  • The deficiency impairs NADPH production in erythrocytes, leading to hemolysis (destruction of red blood cells).
  • Oxidative stress, certain drugs (e.g., antimalarials, antibiotics), fava beans, and infections are precipitating factors in G6PD deficiency.

G6PD Deficiency: Effects

  • Diminished NADPH production leads to impaired regeneration of the reduced glutathione pool.
  • Reduced detoxification of free radicals and peroxides leads to damage within cells.
  • Increased membrane fragility especially in RBC leading to hemolysis (RBC rupture).

G6PD Deficiency: Precipitating factors

  • Oxidant drugs: Antibiotics, Antimalarials, Antipyretics
  • Favism: Related to Mediterranean diet containing fava beans
  • Infections: Trigger the generation of free radicals within macrophages which diffuse to RBC and cause oxidative damage

G6PD Deficiency: Important roles of the enzyme

  • The only means of NADPH production in the erythrocytes.
  • The erythrocyte lacks nucleus and ribosomes so cannot renew the enzyme supply.
  • Erythrocytes carry oxygen in hemoglobin and thus, are more susceptible to ROS.
  • Muscle cannot replenish ribose 5P if the first two phases of HMP are deficient; ribose 5P is provided by the reverse of HMP phase 2 from glycolytic products.

PPP and Ribose-5-Phosphate

  • Ribose-5-phosphate is needed for nucleic acid biosynthesis.
  • Ribose is a critical component for nucleotides, further leading to DNA and RNA synthesis.
  • The HMP shunt is very important for providing ribose 5-phosphate in cells that produce a high rate of nucleotides and nucleic acids.

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Pentose Phosphate Pathway PDF

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Explore the intricacies of the HMP shunt and the Pentose Phosphate Pathway (PPP) through this quiz. Understand the role of NADPH and the synthesis of ribose 5-phosphate in cellular metabolism. Test your knowledge on the steps and functions of this critical metabolic pathway.

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