Chapter 20 Pentose Phosphate pathway

When the cell needs for Ribose 5 phosphate = NADPH

2 NADPH and 1 Ribose is produced. (During oxidation step. Normal PPP)

transketolase transfer

2 carbon unit

transaldolase transfers

3 carbon unit

The oxidative phosphorylation of 6-phosphogluconate to ribulose 5-P. It produces NADPH.

6 Phosphogluconate Dehydrogenase

hydrolyzes 6-Phosphogluconolactone IRREVERSIBLY to 6-Phosphogluconate. (Step 2)

6-Phosphogluconolactonase

Describe the distinct parts of the PPP and articulate the importance of each part?

A. There are two distinct phases: Oxidative and Non-Oxidative. B. The Oxidative Phase involves the oxidation of glucose 6-phosphate (6C) to ribulose 5-phosphate (5C) producing 2 NADPH. The irreversible oxidative segment of the pentose phosphate pathway is composed of three sequential reactions that generate ribulose 5-phosphate, NADPH and release CO2. Glucose 6-Phosphate dehydrogenase, and 6-Phosphogluconate dehydrogenase are two reactions that produce NADPH. C. Glucose 6- Phosphate Dehydrogenase (G-6-P DH) is the Rate Limiting Step. It is highly specific for NADP+ and is the Primary regulation point. It is strongly inhibited by NADPH. Defects in this enzyme, represents a common enzymopathy known as Favism. Individuals affected suffer from hemolytic anemia. D. 6 Phosphogluconate Dehydrogenase: The oxidative phosphorylation of 6-phosphogluconate to ribulose 5-P. It produces NADPH. E. 6-Phosphogluconolactonase hydrolyzes 6-Phosphogluconolactone IRREVERSIBLY to 6-Phosphogluconate. (Step 2) F. The Non Oxidative Reversible Phase: The interconversion (rearrangement) of Ribulose5-Phosphate with Ribose 5 Phosphate or Xylulose 5- Phosphate- 5C sugars. The enzymes responsible for this rearrangement are transketolase and transaldolase. The rearrangement of Ribose 5- Phosphate is by transketolase (transfers a 2- Carbon unit). Transaldolase (Transfers a 3- Carbon Unit) Ketose to Aldose.

Discuss the major functions of the PPP including the provision of Ribose5P for the biosynthesis of nucleotides.

A. To provide NADPH for biosynthesis of FA, cholesterol, NT and reduction of oxidized Glutathione. B.To provide pentose for nucleic acid synthesis and to provide a pathway for the synthesis and degradation of pentose to glycolytic intermediates.

Distinguish between the reactions catalyzed by transketolase and transaldolase?

A.Both are Ketose to Aldose. Transketolase transfers a 2C unit and requires TPP as a cofactor and is Mg ++ dependent. B.Transaldolase transfers a 3C unit and works independently of TPP.

Describe the changes that take place in the interconversion of the pentose sugars Ribose5P and Xylulose5P.

A.Oxidative phase is followed by an isomerization and epimerization phase in which ribulose 5-phosphate is converted to ribose 5-phosphate, a component of numerous molecules of considerable biochemical significance or xylulose 5-phosphate that has minimal significance in mammals. B.The isomerization and epimerization phase and the rearrangement phase can be considered together as the non-oxidative phase of the pathway. The pathway terminates in a rearrangement phase in which two molecules of xylulose 5-phosphate and one molecule of ribose 5-phosphate are converted to two molecules of fructose 6-phosphate and one molecule of glyceraldehyde 3-phosphate (both glycolytic intermediates).

Review how the flow of Glucose6P through the pathway is governed by the situation that prevails within the cell?

A.When the cell needs for Ribose 5 Phosphate>NADPH: the cells are rapidly dividing. Fructose 6- phosphate and glyceraldehyde 3- Phosphate are converted to 3-ribose 5- phosphate, by transketolase and transaldolase. B.When the cell needs for Ribose 5 phosphate = NADPH: 2 NADPH and 1 Ribose is produced. (During oxidation step. Normal PPP) C.When the cell needs NAPDH>Ribose 5 phosphate AND ATP is required Ribose 5- Phosphate is converted to Pyruvate, + NADPH & ATP D.When the cell needs NAPDH>Ribose 5 phosphate (This is when adipose tissue, is generating fatty acids). Glucose-6-phosphate, is completely oxidized to CO2 NADPH + Ribulose-5-phosphate. It is then converted to ribose 5 phosphate. Glycerol 3 phosphate & fructose 6 phosphate (which regenerates glucose 6 phosphate by gluconeogenesis enzymes) This process, allows ribose-5- phosphate to be recycled through PPP. Example is actively producing steroid hormones in the adrenal cortex.

Explain the pathogenesis of hemolytic anemia due to Glucose6P DH deficiency?

Affected individuals with the deficiency are protected against malaria. Defects in this enzyme-affected individuals suffer from poor erythrocyte health manifesting as hemolytic anemia. The condition is brought on by consumption of fava beans or exposure to certain medications though they may be more resistant to malarial infection. Mutant enzyme is rapidly degraded and RBC (lacking a nucleus) cannot re-synthesize it.

Describe the pentose phosphate pathway?

An important pathway occurring within the cytoplasm of mammalian cells. It is central to the formation of NADPH and responsible for the synthesis and degradation of pentose

is the Rate Limiting Step. It is highly specific for NADP+ and is the Primary regulation point. It is strongly inhibited by NADPH. Defects in this enzyme, represents a common enzymopathy known as Favism. Individuals affected suffer from hemolytic anemia.

Glucose 6- Phosphate Dehydrogenase

Articulate how the PPP is regulated?

Glucose6P DH regulates the pathway. It is the RATE LIMITING STEP. It is highly specific for NADP+ and it is the primary regulation point. NADPH inhibits it.

Explain the biological important of Glutathione

Glutathione possesses a free sulfhydryl group that protects against highly reactive damaging oxidizing agents.

Rationalize the tissue distribution of the PPP?

Pathway activity is most significant in tissues that have a high NADPH requirement such as the liver, mammary gland, adrenal cortex, kidney, and adipose tissue and RBCs; the major sites of FA and steroid biosynthesis.

Evaluate the role of Glutathione Reductase?

Reduced Glutathione is produced in a reaction catalyzed by Glutathione Reductase, a NADPH requiring enzyme. The production of NADPH and reduced Glutathione may provide protection from cancer and serve to maintain the integrity of the RBC membrane

When the cell needs NAPDH>Ribose 5 phosphate AND ATP is required

Ribose 5- Phosphate is converted to Pyruvate, + NADPH & ATP

The interconversion (rearrangement) of Ribulose5-Phosphate with Ribose 5 Phosphate or Xylulose 5- Phosphate- 5C sugars. The enzymes responsible for this rearrangement are transketolase and transaldolase. The rearrangement of Ribose 5- Phosphate is by transketolase (transfers a 2- Carbon unit). Transaldolase (Transfers a 3- Carbon Unit) Ketose to Aldose.

The Non Oxidative Reversible Phase

for the interconversion of the pentose sugars Ribose5P and Xylulose5P is followed by the rearrangement phase can be considered together as the non-oxidative phase of the pathway. The pathway terminates in a rearrangement phase in which two molecules of xylulose 5-phosphate and one molecule of ribose 5-phosphate are converted to two molecules of fructose 6-phosphate and one molecule of glyceraldehyde 3-phosphate (both glycolytic intermediates).

The isomerization and epimerization phase

involves the oxidation of glucose 6-phosphate (6C) to ribulose 5-phosphate (5C) producing 2 NADPH. The irreversible oxidative segment of the pentose phosphate pathway is composed of three sequential reactions that generate ribulose 5-phosphate, NADPH and release CO2. Glucose 6-Phosphate dehydrogenase, and 6-Phosphogluconate dehydrogenase are two reactions that produce NADPH

The oxidative phase

When the cell needs NAPDH>Ribose 5 phosphate

This is when adipose tissue, is generating fatty acids). Glucose-6-phosphate, is completely oxidized to CO2 NADPH + Ribulose-5-phosphate. It is then converted to ribose 5 phosphate. Glycerol 3 phosphate & fructose 6 phosphate (which regenerates glucose 6 phosphate by gluconeogenesis enzymes) This process, allows ribose-5- phosphate to be recycled through PPP. Example is actively producing steroid hormones in the adrenal cortex.

for the interconversion of the pentose sugars Ribose5P and Xylulose5P is followed by an isomerization and epimerization phase in which ribulose 5-phosphate is converted to ribose 5-phosphate, a component of numerous molecules of considerable biochemical significance or xylulose 5-phosphate that has minimal significance in mammals.

non oxidative phase

When the cell needs for Ribose 5 Phosphate>NADPH

the cells are rapidly dividing. Fructose 6- phosphate and glyceraldehyde 3- Phosphate are converted to 3-ribose 5- phosphate, by transketolase and transaldolase