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Theory of Intelligent Design, the best explanation of Origins » Molecular biology of the cell » Metabolism » The pentose phosphate pathway

The pentose phosphate pathway

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1 The pentose phosphate pathway on Thu Aug 27, 2015 10:13 am

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The pentose phosphate pathway 1

The PPP has gained recognition as being a central player in cellular biosynthetic metabolism and in controlling and maintaining the redox homeostasis of cells

The pentose phosphate pathway is the major source for the NADPH required for anabolic processes.3 There are three distinct phases each of which has a distinct outcome. Depending on the needs of the organism the metabolites of that outcome can be fed into many other pathways. Gluconeogenesis is directly connected to the pentose phosphate pathway. As the need for glucose-6-phosphate (the beginning metabolite in the pentose phosphate pathway) increases so does the activity of gluconeogenesis.

Introduction
The main molecule in the body that makes anabolic processes possible is NADPH.  Because of the structure of this molecule it readily donates hydrogen ions to metabolites thus reducing them and making them available for energy harvest at a later time. The PPP is the main source of synthesis for NADPH.  The pentose phosphate pathway (PPP) is also responsible for the production of Ribose-5-phosphate which is an important part of nucleic acids. Finally the PPP can also be used to produce glyceraldehyde-3-phosphate which can then be fed into the TCA and ETC cycles allowing for the harvest of energy. Depending on the needs of the cell certain enzymes can be regulated and thus increasing or decreasing the production of desired metabolites. The enzymes reasonable for catalyzing the steps of the PPP are found most abundantly in the liver (the major site of gluconeogenesis) more specifically in the cytosol. The cytosol is where fatty acid synthesis takes place which is a NADPH dependent process.

Oxidation Phase
The beginning molecule for the PPP is glucose-6-P which is the second intermediate metabolite in glycolysis.

The PPP and glycolysis are therefore interdependent.

Glucose-6-P is oxidized in the presence of glucose-6-P dehydrogenase and NADP+.  This step is irreversible and is highly regulated.  NADPH and fatty acyl-CoA are strong negative inhibitors to this enzyme.  The purpose of this is to decrease production of NADPH when concentrations are high or the synthesis of fatty acids is no longer necessary.  
The metabolic product of this step is gluconolactone which is hydrolytrically unstable.  Gluconolactonase causes gluconolactone to undergo a ring opening hydrolysis.  The product of this reaction is the more stable sugar acid, 6-phospho-D-gluconate.
6-phospho-D-gluconate is oxidized by NADP+ in the presence of 6-phosphogluconate dehydrogenase which yields ribulose-5-phosphate.
The oxidation phase of the PPP is solely responsible for the production of the NADPH to be used in anabolic processes.

Isomerization Phase
Ribulose-5-phosphate can then be isomerized by phosphopentose isomerase to produce ribose-5-phosphate.  Ribose-5-phosphate is one of the main building blocks of nucleic acids and the PPP is the primary source of production of ribose-5-phosphate. If production of ribose-5-phosphate exceeds the needs of required ribose-5-phosphate in the organism, then phosphopentose epimerase catalyzes a chiralty rearrangement about the center carbon creating xylulose-5-phosphate. The products of these two reactions can then be rearranged to produce many different length carbon chains.  These different length carbon chains have a variety of metabolic fates.

Rearrangement Phase
There are two main classes of enzymes responsible for the rearrangement and synthesis of the different length carbon chain molecules.  These are transketolase and transaldolase. Transketolase is responsible for the cleaving of a two carbon unit from xylulose-5-P and adding that two carbon unit to ribose-5-P thus resulting in glyceraldehyde-3-P and sedoheptulose-7-P. Transketolase is also responsible for the cleaving of a two carbon unit from xylulose-5-P and adding that two carbon unit to erythrose-4-P resulting in glyceraldehyde-3-P and fructose-6-P. Transaldolase is responsible for cleaving the three carbon unit from sedoheptulose-7-P and adding that three carbon unit to glyceraldehyde-3-P thus resulting in erythrose-4-P and fructose-6-P. The end results of the rearrangement phase is a variety of different length sugars which can be fed into many other metabolic processes.  For example, fructose-6-P is a key intermediate of glycolysis as well as glyceraldehyde-3-P.



Pentose Phosphate Pathway of Glucose Oxidation 2

In most animal tissues, the major catabolic fate of glucose 6-phosphate is glycolytic breakdown to pyruvate, much of which is then oxidized via the citric acid cycle, ultimately leading to the formation of ATP. Glucose 6-phosphate does have other catabolic fates, however, which lead to specialized products needed by the cell. Of particular importance in some tissues is the oxidation of glucose 6-phosphate to pentose phosphates by the pentose phosphate pathway (also called the phosphogluconate pathway or the hexose monophosphate pathway;



In this oxidative pathway, NADP is the electron acceptor, yielding NADPH. Rapidly dividing cells, such as those of bone marrow, skin, and intestinal mucosa, and those of tumors, use the pentose ribose 5-phosphate to make RNA, DNA, and such coenzymes as ATP, NADH, FADH2, and coenzyme A. In other tissues, the essential product of the pentose phosphate pathway is not the pentoses but the electron donor NADPH, needed for reductive biosynthesis or to counter the damaging effects of oxygen radicals. Tissues that carry out extensive fatty acid synthesis (liver, adipose, lactating mammary gland) or very active synthesis of cholesterol and steroid hormones (liver, adrenal glands, gonads) require the NADPH provided by this pathway. Erythrocytes and the cells of the lens and cornea are directly exposed to oxygen and thus to the damaging free radicals generated by oxygen. By maintaining a reducing atmosphere (a high ratio of NADPH to NADP and a high ratio of reduced to oxidized glutathione), such cells can prevent or undo oxidative damage
to proteins, lipids, and other sensitive molecules.


1) https://en.wikipedia.org/wiki/Pentose_phosphate_pathway
2) Lehninger Principles of Biochemistry fifth edition pg.558
3) http://chemwiki.ucdavis.edu/Biological_Chemistry/Metabolism/Pentose_Phosphate_Pathway

further readings :

https://mcb.berkeley.edu/labs/krantz/mcb102/lect_S2008/MCB102-SPRING2008-LECTURE5-PENTOSE.pdf



Last edited by Admin on Thu Aug 27, 2015 7:36 pm; edited 4 times in total

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2 PPP enzymes on Thu Aug 27, 2015 10:31 am

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Pentose phosphate pathway enzymes

Oxidative phase

Glucose-6-phosphate dehydrogenase
6-phosphogluconolactonase
Phosphogluconate dehydrogenase

Non-oxidative phase

Ribose-5-phosphate isomerase
Phosphopentose epimerase
Transketolase
Transaldolase



Non‐enzymatic glycolysis and pentose phosphate pathway‐like reactions in a plausible Archean ocean

The reaction sequences of central metabolism, glycolysis and the pentose phosphate pathway provide essential precursors for nucleic acids, amino acids and lipids. However, their evolutionary origins are not yet understood. 1

Here, we provide evidence that their structure could have been fundamentally shaped by the general chemical environments in earth's earliest oceans.  The 29 observed reactions include the formation and/or interconversion of glucose, pyruvate, the nucleic acid precursor ribose‐5‐phosphate and the amino acid precursor erythrose‐4‐phosphate, antedating reactions sequences similar to that used by the metabolic pathways.

Despite cellular organisms possess sophisticated metabolic capacities, the origin of the underlying metabolic network is only barely understood

Due to the complexity of the metabolic pathways, it has been argued that metabolism‐like chemical reaction sequences are unlikely to be catalysed by simple environmental catalysts



1) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4023395/

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