Biochemical Pathways

Biochemical or metabolic pathways can be explained as a step by step series of interconnected biochemical reactions and each step is catalysed by a specific enzyme.  Whilst these chemical reactions are carried out by a specific enzyme, the substrate is converted to a product which acts as a substrate for subsequent reactions. Thus substrates are being continuously converted into metabolic intermediates eventually producing  a final product. An important function of these pathways is to maintain homeostasis of the organism and to keep it alive.

Approximately 1300 enzymes are found in the human cell and these enzymes are coded by a different gene. Metabolism takes place when these enzymes work synchronously resulting in chemical reactions taking place at the rate of 37000 billion times billion per second in the human body. These biochemical catalysts (enzymes) play a critical role as they are the only ones who are capable of making small minute changes to a molecular layer by either breaking a bond or making a bond.

The Role of Enzymes in Metabolic Pathways

Below are various enzymatic control of metabolic pathways are:

Regulation of Glycolysis: Glycolysis is regulated at three enzymes: 

• Hexokinase: It is hindered by glucose-6-Phosphate 

• Phosphofructokinase: It is hindered by citrate and ATP 

• Pyruvate Kinase: This is hindered by ATP, alanine, free fatty acids and acetyl-CoA.

Regulation of Gluconeogenesis: The regulation of flow in gluconeogenesis/ gluconeogenesis is by Pyruvate carboxylase. It activated by acetyl-CoA, which signals the abundance of citric acid cycle intermediates, i.e., a decreased need for glucose

Regulation of Citric Acid Cycle: The primary enzyme that regulates the Krebs or the citric acid cycle is Pyruvate dehydrogenase. It is hindered by its products, NADH and acetyl-CoA.

Citrate Synthase: Hindered by its product, citrate. It is also restrained by intermediates of the TCA cycle at a high level such as succinyl-CoA and NADH.

Isocitrate dehydrogenase and alpha-ketoglutarate dehydrogenase such as citrate synthase, are inhibited by NADH and succinyl-CoA.

• Regulation of the urea acid cycle.

• Regulation of fatty acid metabolism.

• Regulation of pentose phosphate pathway.

Arrangement of Metabolic Pathways can be Any of the Following:

Linear Pathways –  It involves the conversion of one compound through a series of intermediates to another compound. An example would be glycolysis, where glucose is converted to pyruvate.

Branched Divergent Pathway – It is a type of pathway in which an intermediate can enter several linear pathways to different end products. Biosynthesis of purines and of some amino acids are examples of divergent pathways. A certain amount of regulation happens at this point. Branched Convergent as in several precursors which can give rise to a common intermediate. The conversion of various carbohydrates into the glycolytic pathway would be an example of convergent pathways.

Cyclic Pathway forms a closed loop. In the Citric acid cycle, an acetyl group is oxidised via a reaction that regenerates the intermediates in the cycle is a pathway resulting in some intermediates acting catalytically. The TCA is an example of a cyclic pathway.

Spiral pathway- The same set of enzymes catalyse a progressive lengthening of an acetyl chain.

Being multistep, these pathways allow regulation mechanisms to activate one pathway while inhibiting another. The regulation of the metabolites is necessary depending on the needs of the cell and the availability of the substrate. The end product of a pathway can be used immediately, can be used to initiate another metabolic pathway or it may be stored for use later.

Classification of Metabolic Pathways:

Metabolic pathways can be primarily classified into three types:

1. Anabolic pathways

2. Catabolic pathways

3. Amphibolic pathways

Anabolic Pathways

In this type of biochemical pathway, energy is required to form bonds. The reactants, intermediates and products utilised in the reaction are jointly called metabolites. The chemical reactions carried out are concerned with building up or production of complex macromolecules from simpler micro molecules.

A typical example is the synthesis of sugar (glucose from H2O and CO2). Other examples include the synthesis of fatty acids from acetyl CoA, synthesis of larger proteins from amino acids and synthesis of new DNA strands from nucleotides. These reactions are energy demanding which is provided by ATP and other high energy molecules such as NADH and NADPH. The energy that is taken up will be stored in the C-C bond of larger molecules.

List of Examples for Major Anabolic Pathways:

• Photosynthesis 

• Gluconeogenesis 

• Protein biosynthesis

• Fatty synthesis

• Pentose phosphate pathway

Catabolic Pathways

These types of catabolic pathways have chemical reactions involving the breaking down of complex macromolecules into micro molecules and hence the release of a large amount of bond energy. An example is the breakdown of sugar. When these reactions occur, energy stored in covalent bonds such as C-C bonds will get released.

Examples of Catabolic Pathways:

• Glycolysis

• TCA cycle

• Oxidative phosphorylation 

• Beta oxidation of fatty acid

• Urea cycle

• Glycogenolysis

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Amphibolic Pathways

Amphibolic pathways are either circular or linear. The intermediate in the pathway can be the starting point of another pathway. As an example, the breakdown of respiratory substrates such as proteins, glucose and fatty acids.

When glucose acts as a respiratory substrate, it is oxidised to pyruvate and then to acetyl CoA. Also, beta-oxidation of fatty acid results in the formation of acetyl-CoA. When protein undergoes degradation, it forms either pyruvate or acetyl-CoA. However, when the cell needs to prepare glucose or fatty acid or protein, either acetyl CoA or pyruvate can be withdrawn from the catabolic pathway and diverted for the synthesis of glucose or fatty acids or amino acid.

Hence, there is always an existence of a link between the anabolic and the catabolic process, it would be considered the respiratory pathway is amphibolic.

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Feedback Mechanism

• The feedback mechanism is important as it is the only way it can avoid wasting energy in making end-products that are already in plenty.

• The process is carried out when the final product of a pathway controls the rate of its synthesis through inhibition of its first step.

• Enzyme inhibition starts when an inhibitor fixes itself to the active site of the enzyme and the substrate cannot bind to the enzyme. This stalls the sequence of the metabolic pathway.

• The inhibitor denatures the enzyme so that it cannot work anymore, but the binding is temporary. As soon as the inhibitor disengages the enzymes go back to its active shape and continue to work on this substrate and the pathways open up once again.

• It is this way, homeostasis is maintained concerning the amount of end product that is produced.

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