Table Of Contents
- Enzymatic Control Of Metabolic Pathways
- Types Of Biochemical Pathways
- Regulation of Metabolic Pathways
Biochemical pathways or metabolic pathway is a step by step series of interconnected biochemical reactions in which each step is catalyzed by a specific enzyme. During the series of chemical reaction, substrate is converted into product that in turn acts as a substrate for subsequent reaction. Thus a molecule(s) or substrate(s) are being continuously converted into metabolic intermediates eventually yielding a final product(s).
Biochemical pathways are synonymous with metabolic pathways. The word metabolism comes from a Greek word “metabole” which means change referring to all the chemical reactions that occur inside the organism’s body. These pathways are necessary for maintaining the homeostasis of the organism and to keep it alive.
So essentially, these pathways consist of a series of enzyme- activated reactions where the product of one reaction becomes the substrate for the next reaction to follow.
Being multistep, these pathways allow regulation mechanisms to activate one pathway and inhibit another.
Now there are approximately 1300 enzymes found in the human cell and each of 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 37 thousand billion times billion per second in the human body. 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.
Enzymatic Control Of Metabolic Pathways
A look at the various enzymatic control of metabolic pathways are-
- Regulation of glycolysis – Glycolysis can be regulated at three enzymes: Hexokinase: hindered by glucose-6-P (product inhibition), Phosphofructokinase: hindered by citrate and ATP and Pyruvate kinase: hindered by ATP, alanine, free fatty acids and acetyl-CoA.
- Regulation of gluconeogenesis – Regulation of flow by Pyruvate carboxylase (activated by acetyl-CoA, which signals the abundance of citric acid cycle intermediates, i.e., a decreased need of glucose).
- Regulation of citric acid cycle – Pyruvate dehydrogenase: hindered by its products, NADH and acetyl-CoA
Citrate synthase: hinderd 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 a-ketoglutarate dehydrogenase: like citrate synthase, these 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 – 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 – is one such where 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 reaction that regenerates the intermediates in the cycle is a pathway resulting in some intermediates acting in a catalytic fashion. The Tricarboxylic Acid Cycle is an example of a cyclic pathway.
- Spiral pathway- The same set of enzymes catalyze 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.
Types Of Biochemical Pathways
There are basically two types of biochemical pathways:
- Anabolic pathways
- Catabolic pathways.
It is a biosynthetic pathway wherein energy is required to form bonds. The pools of reactants, intermediates and products are jointly called metabolites. The chemical reactions occurring are concerned with building up or production of larger, complex macromolecules from simpler micro molecules. Typical example is the synthesis of sugar (glucose from CO2 and H2O). Other examples include synthesis of fatty acids from acetyl CoA, synthesis of larger proteins from amino acid building blocks, and synthesis of new DNA strands from nucleotides. These reactions constantly take place in the cell and are critical to the survival of the cell. These reactions demand input of energy which is provided by adenosine triphosphate (ATP) and other high energy molecules such as nicotinamide adenine dinucleotide (NADH) and nicotinamide adenine dinucleotide phosphate (NADPH). The up taken energy will be stored in the C-C bond of larger molecules.
List of examples for major anabolic pathways:
- Photosynthesis (synthesis of glucose from CO2 and H2O)
- Pentose phosphate pathway (synthesis of pentoses and release of reducing power needed for anabolic reactions)
- Gluconeogenesis (synthesis of glucose from non carbohydrate sources, mainly used by brain)
- Protein Biosynthesis
- Fatty acid synthesis
- Glycogenesis (synthesis of glycogen primarily from glucose occurs in liver and muscle)
These pathways have chemical reactions involve the breaking down of complex macromolecules into simpler, micro molecules and hence the release of a large amount of bond energy. A typical example is breakdown of sugar (glucose into CO2 and H2O). During these reactions, energy stored in covalent bonds such as C-C bonds will get released. These pathways can also operate on energy-storing molecules like lipids and glycogen to release energy and make ATP.
List of examples for catabolic pathways:
- Glycolysis (breakdown or oxidation of glucose)
- Kreb’s cycle or Tricarboxylic acid cycle or citric acid cycle (oxidation of acetyl CoA)
- Oxidative phosphorylation (disposal of electrons released by glycolysis and TCA cycle)
- Beta oxidation of fatty acid (the breakdown of fatty acid into acetyl CoA)
- Urea cycle (disposal of Ammonia obtained from deamination of amino acid)
- Glycogenolysis (breakdown of glycogen into glucose).
There are a very large number of biochemical pathways occurring in humans. Majority of these metabolic reactions do not occur in isolation but are linked to some other reactions. These pathways are either linear or circular. The intermediate of one pathway (metabolite) can also act as a starting point of another pathway. For example, the breakdown of respiratory substrates like glucose, protein and fatty acids.
When glucose acts as a respiratory substrate, it initially oxidizes to pyruvate, then to acetyl CoA. Similarly, beta-oxidation of fatty acid leads to the formation of acetyl CoA. When protein undergoes degradation, it forms either pyruvate or acetyl CoA. But, when the cell needs to prepare glucose or fatty acid or protein, any of these pyruvate or acetyl CoA 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 synthesis process (Anabolic) and breakdown process (Catabolic), it would be considered the respiratory pathway as an amphibolic pathway.
Regulation of Metabolic Pathways
To maintain a living status, cells and organisms always persist in a dynamic steady state, and not to attain equilibrium with their surroundings. This means at the molecular level, that for each metabolic reaction in a pathway, the substrate is provided by the preceding reaction at the same rate at which it is converted to product. Thus, even though the rate of metabolite or flux is altered (either increased or decreased) the substrate S concentration remains constant. This is known as steady-state.
Due to some change in external circumstances, there tends to be a temporary disturbance in the steady-state. In order to maintain the dynamic steady state, the system itself triggers regulatory mechanisms intrinsic to each pathway. The net effect of all these adjustments is to return the organism to a new steady-state—to achieve homeostasis.
To be simple in other words, biochemical pathways interact in a complex way in order to allow adequate regulation. Reactions are turned on and off or sped up and slowed down according to the cell’s immediate needs and overall functions. Living systems have two exquisite mechanisms for regulating the cell’s metabolism to be in homeostatic condition. One is enzymatic control (Since flux through a biochemical pathway depends on the activities of the enzymes that catalyze each reaction in that pathway) and another is hormonal control.
- Feedback mechanism is necessary because it is only in this way it can avoid wasting energy in making end- products that are already in plenty.
- Feedback inhibition occurs when the final product of a pathway controls the rate of its own synthesis through inhibition of its first step.
- Enzyme inhibition means to stop the enzyme from working. An inhibitor fixes itself to the active site of the enzyme and prevents the substrate from binding itself, thus stalling the sequence of the metabolic pathway. It is only a conformational change.
- The inhibitor only denatures the enzyme so that it cannot work anymore, but the binding is temporary. As soon as the inhibitor disengages, the enzyme goes back to its active shape and continues to work on this substrate and the pathways open up once again.
- It is this way, homeostasis is maintained with respect to the amount of end product that is produced.
Impact Of Mutation On Translation Into Amino Acids
Sometimes, mutation within a gene happens when there are changes in the base sequence which determines the amino acid sequence. This results in the substrate becoming unable to bind to the active site. This results in no enzyme complexes that can be formed. This leads to a myriad of metabolic disorders.
A typical biochemical pathway
Key compounds that enter the pathway are:
- Glucose from carbohydrates
- Amino acids from proteins
- Fatty acids and glycerol from lipids but each enters the pathway through different routes. Glucose follows the entire pathway in a linear manner.
Glucose And Anaerobic Respiration
Let us see what happens when a glucose molecule undergoes anaerobic respiration to produce 2 moles of ATP. Remember that glycolytic enzymes are present within the cytoplasmic matrix.
1st step – shows the phosphorylation of glucose by ATP and enzyme hexokinase. Clearly this is an energy “in “phase where ATP loses its energy bonds and is reduced to ADP. This reaction is energy-dependent and occurs one way.
2nd step – Glucose -6–phosphate undergoes isomeric transformation to become fructose -6- phosphate by the enzyme phospho hexoisomerase.
3rd step – Fructose 6 phosphate is phosphorylated by ATP to fructose -1, 6 bisphosphate by the enzyme phosphofructokinase and ADP is formed. This reaction is again Mg2+ dependent and again one way.
4th step – Enzyme aldolase cleaves Fructose -1, 6- bisphosphate into two compounds Glyceraldehyde 3 phosphate [G3P] and Dihydroxyacetone phosphate [DHAP]. Part of DHAP gets converted to G3P by the mediation of enzyme phosphotriose isomerase.
5th step – G3P pathway to glycolysis is direct. However DHAP is not. Hence Triose-phosphate isomerase converts DHAP into GAP which is useful for generating ATP. This results in glucose being cleaved into 2 molecules of glyceraldehyde -3-phosphate through a rapid and reversible reaction.
6th step – Oxidative phosphorylation of G3P to 1,3-Bisphosphoglycerate.
7th step – 1,3 – Bisphosphoglycerate converts into 3 – Phosphoglycerate. Transfer of phosphoric acid to ADP occurs leading to formation of ATP in the presence of enzyme Phosphoglycerate kinase.
8th step -3 phosphoglyceric acid is again acted upon by Phosphoglycerate mutase to obtain 2-phosphoglyceric acid.
9th step -This compound is catalyzed by anhydrous endolase which absorbs one molecule of water before the reaction starts to yield 2 phospho phenol pyruvic acid and the same molecule of water is released after the reaction.
10th step – Lastly in the presence of Pyruvate kinase, 2 -phosphoenol pyruvic acid and ADP yields Pyruvic acid and ATP.
1. What are biochemical reactions?
Biochemical pathways or metabolic pathway is a step by step series of interconnected biochemical reactions in which each step is catalyzed by a specific enzyme. During the series of chemical reaction, the substrate is converted into a product that in turn acts as a substrate for subsequent reaction. Thus a molecule(s) or substrate(s) are being continuously converted into metabolic intermediates eventually yielding a final product(s).
2. Write about anabolic reactions.
The chemical reactions that result in the building up of or production of larger, complex macromolecules from simpler micro molecules are called anabolic reactions. These reactions are constantly taking place in the cell and are critical to the survival of the cell. These reactions demand the input of energy which is provided by adenosine triphosphate (ATP) and other high energy molecules such as nicotinamide adenine dinucleotide (NADH) and nicotinamide adenine dinucleotide phosphate (NADPH). The up taken energy will be stored in the C-C bond of larger molecules.
3. Write about catabolic reactions.
The chemical reactions that lead to breaking down of complex macromolecules into simpler, micro molecules are called catabolic reactions. Typical example is the breakdown of sugar (glucose into CO2 and H2O). During these reactions, energy stored in covalent bonds such as C-C bonds will get released. These pathways can also operate on energy-storing molecules like lipids and glycogen to release energy and make ATP.
4. What is amphibolic pathway?
The pathway in which both anabolic and catabolic reactions are taking place is called anabolic pathway. In amphibolic pathway, the reaction intermediates or metabolites of catabolic pathway can also acts as a precursor for any anabolic pathway. Example: TCA cycle.
5. How biochemical pathways are regulated?
There are inherent complex ways by which the metabolic pathways are adequately regulated. Reactions are turned on and off or sped up and slowed down according to the cell’s immediate needs and overall functions. Living systems have two exquisite mechanisms for regulating the cell’s metabolism to be in homeostatic condition. One is enzymatic control (Since flux through a biochemical pathway depends on the activities of the enzymes that catalyze each reaction in that pathway) and another is hormonal control.
6. If the biochemical pathways remain unregulated, then
(a)The rate of breakdown of metabolites will get disturbed
(b)Homeostasis cannot be maintained
(c)Will lead to steady-state or dynamic equilibrium
(d)Will lead to a host of metabolic disorders
Solution: Both options (b) and (d)
7. In the feedback mechanism,
(a)The final product controls the rate of its own synthesis from the middle of the pathway
(b)The consequent product of the same pathway controls the rate of its own synthesis
(c)The enzyme gets denatured permanently so that the substrate cannot bind anymore
(d)The final product of a pathway controls the rate of its own synthesis through inhibition of its first step.
Solution: (d)The final product of a pathway controls the rate of its own synthesis through inhibition of its first step.
8. The inter convertibility of G3P and DHAP could not have been possible had it not been for catalyzation of
(a)Phospho hexose isomerase
(d)Trio phosphate Isomerase (TPI)
Solution: (d)Trio phosphate Isomerase (TPI)
9. This is a metabolic pathway where through a series of chemical reactions by all aerobic organisms, acetyl-CoA is oxidised to release energy stored in the bonds from carbohydrates, proteins and fats, into carbon dioxide and bond energy in the form of adenosine triphosphate (ATP). It maintains a __________pathway.
(a)Urea Acid cycle, circular
(b)Citric Acid cycle or Krebs cycle, circular
(c)Fatty Acid metabolism, circular
(d)Pentose phosphate pathway, linear
Solution: (b)Citric Acid cycle or Krebs cycle, circular
10. Situation, where no enzyme complexes can be formed, can be because
(a)Of gene mutation
(b)Extensive changes in the base sequence which determines the amino acid sequence
(c)The substrate not being able to bind to the active site
(d)All the above
Solution: (d)All the above
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