Introduction to metabolism

Introduction to metabolism:

Hundreds of reactions simultaneously take place in a living cell, in a wee-organized and integrated manner. The entire spectrum of the chemical reactions. Occurring in the living system, are collectively referred to as metabolism.

A metabolic pathway ( metabolic map) constitutes a series of enzymatic reactions to produce specific products. The term metabolite is applied to the substrate or an intermediate or a product in the metabolic reactions.

Metabolism is broadly divided into two categories:

1. Catabolism:The degradative processes concerned with the breakdown of complex molecules to simpler ones, with a concomitant release of energy.
2. Anabolism:The biosynthetic reactions involving the formation of complex molecules from the simple precursor.

A clear demarcation between catabolism and anabolism is rather difficult since there are several intermediates which are common to both the processes. The term amphibolism is also in use for reactions which are both catabolic and anabolic in nature.

Catabolism:

The very purpose of catabolism is to trap the energy of the biomolecules in the form of ATP and generate the substances (precursors) required for the synthesis of complex molecules. Catabolism occurs in three stages:

1. Conversion of complex molecules into their building blocks: polysaccharides are broken down to monosaccharides, lipids to free fatty acids and glycerol, proteins to amino acids.
2. Formation of simple intermediates: the building blocks produced in stage first are degraded to simple intermediates such as pyruvate and acetyl CoA. These intermediates are not readily identifiable as carbohydrates, lipids or proteins. A small quantity of energy (as ATP) is captured in stage 2.
3. Final oxidation of acetyl CoA: acetyl CoA is completely oxidized to CO₂, liberating NADH and FADH₂ that finally get oxidized to release the large quantity of energy (as ATP). Krebs cycle (or citric acid cycle) is the common metabolic pathway which involved in the final oxidation of all energy-rich molecules. This pathway accepts carbon compounds (pyruvate, succinate, etc.) derived from carbohydrates, lipids or proteins.

Anabolism:

For the synthesis of a large variety of complex molecules, the starting materials are relatively few. These include pyruvate, acetyl CoA, and intermediates of citric acid cycle. Besides the availability of precursors, the anabolic reactions are dependent upon the supply of energy (as ATP or GTP) and reducing equivalents (as NADPH + H⁺).

The anabolic and catabolic pathways are not reversible and are operate independently. as such, the metabolic pathways occur in specific cellular locations are mitochondria, microsomes, etc. and are controlled by different regulatory signals.

The terms intermediary metabolism and energy metabolism are in use. Intermediary metabolism refers to the entire range of catabolic and anabolic reactions, not involving nucleic acids. Energy metabolism deals the metabolic pathways concerned with the storage and liberation of energy.

Types of metabolic reactions:

The biochemical reactions are mainly of four types

1. Oxidation-reduction
2. Group transfer
3. Rearrangement and isomerization
4. Make and break of carbon-carbon bonds.

These reactions are catalyzed by the specific enzymes more than 2000 known so far.

Methods employed to study metabolism:

The metabolic reactions do not occur in isolation. Which are interdependent and integrated into specific series that constitute metabolic pathways. Therefore it is not an easy task to study metabolisms. Fortunately, the basic metabolic pathways in most organisms are essentially identical. For this reason, many organisms can be used to understand metabolisms.

Several methods are employed to elucidate biochemical reactions and the metabolic pathways. These experimental approaches may be broadly divided into 3 categories:

1. Use of whole organisms or its components.
2. The utility of metabolic probes.
3. Application of isotopes.

The actual methods employed may be either in the Vivo (in the living system) or in vitro (in the test tube) or, more frequently, both.

1. Use of whole organism or its components:
2. Whole organism: The ultimate aim of a biochemist is to know the metabolism in the organism as a whole. Glucose tolerance test (GTT) employed to measure the response of man (or other animals) towards carbohydrate metabolism is a good example of the use of the whole organism.
3. Isolated organs, tissue slices, whole cells: subcellular organelles, cell-free system and recently purified components are frequently used to elucidate biochemical reactions and metabolic pathway.
4. Utility of metabolic probes:

Two types of metabolic probes are commonly used to trace out biochemical pathways. These are metabolic inhibitors and mutations. In both the cases, there is a specific blockade in a metabolic reaction which helps to understand the pathway. Inhibitors of electron transport chain have been largely responsible for elucidating the sequence of electron carriers. The inborn errors of metabolism in higher organisms and the genetic manipulations in the microorganisms have also contributed a lot to the understanding of metabolism.

Application of isotopes:

Isotopes are the atoms with the same number of protons but different neutrons. By use isotopes, the molecules of the living system can be labelled without altering their chemical properties. Application of isotopes in biochemistry has revolutionised the study of metabolisms. More details on the utility of isotopes in biochemistry are given elsewhere.

References

Michael J.Pleczar JR, Chan E.C.S. and Noel R. Krieg. Microbiology. Tata Mc GrawHill, 1993.

Powar. and Daginawala. General Microbiology.

Rangaswami and Bagyaraj D.J. Agricultural Microbiology.

Debey, RC and D K Maheshwari. A textbook of Microbiology. India: s.chand and company Ltd., 1999.