Transport Through Gap Junctions
Cell-to-cell transport is made possible through passage-ways connecting the interiors of the contagious cell (Fig.
7.22). These passageways span the intervening space, or gap between the apposed cells and hence, are termed the gap junctions, or cell-to-cell channels. All polar mole-cules with molecular weight of 1 kD or less can be trans-ported through gap junctions. They move along a concentration gradient by passive diffusion.
Structure: A transmembrane protein, known as con-nexin (MW 32 kD) is the major structural element of gap
Low pH
Fusion
Secondary lysosome Recycled receptor
Degraded ligand
New vesicle Endosome
Clathrin coated vesicles Coated pit
Hydroloses Lysosome
Fig. 7.21. Receptor-mediated endocytosis: action of LDL receptors (● ligand, receptor).
Intracellular space
Cytoplasm
Closed system Open system
Central hole
Connexin subunit
Membrane Membrane
Fig. 7.22. Gap junction connecting two opposed cells.
A 3-year-old child was brought to the hospital OPD with com-plaints of cough, diffi culty in breathing, and indigestion. He had recurrent episodes of infections of respiratory tract for which he was treated with antibiotics by his father, a general practitioner. The latter had noticed that during hot weather, acute salt deposition occurred on child’s skin. Moreover, a fond kiss left a salty taste in mouth, which he affectionately referred to as the ‘salty kiss’. A fi rst cousin of the child had somewhat similar signs and symptoms, though of a milder degree.
On examination, the child appeared weak and mal-nourished. Analysis of the sample obtained by rectal biopsy showed thick mucus, that was blocking various tubu-lar structures of the glands. The epithelial cells (obtained by biopsy) were cultured in appropriate medium, and transport of chloride ions across these cells was measured.
The results were compared with the chloride transport in epithelial cells of a normal subject. The transport in the patient was less than 5% of that in case of the normal sub-ject. 14C–PABA test, a tubeless pancreatic function test, was
performed. It showed decreased urinary elimination of the labeled compound which suggested impaired exocrine pancreatic activity. Chloride content of the sweat was markedly enhanced (88 mEq/L).
Q.1. Identify the biochemical defect in this child. Which clinical disorder does the above defect lead to?
Q.2. Provide a biochemical explanation for the signs and symptoms of the child.
Q.3. The CFTR protein was isolated from the airway. What changes are likely to be present in this protein?
Q.4. The CFTR protein of the patient was found missing in phenylalanine at the 358th position. However, the protein was found to be functionally active because when it was reconstituted with phospholipids to form lipo-some, the chloride transport across the latter was normal. Provide an explanation for the patients disease stated in spite of having a functionally nor-mal protein.
2. Describe the fl uid mosaic model.
3. Distinguish passive, facilitated, active- and secondary active-transport systems.
Write short notes on
1. Difference between integral and peripheral mem-brane proteins
2. Inophores 3. Na–K-Pump
4. Secondary active transport 5. Gap junctions
6. Lipid bilayer fl ow from one cell to another, thus ensuring a
cou-pled and quick response.
3. Current evidence suggests that the communicating channels are important for development and tissue differentiation.
Exercises
Essay type questions
1. What are liposomes? Mention their uses in biology and medicine.
C L I N I C A L C A S E
CASE 7.1 A 3-year-old boy with salt disposition on skin
Metabolism is defi ned as the sum total of all the chemical reactions that are taking place in the body. Metabolism is derived from a Greek word, metabellein, which means “to change”. It includes the process by which cells use food mate-rial to obtain energy, store excess calories for future use and build up various substances. Metabolism also includes deg-radation and excretion of unnecessary compounds. In short, metabolism is sum total of all those processes that turn food into fl esh.
Bioenergetics is the fi eld of biochemistry that deals with transformation and utilization of energy in biological systems.
It concerns only with the initial and the fi nal energy states of reaction components, and predicts the energetic feasibility of chemical reaction. However, it provides no information about the mechanism or the rate of reaction. These aspects are measured in kinetics.
In this chapter, general aspects about metabolism and cellular bioenergetics are discussed. After going through this chapter, the student should be able to understand:
Fundamental design of metabolic network; interdependence of metabolic reactions.
Regulation of metabolic pathways and various techniques used to study the details of metabolism.
Principles of bioenergetics: laws of thermodynamics; free energy, entropy and enthalpy; equilibrium constant.
Role of ATP as energy carrier; concept of high-energy and super high-energy compounds and substrate level phos-phorylation; other energy rich nucleoside triphosphates.
M E TA B OL I SM A N D
C E L L B IOE N E R G E T IC S
I. Overview of Metabolism A. General Considerations
Metabolism serves two important purposes:
1. To release energy from the ingested food material through catabolic degradation, and to convert this energy into a form that can be used for cellular work.
2. To transform small organic compounds into macro-molecules. This aspect of metabolism also includes transformation of one group of organic compounds into another.
During catabolic degradation, the energy inherent in the organic molecules (particularly carbohydrates and
8
lipids) is released. It is then trapped and stored as ade-nosine triphosphate (ATP). The stored energy can be released from ATP when needed and used to perform cellular work (Fig. 8.1). The major cellular works are:
Transport of organic molecules and inorganic ions across the cell membrane.
Mechanical work, such as muscle contraction.
Electrical work (e.g. nerve conduction).
Ensure fi delity of information transfer.
The second major purpose of metabolism is to syn-thesize a vast array of macromolecules, which include carbohydrates, proteins, lipids and nucleic acids. It is amazing that so many diverse biomolecules are intracel-lularly synthesized from a limited number of organic compounds. Evidently, thousands of reactions are
intracellularly. It is noteworthy that these conversions occur in mild conditions of temperature and pH that prevail within the cell.
An important example that illustrates this design is the sequence of reactions that converts glucose to pyru-vate (i.e. glycolytic sequence). As soon as the glucose enters the cell, a phosphate group from ATP is added to it to form glucose 6-phosphate. Glucose 6-phosphate becomes the substrate for the next reaction, in which an isomerase converts it into fructose 6-phosphate. The latter then serves as substrate for another enzyme-catalyzed reaction, and the sequence continues through six more reactions until glucose is converted to pyruvate. The reac-tions of this metabolic pathway are summarized in Figure 8.2.
The energy inherent in the substrate glucose is released in small packets in a stepwise fashion and is effectively captured.
If the glucose to pyruvate conversion occurred in a single step, the energy inherent in the glucose molecule could not have been trapped as ATP so effectively. A stepwise transformation ensures effi cient and effective trapping of the energy. Further, some of the intermediates of this pathway are channeled into other pathways; for example, glucose 6-phosphate can enter glycogenesis or the pen-tose phosphate pathway, and 1,3-bisphosphoglycerate can form 2,3-bisphosphoglycerate.
Metabolic pathway appears like an intricate and inte-grated web of chemical reactions wherein the individ-ual threads are interconnected at several points. In subsequent chapters, individual metabolic pathways would be discussed separately with an aim to simplify and categorize. This might give an erroneous impression that each pathway is self-contained and isolated.
involved in the processes which split, join and rearrange the atoms of organic compounds, thus resulting in gen-eration of complex biomolecules. Each of these reactions are catalyzed by a specifi c enzyme.
Metabolism comprises a highly integrated network of chemical reactions, which can be subdivided into catab-olism and anabcatab-olism. Catabolic reactions are used to extract energy from fuels, and anabolism comprises reactions that use this energy for biosynthesis.
A bird’s eye view of the scheme of metabolism is pre-sented in this chapter with a focus on fundamental prin-ciples underlying metabolism in the cell. The details of reactions of individual metabolic pathways are given in subsequent chapters.