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Membrane Proteins and Ion Channels Explained

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Membrane Proteins and Ion Channels Explained

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Riddles and Problems

1. Riddle: Why are cell membranes needed? termed ligand-gated channels, and the ligands that influence
Ans: They are needed to hold together the contents of the them are often chemical messengers (e.g., hormones). (2)
cell. Perhaps the formation of an oily membrane was among Changes in membrane potential can cause the movement of
the first developments of biological evolution millions of the charged regions on a channel protein, altering its shape;
years ago. It is postulated that a membrane barrier with such channels are called voltage-gated channels.
relative impermeability was needed to enclose self-replicating
[Link]: How does an Na+–K+ pump operate in the
molecules of the primitive cell. Biomolecules such as proteins,
membranes?
nucleic acids, sugars and fats are safely enclosed within the
Ans: Initially, the transporter with an associated molecule
cell because of the membrane. Hence, the occurrence of a
of ATP, binds three sodium ions at high affinity sites on the
membrane is considered to be an essential prerequisite for the
intracellular surface of the protein. Two binding sites also
very existence of life.
exist for K+, but at this stage they are in a low affinity state
[Link]: What are the different lipids that occur in and thus do not bind to intracellular K+.
membranes? Why are there many different types of lipids Binding of Na+ results in the activation of an inherent
and proteins in biological membranes? ATPase activity of the transporter protein, causing
Ans: The reason for this is not clearly known. Membranes phosphorylation of the cytosolic surface of the transporter
contain different glycerophospholipids, glycolipids and by ATP and the release of a molecule of ADP. Phosphorylation
cholesterol. Different cells have different lipid compositions. results in a conformational change of the transporter,
The lipid composition of plasma membrane and the membranes exposing the bound sodium ions to the extracellular fluid and
of organelles are different. Even within a single membrane, at the same time reducing the affinity of the binding sites
the composition of the outer and inner halves of the lipid for sodium. The sodium ions are released from their binding
bilayer varies. sites.
The choline component of lecithin has a positive charge, The new conformation of the transporter results in an
the serine of phosphatidylserine exists as a zwitter ion and increased affinity of the two binding sites, allowing two
the carbohydrate of a cerebroside has no charge. Glycolipids molecules of K+ to bind the transporter on the extracellular
such as cerebrosides and gangliosides are common in brain surface. The binding of K+ results in dephosphorylation of
cell membranes, and sphingomyelin is mostly concentrated in the transporter. This returns the transporter to its original
the myelin sheath. Cardiolipin occurs in high concentrations conformation, resulting in reduced affinity of the K+ binding
in the inner mitochondrial membrane of all cells. Phosphatidyl sites and increased affinity of the Na+ binding sites. K+ is
inositol serves as a source of second messengers that carry therefore released from the binding sites of the transporter on
chemical signals in the cells. All these lipids occurring in the intracellular surface (see Chapter 14; Fig. 14.2).
membrane bilayers are not linked by any type of bonds and
Riddle: State briefly the diseases associated with the
5.
hence they move around freely within the membrane structure
abnormalities of membrane proteins.
and each molecule can cover the length of the cell membrane
rapidly. Ans: As we have seen, most of the proteins present in the
membranes are glycoproteins which serve as receptors,
Apart from lipids, the other major component of
channels, transporters, enzymes and structural components.
membranes are proteins. There are several types of proteins
Any abnormality in them results in diseases. Some common
with different characteristics and different functions. These
examples are mentioned here briefly. They are discussed in
different types of proteins need different lipid components
detail in the corresponding chapters.
for proper alignment. Interactions between membrane lipids
and proteins are vital for the regulation of various activities of Cystic fibrosis occurs due to mutations in gene coding for
cells. the CFTR protein involved in chlorine ion transport (details
in Chapter 28). Familial hypercholesterolemia occurs due
[Link]: How do ion channels function in membranes? to mutations in LDL receptor gene (Chapter 20). Wilson
Ans: Ion channels can exist in the open or closed state. disease occurs due to mutation in the gene encoding copper
Changes in membrane permeability to ions occur rapidly when ion dependent ATPase (Chapter 26). Achondroplasia results
these channels open or close. The process of opening and due to mutation of fibroblast growth factor receptor gene.
closing ion channels is known as channel gating. Hereditary spherocytosis occurs due to mutation of spectrin
A single ion channel may open and close many times gene. Paroxysmal nocturnal hemoglobinuria occurs due to
each second, suggesting that the channel protein fluctuates the mutation resulting in defective enzyme catalyzing the
between two conformations. Over an extended period of time, formation of glucosyl phospatidyl-inositol. Hartnup disease
at any given electrochemical gradient, the total number of is due to defective transportation of neutral amino acids in
ions that pass through a channel depends on how often the the intestine and kidneys (Chapters 14 and 22). Cystinuria
channel opens and how long it stays open. is due to defective renal absorption of amino acids cystine,
Two factors can alter the channel protein conformations, ornithine, arginine and lysine (COAL), resulting in kidney
producing changes in the opening frequency or duration. (1) stones (Chapters 22). Leber hereditary optic neuropathy is
The binding of specific molecules to channel proteins may due to mutations in genes of mitochondrial membrane proteins
directly or indirectly produce either an allosteric or covalent (Chapter 16).
change in the shape of the gated channels. Such channels are

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