Question

1. Describe the fluid mosaic model of the plasma membrane. Discuss the role of the membrane in the movement of materials through it by each of the following processes.
   1. Active transport
   2. Passive transport

2. Describe negative and positive feedback loops, and discuss how feedback mechanisms regulate each of the following.
   1. The menstrual cycle in a nonpregnant human female.
   2. Blood glucose levels in humans.

3. Discuss the adaptations that have enabled flowering plants to overcome the following problems associated with life on land.
   1. The absence of an aquatic environment for reproduction
   2. The absence of an aquatic environment to support the plant body
   3. Dehydration of the plant

Answer 1

The lipid bilayer was originally proposed by Davson and Danielle in 1935. Later, the structure of the biomembranes was described as a fluid mosaic model (Singer and Nicolson, 1972).
A. The phospholipids are arranged in bilayers with the polar head groups oriented towards the extracellular side and the cytoplasmic side with a hydrophobic core. The distribution of the phospholipids is such that choline containing phospholipids are mainly in the external layer and ethanolamine and serine containing phospholipids in the inner layer.
B. Each leaflet is 25 Å thick, with the head portion 10 Å and tail 15 Å thick. The total thickness is about 50 to 80 Å.
C. The lipid bilayer shows free lateral movement of its components, hence the membrane is said to be fluid in nature. Fluidity enables the membrane to perform endocytosis and exocytosis.

D. However, the components do not freely move from inner to outer layer, or outer to inner layer (flip-flop movement is restricted). During apoptosis (programed cell death), flip flop movement occurs.
This flip-flop movement is catalyzed by enzymes. Flippases
catalyze the transfer of amino phospholipids across the membrane. Floppases catalyze the outward directed movement, which is ATP dependent. This is mainly seen in the role of ABC proteins mediating the efflux of cholesterol and the extrusion of drugs from cells. The MDR associated p-glycoprotein is a floppase.
E. The cholesterol content of the membrane alters the fluidity of the membrane. When cholesterol concentra­tion increases, the membrane becomes less fluid on the outer surface, but more fluid in the hydrophobic core. The effect of cholesterol on membrane fluidity is different at different temperatures. At temperature below the Tm, cholesterol increases fluidity and there-by permeability. At temperatures above the Tm, cholesterol decreases fluidity.
F. The nature of the fatty acids also affects the fluidity of
the membrane, the more unsaturated cis fatty acids increase the fluidity.
The fluidity of the membrane is maintained by the length of
the hydrocarbon chain, degree of unsaturation and nature of the polar head groups. Trans fatty acids (TFA) decrease the fluidity of membranes due to close packing of hydrocarbon chains. Cis double bonds create a kink in the hydrocarbon chain and have a marked effect on fluidity. Second OH group of glycerol in membrane phospholipids is often esterified to an unsaturated fatty acid, monounsaturated oleic or polyunsaturated linoleic, linolenic or arachidonic.

Membrane Proteins
A. The peripheral proteins exist on the surfaces of the
bilayer. They are attached by ionic and polar bonds to polar heads of the lipids.
B. Anchoring of proteins to lipid bilayers: Several peripheral
membrane proteins are tethered to the membranes by covalent linkage with the membrane lipids. Since the lipids are inserted into the hydrophobic core, the proteins are firmly anchored. A typical form of linkage is the one involving phosphatidyl inositol which is attached to a glycan.

C. Microdomains on membranes: GPI anchored proteins are often attached to the external surface of plasma membrane at microdomains called lipid rafts. They are areas on the membrane having predominantly glycosphingolipids and cholesterol.

D. The integral membrane proteins are deeply embedded in the bilayer and are attached by hydrophobic bonds or van der Waals forces.
E. Some of the integral membrane proteins span the whole bilayer and they are called transmembrane proteins. The hydrophobic side chains of the amino acids are embedded in the hydrophobic central core of the membrane. The transmembrane proteins can serve as receptors (for hormones, growth factors, neurotransmitters), tissue specific antigens, ion channels, membrane-based enzymes, etc.

Passive Transport
A. Simple Diffusion

Solutes and gases enter into the cells passively. They are driven by the concentration gradient. The rate of entry is proportional to the solubility of that solute in the hydrophobic core of the membrane. Simple diffusion occurs from higher to lower concentration. This does not require any energy. However, it is a very slow process. Diffusion of gases such as O2, CO2, NO and CO
occurs at a rate that is solely dependent upon concentration gradients. Lipophilic molecules will also diffuse across membranes at a rate that is directly proportional to the solubility of the compound in the membrane.
B. Facilitated Diffusion
This is a carrier mediated process. Important features of facilitated diffusion are:
a. The carrier mechanism could be saturated which is similar to the Vmax of enzymes.
b. Structurally similar solutes can competitively inhibit the entry of the solutes.
c. Facilitated diffusion can operate bidirectionally.
d. This mechanism does not require energy but the rate of transport is more rapid than simple diffusion process.
e. The carrier molecules can exist in two conformations, Ping and Pong states. In the pong state, the active sites are exposed to the exterior, when the solutes bind to the specific sites. Then there is a conformational change. In the ping state, the active sites are facing the interior of the cell, where the concentration of the solute is minimal. This will cause the release of the solute molecules and the protein molecule reverts to the pong state.

Active Transport
The salient features of active transport are:
a. This form of transport requires energy. About 40% of the total energy expenditure in a cell is used for the active transport system.
b. The active transport is unidirectional.
c. It requires specialized integral proteins called transporters.
d. The transport system is saturated at higher concentrations of solutes.
e. The transporters are susceptible to inhibition by specific organic or inorganic compounds.