Final answer:
Membrane proteins are categorized as integral or peripheral, with integral spanning the membrane and peripheral localized to one side. The orientation of these proteins is specific and critical for function; flip-flopping is energetically unfavorable and rare because it disrupts their function.
Step-by-step explanation:
Membrane proteins are integral to the functioning of the cell membrane. The integral proteins usually span the membrane with different parts exposed to the intracellular and extracellular environments. The part of a transmembrane protein that is inside the cell usually has different amino acids and domains compared to the segment exposed to the outside of the cell. Typically, the N-terminus of an integral membrane protein is exposed to the outside of the cell, and the C-terminus to the inside, dictated by how the protein inserts into the membrane during synthesis.
In contrast, peripheral proteins are found only on one side of the membrane and do not span the lipid bilayer but are attached to either integral proteins or lipid molecules. They mainly associate with the membrane through electrostatic and hydrogen bonding and can be on the cytoplasmic side or the extracellular side depending on where they were synthesized and how they are attached to the membrane.
If a membrane protein were to flip-flop, shifting from the outer to the inner surface or vice versa, it would disrupt the specific functions of cell signaling, transport, cell recognition, and enzymatic activity that are dependent on the proteins being in the correct orientation. However, flip-flop of membrane proteins is an extremely rare event because it requires the polar and often charged regions of the protein to pass through the hydrophobic core of the lipid bilayer, which is energetically unfavorable.