What are the differences between flippase, floppase, and scramblase?

In this quick lesson, we explain the differences between flippase, floppase, and scramblase, important enzymes for lipid transport in the cell membrane and their different dynamic functions in the phospholipid bilayer.

Flippase vs Floppase vs Scramblase

Flippase, floppase, and scramblase are enzymes that change the positions of phospholipids within cell membranes. They are essentially lipid transport proteins that aid the movement of phospholipid molecules within the cell membrane.

What do Flippases do? What do Floppases do?

Flippase moves an outer phospholipid leaflet to the inner phospholipid leaflet. Floppase does the opposite; it moves an inner phospholipid leaflet to the outer phospholipid leaflet.

The outer phospholipid leaflet refers to the phospholipid that is on the side touching the extracellular fluid. The inner phospholipid leaflet is the phospholipid that is on the side touching the cell’s inner cytoplasm.

Only flippase and floppase need ATP or energy to flip or flop the phospholipids inner and outer leaflets.

Easy to Remember Memory Aid: Think of Flippase as a Front Forward Flip. You tuck in to flip forward. Tucking to the inner side.

What do Scramblases do?

Like its name, scramblase scrambles the inner and outer phospholipid leaflets. Scramblase does not need ATP or energy because it flips one outer phopholipid to a inner phospholipid leaflet, and also flips an inner phospholipid leaflet into an outer phospholipid leaflet. Compared to flippase and floppase, scramblase however is calcium dependent (Ca2+ dependent) to function.

Works Cited

1. Hankins, Hannah. NCBI. Role of flippases, scramblases, and transfer proteins. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4275391/
2. Kobayashi, Toshihide. Transbilayer lipid asymmetry. https://www.cell.com/current-biology/comments/S0960-9822(18)30009-5
3. Sharom, Frances. Flipping and flopping – Lipids on the move. https://iubmb.onlinelibrary.wiley.com/doi/pdf/10.1002/iub.515

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