Lecture 1 Summary

Membranes and bioenergetics

Biological membranes are certainly the sine qua non of cellular biology. The fundamental importance of membranes is evident from a biochemical perspective. In examining oxidative phosphorylation, we will see in detail how the properties of membranes and the functioning of membrane proteins are absolutely central to the process of converting the reducing power derived from catabolism to the chemical potential energy of ATP.

Composition and structure of membranes

The molecules that make up biological membranes are called lipids, a class of biomolecules that are water-insoluble. Membrane lipids are amphipathic due to the presence of polar and charged groups connected to long hydrocarbon chains of fatty acids. Two examples of fatty acids are palmitate, a saturated, 16-carbon fatty acid, and oleate, an unsaturated fatty acid with 18 carbons. The fatty acids are usually esterified with the hydroxyl group of an alcohol such as glycerol. The most abundant class of membrane lipids are phospholipids.

Phospholipids contain two fatty acids in ester linkages with glycerol, and the third hydroxyl group of glycerol is esterified with phosphate. This grouping is called phosphatidate (phosphatidic acid, or diacylglycerol 3-phosphate), and it is the simplest of the group of phospholipids called phosphoglycerides. In phosphoglycerides derived from phosphatidate, the phosphate is involved in a second ester linkage with another alcohol, such as in phosphatidylcholine (also known as lecithin), in which phosphatidate is linked to choline, a nitrogen-containing alcohol.

The participation of membranes in passive or active transport of specific molecules depends on the functions of membrane proteins. These proteins can act as selective filters, specific transporters, and signal transducers. The difference in location between integral and peripheral membrane proteins is reflected in their dissociablity from the membrane. Oxidative phosphorylation depends upon the function of integral membrane protein complexes that couple the energetically favorable transfer of electrons in a series of redox reactions into the energy of an electrochemical gradient. Specialized membrane proteins of mitochondria perform this coupling.

The impermeability of a membrane (in this case the inner membrane of a mitochondrion) to ions allows integral membrane proteins to pump out hydrogen ions, building up a difference in pH across the membrane. This also makes the inside negatively charged relative to the outside. A different integral membrane protein is able to couple the energetically favorable movement of H⁺ back across the membrane to synthesis of ATP. In the first part of the semester, we will be largely concerned with the details of this process.

Mitochondria

An adequate understanding of the bioenergetics of eukaryotic cells requires a basic knowledge of mitochondrial physiology. (See, for example, Figure 18.3 on p.492 of BTS, which illustrates schematically the gross structural organization of a mitochondrion.) The permeable outer membrane surrounds a highly invaginated inner membrane. The folds of the inner membrane are termed cristae. Between the two membranes lies the intermembrane space.

The compartment enclosed by the inner mitochondrial membrane - the matrix - is a viscous soup of soluble enzymes and metabolites, including the PDH complex and all but one of the enzymes of the citric acid cycle. The protein complexes of oxidative phosphorylation are located in the inner mitochondrial membrane. Many other inner mitochondrial membrane proteins are responsible for the transport of key metabolites that are exchanged between the cytosol and mitochondrial matrix. Of particular note presently is the fact that NAD⁺ and NADH do not cross the inner mitochondrial membrane, either by passive diffusion across the phospholipid bilayer, or by specific protein-mediated transport. This means that the cytosol and mitochondrial matrix have separate pools of nicotinamide cofactors. However, of the 10 NADH generated in the complete oxidation of glucose, 2 are created in the cytosol. If the reducing equivalents represented by cytosolic NADH are to lead to ATP generation, they must somehow be made available to the electron transport chain. The glycerol phosphate shuttle and the malate-aspartate shuttle are two mechanisms that accomplish this.

Study questions

• Name the major lipid components of biological membranes.
• Draw structures for a typical phospholipid and a typical triacylglycerol.
• Describe the structure of mitochondria.

Page updated 12-27-06

References

1. Berg, Tymoczko, and Stryer. Biochemistry (BTS): 6th edition (2007, Freeman) Ch.12, pp.326-335; Ch.18, pp.502-505.