Phospholipids are cleaved by different phospholipases. Phospholipase A2 cleaves the central fatty acid at C2 of glycerol residues. The resulting lysophospholipid can lyse cell membranes; interestingly, many snake venoms contain high dosages of phospholipase A2. Phospholipase A1 hydrolyzes the fatty acid at C1 of glycerol, while phospholipase C opens the phosphate ester bonds with glycerol.
A pharmacologically important lipid class, the eicosanoids, is only mentioned briefly here. To summarize, this class includes prostaglandins, thromboxanes, and leukotrienes. These play many roles and act as paracrine mediators (e.g. in pain, fever, inflammation, blood pressure, and blood coagulation). Phospholipase A2 releases arachidonic acid from phosphatidylcholine, which contains the fourfold unsaturated arachidonic acid in its C2 position. Arachidonic acid is converted into prostaglandin (e.g. example by cyclooxygenase). This enzyme is an important target for many drugs (the so‐called nonsteroidal anti‐inflammatory drugs [NSAIDs]), among which aspirin (acetylsalicylic acid) is the most famous. Inflammation can also be effectively suppressed by inhibiting the expression of phospholipase A2 by corticoids (e.g. cortisone medications).
Triacylglycerides, not phospholipids, are present in the storage tissue of plants and animals. These are broken down by lipases.
The steroid cholesterol (Figure 2.5) is an important and common building block of animal membranes (it is missing in the membranes of bacteria, fungi, and plants). It is stored in the membrane, parallel to the phospholipids (Figure 2.2), with its polar hydroxyl group oriented toward the cell exterior. Cholesterol is a stiff molecule that stabilizes biological membranes and lowers their fluidity and permeability. In biological membranes, local assemblies of membrane proteins usually rich in cholesterol, known as rafts, have been found. Cholesterol is transported as cholesteryl ester, such as cholesterol‐3‐stearate in lipoproteins (see Chapter 5.4).
Figure 2.5 Cholesterol and related sterols. Cholesterol; β‐sitosterol replaces cholesterol in plants; ergosterol is present in the membranes of fungi; testosterone; β‐estradiol; cortisol; aldosterone; active vitamin D.
Cholesterol can be synthesized in the body; the biggest portion, however, is obtained from food. It is important not only to build up membranes but also as a precursor for the synthesis of important hormones and vitamins (Figure 2.5):
Glucocorticoids. For example, cortisol (from the adrenal gland) influences the metabolism of carbohydrates, proteins, and lipids; cortisol inhibits phospholipase A2, induces several genes such as the transcription factor NF‐κB, and thus suppresses inflammation processes.
Mineralocorticoids. For example, aldosterone (from the adrenal gland) regulates the secretion of salt and water through the kidneys.
Sexual hormones. Androgens (testosterone, formed in the testicles) and estrogens (β‐estradiol, formed in the ovaries) are important male and female sexual hormones. They bind intracellular receptors that, as transcription factors, control the expression of sex‐dependent genes (see Section 4.2).
Vitamin D. Vitamin D increases the calcium concentration in the blood and assists in the formation of bones and teeth. Vitamin D deficiency is known as rickets in children and osteomalacia in adults.
2.3 Structure and Function of Proteins
Proteins represent the most important tools of the cell (Table 2.2). They catalyze chemical reactions, transport metabolites through membranes, recognize other molecules, and can regulate gene activity. If we consider genes as the legislative branch, proteins then function as the executive branch (i.e. as the executing organs). Proteins are built according to the same principles in both prokaryotes and eukaryotes.
Twenty amino acids serve as building blocks for peptides and proteins, linked to one another by peptide bonds (Figure 2.6). Polypeptides, therefore, are polymers made from amino acids. Polypeptides are polar molecules, possessing a NH2 group (amino‐ or N‐terminal) on one end and a COOH group (carboxyl‐ or C‐terminal) on the other. The diverse tasks and functions of proteins result from different arrangements (sequences) of amino acids.
Figure 2.6 General structure of amino acids and peptides.
The 20 amino acids differ in their side chains (Figure 2.7). The functional groups of the side chains, which protrude from the α‐C atom, dictate the conformation and later functionality of the protein by molecular recognition or biocatalysis. Amino acids exist in two optical isomers: the D‐ and L‐forms. Polypeptides are composed exclusively of L‐amino acids. D‐Amino acids can be found in bacterial cell walls and in many antibiotics (gramicidin, valinomycin). Since proteases can only cleave peptides composed of L‐amino acids, the incorporation of D‐amino acids results in a certain protection from untimely degradation.
Figure 2.7 Structures of proteinogenic amino acids. (Cysteine muss zu den amino acids with apolar residues.)
The proteinogenic amino acids can be divided into different groups according to their functional groups and residues (Figure 2.7 and Table 2.4):
Amino acids with apolar, lipophilic residues.
Amino acids with polar but uncharged residues (i.e. with hydroxyl or amide groups).
Amino acids with acid groups that are negatively charged.
Amino acids with basic groups that are positively charged.
Table 2.4 Compilation and grouping of the proteinogenic amino acids: two types of abbreviations are recognized internationally, which either consist of one or three letters; the codons that represent the amino acids in the genetic code are also given.
| Classification | Symbols | Codons |
|---|---|---|
|
Neutral and nonpolar amino acids
| ||