És - gondolnád-e ? - az élet-elemek között az 5. helyen: a foszfor !

Protein Phosphorylation and Dephosphorylation Are Central to Cellular Control

One common denominator in signal transductions—whether they involve adenylate cyclase, a transmembrane receptor-tyrosine kinase, phospholipase C, or an ion channel—is the eventual regulation of the activity of a protein kinase. We have seen examples of kinases activated by cAMP, insulin, Ca²⁺/calmodulin, Ca²⁺/diacylglycerol, and by phosphorylation catalyzed by another protein kinase. The number of known protein kinases has grown remarkably since their discovery by Edwin G. Krebs and Edmond H. Fischer in 1959. Hundreds of different protein kinases, each with its own specific activator and its own specific protein target(s), may be present in eukaryotic cells. Although many other types of covalent modifications are known to occur on proteins, it is clear that phosphorylations make up the vast majority of known regulatory modifications of proteins.
The addition of a phosphate group to a Ser, Thr, or Tyr residue introduces a bulky, highly charged group into a region that was only moderately polar. When the modified side chain is located in a region of the protein critical to its three-dimensional structure, phosphorylation can be expected to have dramatic effects on protein conformation and thus on the catalytic activity of the protein. As a result of evolution, the kinase-phosphorylated Ser, Thr, and/or Tyr residues of regulated proteins occur within common structural motifs (consensus sequences) that are recognized by their specific protein kinases (Table 22-9).

Lehninger-Nelson-Cox: Principles of Biochemistry, 777.o.

De, ha a vírus belénk oltja a programhibát - abból lesz: a rák !

Many viral oncogenes encode unregulated tyrosine kinase activities, and in some cases the oncogene product is nearly identical to a normal animal-cell receptor, but with the normal signal-binding site defective or missing. For example, the erbB oncogene product, a protein called ErbB, is essentially identical to the normal receptor for epidermal growth factor, except that ErbB lacks the domain that normally binds EGF (Fig. 22-37, p. 777). The erbB2 oncogene is commonly associated with adenocarcinomas (cancers) of the breast, stomach, and ovary.

Lehninger-Nelson-Cox: Principles of Biochemistry, 776.o.

És, micsoda jelerősítés: 1 adrenalin-jelből 10 000 szőlőcukor-molekula !

Lehninger-Nelson-Cox: Principles of Biochemistry, 762.o.

És, az üzenetküldögetés: idegek és mirigyek - és ez a kettő = egy !

... Except for this anatomical difference, the chemical signaling in the neural and endocrine systems is remarkably similar in mechanism. Even some of the chemical messengers are common to both systems. Epinephrine and norepinephrine, for example, serve as neurotransmitters in certain synapses of the brain and smooth muscle and also as hormones regulating fuel metabolism in the liver and in muscle. Although the neural and endocrine systems were traditionally treated as separate entities, it has become clear that in the regulation of metabolism they merge into a single neuroendocrine system.

Lehninger-Nelson-Cox: Principles of Biochemistry, 746.o.

És, azért hogy semmiből se legyen több, mint amennyi kell belőle: a vese !

The ions and low molecular weight solutes in the blood plasma are not fixed components, but are in constant flux between blood and various tissues. Dietary uptake of inorganic ions is, in general, counterbalanced by their excretion in the urine. For many of the components of blood, something near a dynamic steady state is achieved; the concentration of the component changes little, although a continual flux occurs from the digestive tract, through the blood, and to the urine. For example, almost regardless of the dietary intake of Na+, K+, and Ca²⁺, the plasma levels of these ions remain close to 140, 5, and 2.5 mM, respectively. Any significant departure from these values can result in serious illness or death. The kidneys play an especially important role in maintaining the ion balance, serving as a selective filter that allows waste products and excess ions to pass from the blood to the urine while preventing the loss of essential nutrients and ions.

Lehninger-Nelson-Cox: Principles of Biochemistry, 745.o.

És a vér, a csoda: elszállít mindent (anyagot és információt) mindenhonnan, mindenhova !

The blood flows through and connects all of the tissues, mediating the metabolic interactions among them. It transports nutrients from the small intestine to the liver, and from the liver and adipose tissue to other organs; it also transports waste products from the tissues to the kidneys for excretion. Oxygen moves in the blood from the lungs to the tissues, and CO₂ generated by tissue respiration returns in the blood to the lungs for exhalation. Blood also carries hormonal signals from one tissue to another. In its role as signal carrier, the circulatory system resembles the nervous system; both serve to regulate and integrate the activities of different organs.
The average adult human has 5 to 6 L of blood. Almost half of this volume is occupied by three types of blood cells (Fig. 22-9): erythrocytes (red cells), filled with hemoglobin and specialized for carrying O₂ and CO₂; much smaller numbers of leukocytes (white cells) of several types, central to the immune system that defends against infections; and platelets, which help to mediate the blood clotting that prevents loss of blood after injury. The liquid portion is the blood plasma, which is 90% water and 10% solutes. The plasma is very complex in chemical composition; in it are dissolved or suspended a large variety of proteins, lipoproteins, nutrients, metabolites, waste products, inorganic ions, and hormones. Over 70% of the plasma solids are plasma proteins (Fig. 22-9). Major plasma proteins include immunoglobulins (circulating antibodies), serum albumin, apolipoproteins involved in the transport of lipids (as VLDL, LDL, HDL), transferrin (for iron transport), and blood-clotting proteins such as fibrinogen and prothrombin.

Lehninger-Nelson-Cox: Principles of Biochemistry, 744.o.

Az agynak: (szőlő)cukrot és oxigént, bármi áron !

The metabolism of the brain is remarkable in several respects. First, the brain of adult mammals normally uses only glucose as fuel (Fig. 22-8). Second, the brain has a very active respiratory metabolism; it uses almost 20% of the total O₂ consumed by a resting human adult. The use of O₂ by the brain is fairly constant in rate and does not change significantly during active thought or sleep. Because the brain contains very little glycogen, it is continuously dependent on incoming glucose from the blood. If the blood glucose should fall significantly below a certain critical level for even a short period of time, severe and sometimes irreversible changes in brain function may occur.
Although the brain cannot directly use free fatty acids or lipids from the blood as fuels, it can, when necessary, use D-β-hydroxybutyrate (a ketone body) formed from fatty acids in hepatocytes. The capacity of the brain to oxidize β-hydroxybutyrate via acetyl-CoA becomes important during prolonged fasting or starvation, after essentially all the liver glycogen has been depleted, because it allows the brain to use body fat as a source of energy. The use of β-hydroxybutyrate by the brain during severe starvation also spares muscle proteins, which become the ultimate source of glucose for the brain (via gluconeogenesis) during severe starvation.
...
The concentration of glucose dissolved in the plasma is also subject to tight regulation. We have noted the requirement of the brain for glucose and the role of the liver in maintaining the glucose concentration near the normal level of 80 mg/100 mL of blood (about 4.5 mM). When blood glucose in a human drops to half this value (the hypoglycemic condition), the person experiences discomfort and mental confusion (Fig. 22-10); further reductions lead to coma, convulsions, and in extreme hypoglycemia, death. Maintaining the normal concentration of glucose in the blood is therefore a very high priority of the organism, and a variety of regulatory mechanisms have evolved to achieve that end. Among the most important regulators of blood glucose are the hormones insulin, glucagon, and epinephrine. 

Lehninger-Nelson-Cox: Principles of Biochemistry, 744.o.