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.

Zsírszövet: a gyorsreagálású energiatároló !

Adipose tissue, which consists of adipocytes (fat cells) (Fig. 22-4), is amorphous and widely distributed in the body: under the skin, around the deep blood vessels, and in the abdominal cavity. It typically makes up about 15% of the mass of a young adult human, with approximately 65% of this mass being in the form of triacylglycerols. Adipocytes are metabolically very active, responding quickly to hormonal stimuli in a metabolic interplay with the liver, skeletal muscles, and the heart.

Lehninger-Nelson-Cox: Principles of Biochemistry, 741.o.

Többet ésszel, mint erővel: amikor az izom táplálja az agyat !

But in the period between meals, especially if prolonged, there is some degradation of muscle protein to amino acids ⑤. These amino acids donate their amino groups (by transamination) to pyruvate, the product of glycolysis, to yield alanine, which is transported to the liver and deaminated. The resulting pyruvate is converted by hepatocytes into blood glucose (via gluconeogenesis), and the NH₃ is converted into urea for excretion. The glucose returns to the skeletal muscles to replenish muscle glycogen stores. One benefit of this cyclic process, the glucose-alanine cycle (see Fig. 17-9), is the smoothing out of fluctuations in blood glucose in the periods between meals. The amino acid deficit incurred in the muscles is made up after the next meal from incoming dietary amino acids.

Lehninger-Nelson-Cox: Principles of Biochemistry, 740.o.

Szervezetünk CPU-ja: a máj !

Each tissue and organ of the human body has a specialized function that is reflected in its anatomy and its metabolic activity. Skeletal muscle, for example, uses metabolic energy to produce motion; adipose tissue stores and releases fats, which serve as fuel throughout the body; the brain pumps ions to produce electrical signals. The liver plays a central processing and distributing role in metabolism and furnishes all the other organs and tissues with a proper mix of nutrients via the bloodstream. The functional centrality of the liver is indicated by the common reference to all other tissues and organs as "extrahepatic" or "peripheral." We therefore begin our discussion of the division of metabolic labor by considering the transformations of carbohydrates, amino acids, and fats in the mammalian liver. This is followed by brief descriptions of the major metabolic functions of adipose tissue, muscle, the brain, and the tissue that interconnects all others: the blood.

Lehninger-Nelson-Cox: Principles of Biochemistry, 736.o.

A rák gyógyításához is közelebb visz, ha megértjük az enzimek működését

És, az öregedés gyógyításához is !

Cancer cells grow more rapidly than the cells of most normal tissues, and thus they have greater requirements for nucleotides as precursors to DNA and RNA synthesis. Consequently, cancer cells are generally more sensitive to inhibitors of nucleotide biosynthesis than are normal cells. A growing array of important chemotherapeutic agents act by inhibiting one or more enzymes in these pathways. We will examine several well-studied examples that both illustrate productive approaches to treatment of cancer and facilitate an understanding of how these enzymes work.

Lehninger-Nelson-Cox: Principles of Biochemistry, 730.o.

Zseniális: így gyógyítják a köszvényt

Az öregedést is hasonló zsenialitással kell gyógyítani !

The precise cause of gout is not known, but it is suspected to be due to a genetic deficiency of one or another enzyme concerned in purine metabolism.
Gout can be effectively treated by a combination of nutritional and drug therapies. Foods especially rich in nucleotides and nucleic acids, such as liver or glandular products, are withheld from the diet. In addition, major improvement follows use of the drug allopurinol (Fig. 21-40), an inhibitor of xanthine oxidase, the enzyme responsible for converting purines into uric acid. When xanthine oxidase is inhibited, the excreted products of purine metabolism are xanthine and hypoxanthine, which are more soluble in water than uric acid and less likely to form crystalline deposits. Allopurinol was developed by Gertrude Elion and George Hitchings, who also developed acyclovir, used to treat AIDS, and other purine analogs used in cancer chemotherapy.

Lehninger-Nelson-Cox: Principles of Biochemistry, 730.o.