Angiotensin I

Angiotensin I is an N-terminal decapeptide which is formed when renin acts on angiotensinogen. Angiotensin I is the precursor of angiotensin II. Renin is produced in the kidneys in response to both decreased intra-renal blood pressure at the juxtaglomerular cells, or decreased delivery of Na+ and Cl- to the macula densa. If more Na+ is sensed, renin release is decreased. Renin cleaves the peptide bond between the leucine (Leu) and valine (Val) residues on angiotensinogen, creating the ten amino acid peptide (des-Asp) angiotensin I (CAS# 9041-90-1). Angiotensin I appears to have no biological activity and exists solely as a precursor to angiotensin II.

Variants of the angiotensin I converting enzyme (peptidyl-dipeptidase A) 1 (ACE1) gene and the apolipoprotein E gene (APOE) have been suggested to be associated with human longevity. The association between the ACE1 insertion (I allele)/deletion (D allele) polymorphism and longevity have been tested in a population from Southern Italy and examined the impact of geographical variation on ACE1 allele frequencies on reported associations from other European countries. ACE1 and APOE genotypes were obtained on 82 centenarians and 252 middle-aged, unrelated subjects or volunteers. No statistically significant differences were found in ACE1 genotype or allele frequencies between centenarians and controls in this Southern Italian population nor was there any observed interaction with APOE alleles that are also reputed to be linked to longevity. However, decreasing gradients in ACE1*I allele frequencies, both in centenarians and controls, with concomitant increases in ACE1*D allele frequencies (particularly the ACE1*D/*D genotype) were observed to be statistically significant from Northern to Southern regions of Europe.

Angiotensinogen

Angiotensinogen is a serum alfa-2-globulin which is secreted in the liver and released into the blood circulation. Angiotensinogen is a member of the serpin family. It is not known whether it inhibits other enzymes, unlike most serpins. On hydrolysis by renin, angiotensinogen gives rise to angiotensin. Plasma angiotensinogen levels are increased by plasma corticosteroid, estrogen, thyroid hormone, and angiotensin II levels.

Also known as renin substrate, angiotensinogen is A 60 kD glycoprotein of the alfa-2-globulin fraction of plasma proteins, which is synthesized and released from the liver. It is cleaved in the circulation to form the biologically inactive, angiotensin I, a decapeptide split from the N-terminal by renin, a proteolytic enzyme.

Human angiotensinogen is 452 amino acids long, but other species have angiotensinogen of varying sizes. The first 12 amino acids are the most important for activity.

Erythropoiesis

Erythropoiesis is the development and production of red blood cells, or erythrocytes, in the bone marrow. Also called hematopoiesis, erythropoiesis is stimulated by the hormone erythropoietin, which is produced in the kidney. In the early fetus, erythropoiesis takes place in the mesodermal cells of the yolk sac.

By the third or fourth month, erythropoiesis moves to the spleen and liver. By the second year, it moves to the bone marrow. In humans with certain diseases and in some animals, erythropoiesis also occurs outside the bone marrow, within the spleen or liver. This is called extramedullary erythropoiesis. By age 25, the tibia and femur cease to be important sites of hematopoiesis, but the vertebrae, sternum, pelvis and ribs, and cranial bones continue to produce red blood cells throughout life.

The organ responsible for the production of erythrocytes (red blood cells) is the kidney. When this organ detects low levels of oxygen in the blood, it responds by releasing a hormone called erythropoietin, which then travels to the red bone marrow to stimulate the marrow to begin production of erythrocytes. Once the erythropoietin has begun stimulating the red bone marrow to start manufacturing red blood cells, a series of events occurs. In the bone marrow there are many special stem cells from which red blood cells can be formed. As these cells mature, they extrude their nucleus as they slowly fill with hemoglobin until they are bright red reticulocytes ready to escape the bone marrow and squeeze into the blood capillaries to begin circulating around the body.

Erythrocytes precursors, called erythroid cells, begin as pluripotential stem cells. The first cell that is recognizable as specifically leading down the red cell pathway is the proerythroblast. As development continues, the nucleus becomes somewhat smaller and the cytoplasm becomes more basophilic, due to the presence of ribosomes. In this stage the cell is called a basophilic erythroblast. The cell will continue to become smaller throughout development. As the cell begins to produce hemoglobin, the cytoplasm attracts both basic and eosin stains, and is called a polychromatophilic erythroblast. The cytoplasm eventually becomes more eosinophilic, and the cell is called an orthochromatic erythroblast. This orthochromatic erythroblast will then extrude its nucleus and enter the circulation as a reticulocyte. Reticulocytes are so named because these cells contain reticular networks of polyribosomes. As reticulocytes loose their polyribosomes they become mature red blood cells.

Peritubular Capillaries

Peritubular capillaries are a network of capillaries (tiny blood vessels) which surround the renal tubules of the nephrons, allowing reabsorption and secretion between blood and the inner lumen of the nephron.

Ions and minerals that need to be saved in the body are reabsorbed into the peritubular capillaries through active transport, secondary active transport, or transcytosis. The ions that need to be excreted as waste are secreted from the capillaries into the nephron to be sent towards the bladder and out of the body. The majority of exchange through the peritubular capillaries takes place because of chemical gradients, osmosis and Na+ pumps.

The kidney has two capillary beds arranged in series, the glomerular capillaries which are under high pressure for filtering, and the peritubular capillaries which are situated around the tubule and are at low pressure, allowing large volumes of fluid to be filtered and reabsorbed.

Preservation of Peritubular Capillary Endothelial Integrity

Decreased renal blood flow following an ischemic insult contributes to a reduction in glomerular filtration. However, little is known about the underlying cellular or subcellular mechanisms mediating reduced renal blood flow in human ischemic acute kidney injury (AKI) or acute renal failure (ARF). To examine renal vascular injury following ischemia, intraoperative graft biopsies were performed after reperfusion in 21 cadaveric renal allografts. Confocal fluorescence microscopy was utilized to examine vascular smooth muscle and endothelial cell integrity as well as peritubular interstitial pericytes in the biopsies.

The reperfused, transplanted kidneys exhibited postischemic injury to the renal vasculature, as demonstrated by disorganization/disarray of the actin cytoskeleton in vascular smooth muscle cells and disappearance of von Willebrand factor from vascular endothelial cells. Damage to peritubular capillary endothelial cells was more severe in subjects destined to have sustained ARF than in those with rapid recovery of their graft function. In addition, peritubular pericytes/myofibroblasts were more pronounced in recipients destined to recover than those with sustained ARF. Taken together, these data suggest damage to the renal vasculature occurs after ischemia-reperfusion in human kidneys. Preservation of peritubular capillary endothelial integrity and increasing pericytes may be critical to recovery from postischemic AKI.

Erythropoietin

Erythropoietin is a glycoprotein hormone which promotes red blood cell production, which is called erythropoiesis. Erythropoietin acts on the bone marrow to increase the production of red blood cells. Stimuli such as bleeding or moving to high altitudes, where oxygen is scarcer, trigger the release of erythropoietin (EPO). This hormone is produced by the peritubular capillary endothelial cells of the kidney. Erythropoietin is a cytokine for erythrocyte (red blood cell) precursors in the bone marrow.

Erythropoietin is also called hematopoietin and has other known biological functons; it is involved in the brain's response to neuronal injury, taking part in the wound healing process. When exogenous erythropoietin is used as a performance-enhancing drug, it is classified as an erythropoiesis-stimulating agent (ESA).

Since Erythropoietin increases the hematocrit, which is the proportion of blood volume that is occupied by red blood cells, it enables more oxygen to flow to the skeletal muscles. Some cyclists have used recombinant hematopoietin to enhance their performance. Although recombinant EPO has exactly the same sequence of amino acids as the natural hormone, the sugars attached by the cells used in the pharmaceutical industry differ from those attached by the cells of the human kidney. This difference can be detected by a test of the athlete's urine.

Renin

Renin, or angiotensinogenase, is an enzyme released by the juxtaglomerular cells of the kidney. It takes part in the body's renin-angiotensin system (RAS) that mediates extracellular volume and arterial vasoconstriction. Thus renin regulates the body's mean arterial blood pressure. A test can be done to measure the amount of renin in the blood.

Renin is released when the sodium levels in the body, or blood volume, has decreased. Renin also plays an important role in the release of aldosterone, a hormone that helps control the body's salt and water balance.

The primary structure of renin precursor consists of 406 amino acids with a pre- and a pro- segment carrying 20 and 46 amino acids respectively. Mature renin contains 340 amino acids and has a mass of 37 kDa. Renin circulates in the blood stream and breaks down (hydrolyzes) angiotensinogen secreted from the liver into the peptide angiotensin I.

Tubule Reabsorption

Reabsorption of glucose occurs in proximal convoluted tubule. Here, all that useful glucose, aminoacids, bicarbonate, and water are reabsorbed from the ultra-filtrate and put back into the blood. If the glucose were not absorbed it would end up in your urine. This happens in people who are suffering from diabetes.

Reabsorption of sodium and chloride takes place in the distal convoluted tubule of the nephron. Sodium absorption by the distal tubule is mediated by the hormone aldosterone, which is secreted by the adrenal gland. Aldosterone increases reabsorption of sodium (Na) and water, making the tubule secrete potassium (K+). Sodium and chloride (salt) reabsorption is also mediated by a group of kinases called WNK kinases.

The kidney distant tubule also reabsorbs calcium (Ca2+) in response to parathyroid hormone, taking part in calcium level regulation. PTH effect is mediated through phosphorylation of regulatory proteins and enhancing the synthesis of all transporters within the distal convoluted tubule. In the presence of parathyroid hormone, the distal convoluted tubule reabsorbs more calcium and excretes more phosphate. When aldosterone is present, more sodium is reabsorbed and more potassium excreted.

Angiotensin

Angiotensin is a protein which causes blood vessels to constrict, raising the blood pressure. The angiotensin is part of the renin-angiotensin system, which is a major target for drugs that lower blood pressure. It stimulates the release of aldosterone from the adrenal cortex. Aldosterone promotes sodium retention in the distal nephron, in the kidney, which also drives blood pressure up.

Angiotensin is an oligopeptide in the blood that causes vasoconstriction, increased blood pressure, and release of aldosterone from the adrenal cortex. It is a hormone and a powerful dipsogen. It is derived from the precursor molecule angiotensinogen, a serum globulin produced in the liver. It plays an important role in the renin-angiotensin system. Angiotensin was isolated for the first time as "angiotonin" in Indianapolis, USA, in the late 1930s. It was subsequently characterized and synthesized by groups at the Cleveland Clinic and Ciba laboratories in Basel, Switzerland.

Extraglomerular Mesangial Cells

Extraglomerular mesangial cells are light-staining cells which are located outside the glomerulus, in the kidney, between the macula densa and the afferent arteriole. Also called Lacis cells, they form the juxtaglomerular apparatus in combination with two other types of cells: the macula densa of the distal convoluted tubule and Juxtaglomerular cells of the afferent arteriole. This apparatus controls blood pressure through the Renin-Angiotensin-Aldosterone system. The specific function of Lacis cells is not well understood, but it is believed that it is associated with the secretion of erythropoietin.

It has been hypothesized that fluctuations of the ionic composition in the interstitium of juxtaglomerular apparatus (JGA) modulate the function of extraglomerular mesangial cells (MC), thereby participating in tubuloglomerular feedback (TGF) signal transmission. Scientists have examined the effects of isosmotic reductions in ambient sodium concentration ([Na+]) and [Cl-] on cytosolic calcium concentration ([Ca2+]i) in cultured rat MC. Rapid reduction of [Na+] or [Cl-] in the bath induced a concentration-dependent rise in [Ca2+]i. MC are much more sensitive to decreases in ambient [Cl-] than to [Na+]; a decrease in [Cl-] as small as 14 mM was sufficient to elicit a detectable [Ca2]i response. These observations suggest that MC can be readily stimulated by modest perturbations of extracellular [Cl-]. Next, we examined whether activation of MC by lowered ambient [Cl-] influences cellular nitric oxide (NO) production.

Juxtaglomerular Cells

The juxtaglomerular cells, or Goormaghtigh cells, are cells which synthesize, store, and secrete the enzyme renin. They are located at the vascular pole of the renal corpuscle in the kidney. Forming a component of the juxtaglomerular complex, they are specialized smooth muscle cells in the wall of the afferent arteriole that delivers blood to the glomerulus. In synthesizing renin, they play a critical role in the renin-angiotensin system and thus in renal autoregulation, the self-governance of the kidney.

Juxtaglomerular cells also harbor ß1 adrenergic receptors, similar to cardiac muscle. When stimulated by epinephrine or norepinephrine, these receptors induce the secretion of renin. In appropriately stained slides, juxtaglomerular cells are distinguished by their granulated cytoplasm.

Renin-Angiotensin System

The renin-angiotensin system (RAS) is a hormone system that regulates blood pressure and water balance.

The kidneys produce renin when the blood volume is low. Renin stimulates the production of angiotensin. Angiotensin causes blood vessels to constrict, resulting in increased blood pressure. Angiotensin also stimulates the secretion of the hormone aldosterone from the adrenal cortex. Aldosterone causes the tubules of the kidneys to increase the reabsorption of sodium and water. This increases the volume of fluid in the body, which also increases blood pressure.

The system can be activated when there is a loss of blood volume or a drop in blood pressure (such as in hemorrhage). If the perfusion of the juxtaglomerular apparatus in the kidney's macula densa decreases, then the juxtaglomerular cells release the enzyme renin. Renin cleaves a zymogen, an inactive peptide, called angiotensinogen, converting it into angiotensin I. Angiotensin I is then converted to angiotensin II by angiotensin-converting enzyme (ACE) which is found mainly in lung capillaries. Angiotensin II is the major bioactive product of the renin-angiotensin system, binding to receptors on intraglomerular mesangial cells, causing these cells to contract along with the blood vessels surrounding them and causing the release of aldosterone from the zona glomerulosa in the adrenal cortex. Angiotensin II acts as an endocrine, autocrine/paracrine, and intracrine hormone. Patil Jaspal et al. have shown local synthesis of Angiotensin III in neurons of sympathetic ganglia.

If the renin-angiotensin-aldosterone system is too active, blood pressure will be too high. There are many drugs that interrupt different steps in this system to lower blood pressure. These drugs are one of the main ways to control high blood pressure (hypertension), heart failure, kidney failure, and harmful effects of diabetes.

Basal Metabolic Rate

Basal metabolic rate (BMR), and the resting metabolic rate (RMR), is the amount of energy expended while at rest in a neutrally temperate environment, in the post-absorptive state (meaning that the digestive system is inactive, which requires about twelve hours of fasting in humans). The release of energy in this state is sufficient only for the functioning of the vital organs, such as the heart, lungs, brain and the rest of the nervous system, liver, kidneys, sex organs, muscles and skin. BMR decreases with age and with the loss of lean body mass. Increasing muscle mass increases BMR. Aerobic fitness level, a product of cardiovascular exercise, while previously thought to have effect on BMR, has been shown in the 1990s not to correlate with BMR, when fat-free body mass was adjusted for.

Both basal metabolic rate and resting metabolic rate are usually expressed in terms of daily rates of energy expenditure. The early work of the scientists J. Arthur Harris and Francis G. Benedict showed that approximate values could be derived using body surface area (computed from height and weight), age, and sex, along with the oxygen and carbon dioxide measures taken from calorimetry. Studies also showed that by eliminating the sex differences that occur with the accumulation of adipose tissue by expressing metabolic rate per unit of "fat-free" or lean body weight, the values between sexes for basal metabolism are essentially the same. Exercise physiology textbooks have tables to show the conversion of height and body surface area as they relate to weight and basal metabolic values. The primary organ responsible for regulating metabolism is the hypothalamus. The hypothalamus is located on the brain stem and forms the floor and part of the lateral walls of the third ventricle of the cerebrum.

Metabolism

Metabolism is the set of chemical processes which occur in cells of living organisms to maintain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories: 1) catabolism, which breaks down organic matter to harvest energy in cellular respiration; 2) anabolism, which uses energy to construct components of cells such as proteins and nucleic acids.

Metabolism comprises all the chemical reactions by which molecules taken into an organism are broken down to produce energy and by which energy is used to build up complex molecules. All metabolic reactions fall into one of two general categories: catabolic and anabolic reactions, or the processes of breaking down and building up, respectively. An example of metabolism from daily life takes place in the process of taking in and digesting nutrients.

Catabolism and anabolism share an important common sequence of reactions known collectively as the citric acid cycle, the tricarboxylic acid cycle, or the Krebs cycle. Named after the German biochemist Sir Hans Adolf Krebs (1900-1981). The citric acid cycle is a series of chemical reactions in which tissues use carbohydrates, fats, and proteins to produce energy; it is part of a larger series of enzymatic reactions known as oxidative phosphorylation. In the latter reaction, glucose is broken down to release energy, which is stored in the form of ATP—a catabolic sequence.

The chemical reactions of metabolism are organized into metabolic pathways, in which one chemical is transformed through a series of steps into another chemical, by a sequence of enzymes. Enzymes are crucial to metabolism because they allow organisms to drive desirable reactions that require energy and will not occur by themselves, by coupling them to spontaneous reactions that release energy. As enzymes act as catalysts they allow these reactions to proceed quickly and efficiently. Enzymes also allow the regulation of metabolic pathways in response to changes in the cell's environment or signals from other cells.

Metabolism Explained by Professor (Video)

Cellular Respiration

Cellular respiration is the set of metabolic reactions and processes which occur in cells to convert biochemical energy from nutrients into adenosine triphosphate (ATP), and then release waste products. The type of reactions which take place in respiration are catabolic reactions which consist of the oxidation of one molecule and the reduction of another. In other words, cellular respiration is the process of oxidizing food molecules, like glucose, to carbon dioxide and water. Then the energy released is trapped in the form of ATP for use by all the energy-consuming activities of the cell.

Nutrients commonly used by animal and plant cells in cellular respiration include glucose, amino acids and fatty acids, and a common oxidizing agent (electron acceptor) is molecular oxygen (O2). Bacteria and archaea can also be lithotrophs and these organisms may respire using a broad range of inorganic molecules as electron donors and acceptors, such as sulfur, metal ions, methane or hydrogen. Organisms that use oxygen as a final electron acceptor in respiration are described as aerobic, while those that do not are referred to as anaerobic.

The process of cellular respiration occurs in two phases: 1) glycolysis, the breakdown of glucose to pyruvic acid; 2) the complete oxidation of pyruvic acid to carbon dioxide and water.

Cellular Respiration Animation Video

Chemiosmosis

Chemiosmosis is the process by which ions diffuse across a mitochondrial permeable membrane. More specifically, it relates to the generation of ATP by the movement of hydrogen ions across a membrane during cellular respiration.

In chemiosmosis, ions (electrons) of hydrogen diffuse from an area of high electron concentration to an area of lower electron concentration. An electrochemical concentration gradient of electrons across a membrane could be harnessed to make ATP. This process is similar to osmosis, which is the diffusion of water across a membrane, hence the name chemiosmosis.

ATP synthase is the enzyme that makes ATP by chemiosmosis. It allows electrons to pass through the membrane using the kinetic energy to phosphorylate ADP making ATP. The generation of ATP by chemiosmosis occurs in chloroplasts and mitochondria as well as in some bacteria.

Chemiosmotic phosphorylation is the third pathway that produces ATP from inorganic phosphate and an ADP molecule. This process is part of oxidative phosphorylation. The complete breakdown of glucose in the presence of oxygen is called cellular respiration. The last steps of this process occur in mitochondria. The reduced molecules NADH and FADH2 are generated by the Krebs cycle and glycolysis. These molecules pass electrons to an electron transport chain, which uses the energy released to create a proton gradient across the inner mitochondrial membrane. ATP synthase then uses the energy stored in this gradient to make ATP. This process is called oxidative phosphorylation because oxygen is the final electron acceptor and the energy released by reducing oxygen to water is used to phosphorylate ADP and generate ATP.

Electron Transport Chain (Video)

Catabolism

Catabolism is the set of metabolic pathways which break down molecules into smaller units and release energy. A simpler way to put it: catabolism is the metabolic breakdown of complex molecules into simpler ones, often resulting in a release of energy. In catabolism, large molecules such as polysaccharides, lipids, nucleic acids and proteins are broken down into smaller units such as monosaccharides, fatty acids, nucleotides and amino acids, respectively. As molecules such as polysaccharides, proteins and nucleic acids are made from long chains of these small monomer units.

People who are undernourished are sometimes said to be in a catabolic state, which means that they are catabolizing their body tissues, without replacing them. Hence, a proper relation between anabolism and catabolism is essential for the maintenance of bodily homeostasis and dynamic equilibrium.

The byproducts of catabolism are cellular wastes, which include lactic acid, acetic acid, carbon dioxide, ammonia, creatinine, and urea. The creation of these wastes is usually an oxidation process involving a release of chemical free energy, some of which is lost as heat, but the rest of which is used to drive the synthesis of adenosine triphosphate (ATP). This molecule acts as a way for the cell to transfer the energy released by catabolism to the energy-requiring reactions that make up anabolism.

Schematic diagram of catabolism

Anabolism

Anabolism, or anabolic process, is the set of metabolic pathways which build molecules from smaller units. It is the phase of metabolism in which simple substances are synthesized into the complex materials of living tissue. These reactions require energy. One way of categorizing metabolic processes, whether at the cellular, organ or organism level is as 'anabolic' or as 'catabolic', which is the opposite. Anabolism is powered by catabolism, where large molecules are broken down into smaller parts and then used up in respiration. Many anabolic processes are powered by adenosine triphosphate (ATP).

As anabolism is the metabolic synthesis of proteins, fats, and other constituents of living organisms from molecules or simple precursors, it has a tendency toward building up organs and tissues. These processes produce growth and differentiation of cells and increase in body size, a process that involves synthesis of complex molecules. Examples of anabolic processes include the growth and mineralization of bone and increases in muscle mass.

Endocrinologists have traditionally classified hormones as anabolic or catabolic, depending on which part of metabolism they stimulate. The classic anabolic hormones are the anabolic steroids, which stimulate protein synthesis and muscle growth. The balance between anabolism and catabolism is also regulated by circadian rhythms, with processes such as glucose metabolism fluctuating to match an animal's normal periods of activity throughout the day.

Citric Acid Cycle

The citric acid cycle is a series of enzyme-catalysed chemical reactions, which take place in the matrix of the mitochondrion. The citric acid cycle is very importance in all living cells that use oxygen as part of cellular respiration. The components and reactions of the citric acid cycle were established by seminal work from Albert Szent-Györgyi and Hans Krebs. The citric acid cycle is also called the tricarboxylic acid cycle (TCA cycle), or the Krebs cycle. The Citric Acid Cycle is one of 3 stages of cellular respiration. The other stages are glycolysis and electron transport/oxidative phosphorylation.

The citric acid cycle is part of a metabolic pathway which participates in the chemical conversion of carbohydrates, fats and proteins into carbon dioxide and water to generate a form of usable energy. Other relevant reactions in the pathway include those in glycolysis and pyruvate oxidation before the citric acid cycle, and oxidative phosphorylation after it. In addition, it provides precursors for many compounds including some amino acids and is therefore functional even in cells performing fermentation.

Crystal-Clear Explanation of Citric Acid Cycle / Krebs Cycle (Animation)



The Krebs Cycle Video

Pyruvate Decarboxylation

Pyruvate decarboxylation, also called oxidative decarboxylation, is the biochemical reaction that uses pyruvate to form acetyl-CoA, releasing NADH, a reducing equivalent, and carbon dioxide via decarboxylation. It is also known as the link reaction because it forms an important link between the metabolic pathways of glycolysis and the citric acid cycle. This reaction is usually catalyzed by the pyruvate dehydrogenase complex as part of aerobic respiration. In eukaryotes, pyruvate decarboxylation takes place exclusively inside the mitochondrial matrix; in prokaryotes similar reactions take place in the cytoplasm and at the plasma membrane.

Pyruvate decarboxylation occurs in the mitochondria, unlike the reactions of glycolysis which are cytosolic, and is very common in most organisms as a link to the citric acid cycle. The conversion of pyruvate to acetyl CoA by the pyruvate dehydrogenase complex is a key step in the liver in particular, as it removes any chance of conversion of pyruvate to glucose, or as a transmination substrate. It commits pyruvate to entering the citric acid cycle, where it is either used as a substrate for oxidative phosphorylation, or is converted to citrate for export to the cytosol to serve as a substrate for fatty acid and isoprenoid biosynthesis.

Pyruvate

Pyruvate is the carboxylate (COOH) ion (anion) of pyruvic acid, an organic acid which is a key intersection in several metabolic pathways. It is a chemical substance made in our bodies as a result of glucose metabolism. Pyruvate can be made from glucose through glycolysis and supplies energy to living cells in the citric acid cycle, and can also be converted to carbohydrates via gluconeogenesis, to fatty acids or energy through acetyl-CoA, to the amino acid alanine and to ethanol.

Pyruvate is the end product of glycolysis, which is used and synthesized by many metabolic pathways. In energy generation, it can be either converted to lactate, when the oxygen is not sufficient, or broken down to water and carbon dioxide in the presence of oxygen, generating large amounts of ATP.

Pyruvate, which is a natural metabolic fuel and antioxidant in myocardium and other tissues, exerts a variety of cardioprotective actions when provided at supraphysiological concentrations. Pyruvate increases cardiac contractile performance and myocardial energy state, bolsters endogenous antioxidant systems, and protects myocardium from ischemia-reperfusion injury and oxidant stress.

The Pyruvate Dehydrogenase Complex and Kreb's Cycle explanation ( Video )

Nicotinamide Adenine Dinucleotide

Nicotinamide adenine dinucleotide (NAD) is a coenzyme found in all living cells. Along with the its relative nicotinamide adenine dinucleotide phosphate (NADP), the NAD is one of the most important coenzymes in the cell. The compound is a dinucleotide, since it consists of two nucleotides joined through their phosphate groups, with one nucleotide containing an adenine base and the other containing nicotinamide.

The nicotinamide adenine dinucleotide participates in redox reactions as it brings electrons from one reaction to the next. The coenzyme is therefore found in two forms in cells: NAD is an oxidizing agent, accepting electrons from other molecules and becoming reduced. This reaction forms NADH, which can then be used as a reducing agent to donate electrons. These electron transfer reactions are the main function of NAD. However, it is also used in other cellular processes, notably as a substrate of enzymes that add or remove chemical groups from proteins, in posttranslational modifications. Because of the importance of these functions, the enzymes involved in NAD metabolism are targets for drug discovery.

Because of the positive charge on the nitrogen atom in the nicotinamide ring (upper right), the oxidized forms of these important redox reagents are often depicted as NAD+ and NADP+ respectively. In cells, most oxidations are accomplished by the removal of hydrogen atoms. Both of these coenzymes play crucial roles in this. Each molecule of NAD+ (or NADP+) can acquire two electrons; that is, be reduced by two electrons. However, only one proton accompanies the reduction. The other proton produced as two hydrogen atoms are removed from the molecule being oxidized is liberated into the surrounding medium. For NAD, the reaction is thus: NAD+ + 2H -> NADH + H+

Adenosine Triphosphate

Adenosine triphosphate (ATP) is a molecule used in cells as a coenzyme. Adenosine triphosphate is the immediate source of energy for the mechanical work performed by muscle. ATP is a nucleotide which causes the contraction of the muscle protein actomyosin with the formation of adenosine diphosphate and inorganic phosphate. ATP is also involved in the activation of amino acids, a necessary step in the synthesis of protein. It is often called the "molecular unit of currency" of intracellular energy transfer.

Adenosine triphosphate is the only compound which the body can use directly as fuel for energy-consuming activities, including movement. Without it, we would die. ATP is a high-energy compound made using the energy derived from the breakdown of food during respiration. Physical activity uses enormous quantities of ATP. An active muscle cell requires about two million ATP molecules per second to drive its biochemical machinery.

Adenosine triphosphate transports chemical energy within cells for metabolism. It is produced by photophosphorylation and cellular respiration and used by enzymes and structural proteins in many cellular processes, including biosynthetic reactions, motility, and cell division. One molecule of ATP contains three phosphate groups, and it is produced by ATP synthase from inorganic phosphate and adenosine diphosphate (ADP) or adenosine monophosphate (AMP). Metabolic processes that use ATP as an energy source convert it back into its precursors. ATP is therefore continuously recycled in organisms, with the human body turning over its own weight in ATP each day.

ATP is used as a substrate in signal transduction pathways by kinases that phosphorylate proteins and lipids, as well as by adenylate cyclase, which uses ATP to produce the second messenger molecule cyclic AMP. The ratio between ATP and AMP is used as a way for a cell to sense how much energy is available and control the metabolic pathways that produce and consume ATP. Apart from its roles in energy metabolism and signaling, ATP is also incorporated into nucleic acids by polymerases in the processes of DNA replication and transcription.

Nucleotides

Nucleotides are organic compounds which consists of a nucleoside combined with a phosphate group. Nucleotides are molecules which join together to form the structural units of RNA and DNA. Nucleotides also play important roles in metabolism. In that capacity, they serve as sources of chemical energy (adenosine triphosphate and guanosine triphosphate), participate in cellular signaling (cyclic guanosine monophosphate and cyclic adenosine monophosphate), and are incorporated into important cofactors of enzymatic reactions (coenzyme A, flavin adenine dinucleotide, flavin mononucleotide, and nicotinamide adenine dinucleotide phosphate.

A nucleotide is composed of a nitrogenous base, a five-carbon sugar (either ribose or 2'-deoxyribose), and one to three phosphate groups. Together, the nitrogenous base and sugar comprise a nucleoside. The phosphate groups form bonds with either the 2, 3, or 5-carbon of the sugar, with the 5-carbon site most common. A nucleotide is one of the building blocks of ribonucleic acids (RNA) and deoxyribonucleic acid (DNA). Nucleotides are linked by enzymes in order to make long, chainlike polynucleotides of defined sequence. The order or sequence of the nucleotide units along a polynucleotide chain plays an important role in the storage and transfer of genetic information.

A nucleotide molecule contains three functional groups: a base, a sugar, and a phosphate. It may seem puzzling that a nucleic acid should contain a base. While the base portion does have weakly basic properties, the nucleotide as a whole acts as an acid, due to the phosphate group.

Glycolysis

Glycolysis is the metabolic pathway which converts glucose (C6H12O6) into pyruvate (CH3COCOO- + H+). Glycolysis is the anaerobic catabolism of glucose, occurring in virtually all cells. In eukaryotes, it occurs in the cytosol. The free energy, which is stored in 2 molecules of pyruvic acid, is somewhat less than that in the original glucose molecule. The free energy released in this process is used to form the high energy compounds, ATP (adenosine triphosphate) and NADH (reduced nicotinamide adenine dinucleotide).

Glycolysis is a definite sequence of ten reactions involving ten intermediate compounds, with one of the steps involving two intermediates. The most common type of glycolysis is the Embden-Meyerhof pathway, which was first discovered by Gustav Embden and Otto Meyerhof.

Glycolysis process explained by professor (video)