HISTAMINE Presents in nearly all animal tissue. Histamine stimulates glands in the stomach to secrete digestive juice, dilates the blood capillaries (important for increasing blood flow and decreasing blood pressure), increases permeability, causes contraction of the smooth muscles of the digestive tract, the uterus and the bronchia (in bronchial asthma). An anaphylactic reaction begins when the allergen enters the bloodstream and reacts with an antibody of the immunoglobulin E (lgE) class. This reaction stimulates cells to release histamine and other substances involved in immune inflammatory reactions. The first treatment for anaphylaxis is an apinephrine injection.

Serotonin Serotonin, also called 5-hydroxytryptamine (5HT), is synthesized and stored at several sites in the body. By far the largest amount of serotonin is found in cells of the intestinal mucosa, smaller amounts occur in the central nervous system, where it functions as a neurotransmitter, and in platelets. Serotonin is synthesized from tryptophan, which is hydroxylated in a BH 4 -requiring reaction analogous to that catalyzed by phenylalanine hydroxylase, the product, 5-hydroxytryptophan, is decarboxylated to serotonin, which is also degraded by MAO. Serotonin has multiple physiologic roles, including pain perception, regulation of sleep, appetite, temperature, blood pressure, cognitive functions, and mood (causes a feeling of well-being). Serotonin is converted to melatonin in the pineal gland via acetylation and methylation. Melatonin, a hormone that regulates the sleep-wake cycle, is reported to help with sleep disturbances caused by jet lag. Its effectiveness depends on taking the doses on a precise schedule. Melatonin products are nutritional supplements rather than prescription drugs.

Dopamine, norepinephrine, and epinephrine are biologically active amines that are collectively termed catecholamines. Dopamine and norepinephrine are synthesized in the brain and function as neurotransmitters. Norepinephrine is also synthesized in the adrenal medulla, as is epinephrine. Function: Outside the nervous system, norepinephrine and its methylated derivative, epinephrine, are hormone regulators of carbohydrate and lipid metabolism. Norepinephrine and epinephrine are released from storage vesicles in the adrenal medulla in response to fright, exercise, cold, and low levels of blood glucose. They increase the degradation of glycogen and triacylglycerol, as well as increase blood pressure and the output of the heart. Catecholamines

L-form of adrenalin is physiologically active, affecting carbohydrate metabolism and the circulatory system Stored in chromaffin granules and released into the blood upon nervous stimulation Activates, via adenylate cyclase, the liver and muscle phosphorylases (glycogenolysis) and the lipase of adipose tissue, leading to higher blood concentration of glucose, lactate and free fatty acids → higher oxygen consumption DOPAMINE Liver, lung, intestines – end product of tyrosine metabolism. Brain – neurotransmitter for central nervous system. Dopamine accounts 90 % of the total catecholamines. NORADRENALIN – in sympathetic nervous system acts as a adrenergic neurotransmitter causes contraction of blood vessels, with the exception of the coronary vessels causes an increase in the peripheral vascular resistance with consequent rise in blood pressure ADRENALIN

PARKINSON'S DISEASE Supportive treatment Rehabilitation Assessments by occupational therapists and physiotherapists are vital to maintain independence in activities of daily living for as long as possible. In the later stages of the disease, family support and daycare are very important. Specific treatment Antiparkinsonian drugs L -Dopa treatment – start with a small dose of a combination of L -dopa and peripheral dopa decarboxylase inhibitor and increase the dose if the response is inadequate. Selegiline (a monoamine oxidase type B inhibitor) is introduced early in the illness by some clinicians. Dopamine agonists (e.g. pergolide, lysuride, bromocriptine, apomorphine) may have a role in the later stages of the disease. Apomorphine is used for severe ‘on-off’ phenomena. Anticholinergic agents (e.g. benzhexol, orphenadrine) may be useful if there is a prominent tremor, but side-effects are common and these drugs have limited use in the elderly. Smaller more frequent doses of L -dopa and decarboxylase inhibitor (e.g. half a tablet six times a day instead of one tablet three times a day) are helpful for troublesome ‘on-off’ fluctuations. Drugs for other symptoms Laxatives for constipation. Antidepressants for depression. Analgetics for muscle aches.

- Degradation of catecholamines: The catecholamines are inactivated by oxidative deamination catalyzed by monoamine oxidase (MAO), and by O-methylation carried out by catechol-O-methyltransferase using SAM as the methyl donor. The two reactions can occur in either order. The metabolic products of these reactions are excreted in the urine as vanillylmandelic acid (VMA) from epinephrine and norepinephrine, and homovanillic acid from dopamine. -MAO inhibitors: MAO is found in neural and other tissues, such as the intestine and liver. In the neuron, this enzyme oxidatively deaminates and inactivates any excess neurotransmitter molecules (norepinephrine, dopamine, or serotonin) that may leak out of synaptic vesicles when the neuron is at rest. MAO inhibitors may irreversibly or reversibly inactivate the enzyme, permitting neurotransmitter molecules to escape degradation and, therefore, to both accumulate within the presynaptic neuron and to leak into the synaptic space.

Glu, Asp and some BCAA utilized as a fuel by the gut. Liver takes up % of the amino acids → conversion to glucose (gluconeogenesis). Pancreas is stimulated to release glucagon above fasting level (high uptake by the liver). In case of higher carbohydrate content → higher insulin/glucagon ratio → greater shift of amino acids away from gluconeogenesis into biosynthetic pathway. Most of amino acids in circulation is BCAA. HIGH PROTEIN MEAL

Absorptive (fed) state Amino acid metabolism in the liver 1. Increased amino acid degradation: In the absorptive period, more amino acids are present than the liver can use in the synthesis of proteins and other nitrogen- containing molecules. Amino acids are not stored, but are either released into the blood or are deaminated. The liver has limited capacity to degrade the branched-chain amino acids leucine, isoleucine, and valine. They pass through the liver essentially unchanged and are preferentially metabolized in muscle. 2. Increased protein synthesis: The body cannot store protein in the same way that it maintains glycogen or TAG reserves. However, a transient increase in the synthesis of hepatic proteins does occur in the absorptive state, resulting in replacement of any proteins that may have been degraded during the previous postabsorptive period.

1. AMINO ACID METABOLISM IN LIVER DURING FASTING. The major site of alanine uptake is the liver, which disposes of the amino nitrogen by incorporating it into urea. Alanine and other amino acids are oxidized and their carbon skeletons converted principally to glucose. Glucagon and glucocorticoids stimulate the uptake of amino acids into liver and increase gluconeogenesis and ureagenesis. 2. RELEASE OF AMINO ACIDS FROM SKELETAL MUSCLE DURING FASTING. Skeletal muscle oxidizes the BCAA to produce energy and glutamine. The amino groups of the BCAA, and of aspartate and glutamate, are transferred out of skeletal muscle in alanine and glutamine. The release of amino acids from skeletal muscle is stimulated during by the increase of insulin and increase of glucocorticoid levels in the blood.

Principles governing amino acid flux between tissues. The pattern of interorgan flux of amino acids is strongly affected by conditions that change the supply of fuels and by conditions that increase the demand for amino acids (metabolic acidosis, surgical stress, traumatic injury, burns, wound healing, and sepsis). The flux of amino acid carbon and nitrogen in these different conditions is dictated by several considerations: 1. Ammonia (NH 3 ) is toxic. Consequently, it is transported between tissues as alanine or glutamine. Alanine is the principal carrier of amino acid nitrogen from other tissues back to the liver. 2. The pool of glutamine in the blood serves several essential metabolic functions. 3. The BCAA can be converted to tricarboxylic acid cycle intermediates and used as fuels by almost all tissues. 4. Amino acids are major gluconeogenic substrates, and most of the energy obtained from their oxidation is derived from oxidation of the glucose formed from their carbon skeletons. 5. The relative rates of protein synthesis and degradation determine the size of the free amino acid pools available for the synthesis of new proteins and for other essential functions. Utilization of amino acids by kidney One of the primary roles of amino nitrogen is to provide ammonia in the kidney for the excretion of protons in the urine. NH 4 + is released from glutamine by glutaminase and by glutamate dehydrogenase. Functions of glutamine Protein synthesis Ammoniagenesis for proton excretion Nitrogen donor for synthesis of: Purines Pyrinidines NAD+ Amino Sugars Asparagine Other compounds Glutamate donor for synthesis of: Glutathione GABA Ornithine Arginige Proline Other compounds

Glutamine (glutaminase) → glutamate (glutamate dehydrogenase) → NH α-ketoglutarate (as a fuel oxidized to CO 2, converted to glucose, converted to Ala). Glutamine uptake depends on the amount of acid which must be excreted to maintain a normal pH in the blood. During metabolic acidosis, the excretion of NH 4 + by kidney increases severalfold (Gln → 2/3 of NH 4 + ). Ammonia increases proton excretion by combining with a proton to form ammonium ion in the renal tubular fluid. The protons in tubule fluid are buffered by phosphate, bicarbonate or NH 3 which can diffuse through the membrane of renal tubule cells into the urine. Combining with proton → cannot be transported back. UTILIZATION BY KIDNEY