the-psoriasis-treatment

The way the Atkins Diet or any low-carb diet for weight loss works is by limiting the presence of glucose so as to encourage fatty acids to be converted by the liver into ketone bodies. When ketone bodies accumulate in the blood, they lower the pH of the blood. This is a state called ketosis, which is basically when glucose use for energy is slowed down and fatty acid use for energy is sped up. If too many ketone bodies build up, however, then hyperketonemia results and possibly dangerous ketoacidosis. After a good night's sleep, it's known that the fasting state will increase amount of ketone bodies a little, because of depleted glycogen stores. But after 2 days ketone bodies can rise 140-fold. In early starvation, the muscle will use ketone bodies, but then changes to use of fatty acids so that the ketone bodies can be used for the brain. Prolonged starvation causes ketones to become the dominant fuel for the brain, to spare amino acids and loss of muscle. The dramatic rise o...

Fatty acid oxidation is dependent on entry of fatty acids into the mitochondria, which provides substrate for beta-oxidation in the mitochondrial matrix. The fatty acids are transported in as acylcarnitines. Step 1 in beta-oxidation happens when a fatty acyl CoA that's made at the inner surface of the inner mitochondrial membraine is oxidized by acyl-CoA dehydrogenase. The flavoprotein enzyme uses FAD to accept an electron to complete the reaction. The products end up being trans-enoyl CoA and FADH2, which transfers electrons into the oxidative phosphorylation pathway to recreate FAD. Step 2 in beta-oxidation is hydration of trans-enoyl CoA producing 3-L-hydroxyacyl CoA. Step 3 is when 3-L-hydroxyacyl CoA is oxidized to 3-ketoacyl-CoA intermediate and generates NADH. Step 4 occurs when beta-ketoacyl-CoA thiolase cleaves the 3-ketoacyl-CoA to produce a 2-carbon atom short fatty acyl-CoA and acetylCoA. Acetyl CoA is then ready to enter in the TCA cycle for ATP energy production, and ...

Once the “war on cancer” was declared in 1971 by Congress, researchers have sought to defeat it (1), but after losses of many knights in shining armor, a newfound respect has come around for this dragon of a disease (1). In the 1990s and 2000s, however, a new sense of hope had come about. “End cancer by the year 2015” was the message shared in 2003 by Andrew C. von Eschenbach, MD, director of the National Cancer Institute (NCI). And although he’s had many critics saying it couldn’t be done, others joined him in saying it could. Just two years afterward, in 2005, NCI modified it’s lofty goal to a softer “alleviate pain, suffering and death associated with cancer” (2). The change meant a new direction of “controlling” but not “curing” the disease . The same year, 2005, one Eschenbach supporter put forward a plan for a victory (3). His name was Mikhail V Blagosklonny, MD, PhD, and his approach was by combining strategies that target cancerous cells directly while protecting normal cells i...

The biochemical mechanism by which metals are mutagenic is by their effects on DNA. The main pathway shared by iron, copper, chromium, vanadium and cobalt is by redox-cycling reactions and mercury, cadmium and nickel by depleting glutathione and bonding to sulfihydryl groups (1). Free iron, in particular, can cause oxidative damage on DNA that can cause cancer in the spleen (2). Arsenic, in particular binds directly to critical thiols producing DNA damage (1). Cadmium interferes with and inhibits DNA repair (3;4). Reference List 1. Valko M, Morris H, Cronin MT. Metals, toxicity and oxidative stress. Curr Med Chem 2005;12:1161-208. 2. Wu X, Kannan S, Ramanujam VM, Khan MF. Iron release and oxidative DNA damage in splenic toxicity of aniline. J Toxicol Environ Health A 2005;68:657-66. 3. Slebos RJ, Li M, Evjen AN, Coffa J, Shyr Y, Yarbrough WG. Mutagenic effect of cadmium on tetranucleotide repeats in human cells. Mutat Res 2006;602:92-9. 4. Giaginis C, Gatzidou E, Theocharis S. DNA...

Calcium (Ca) and magnesium (Mg) are non-heavy metals with the same valence charge that are both critical for physiologic function, yet overlap each other in their mechanisms. For example, they both use the same transport systems in kidney competing with each other for absorption. They also oppose one another in blood coagulation, smooth muscle contraction and PTH release. The relationship between Ca and Mg is important as it promotes a balance in given biological systems for proper function of the body. Deficiency either mineral could result in an improper balance leading to problems.

Estrogen appears to directly influence bone turnover. Its mechanism is byacting on estrogen receptors in bone cells (1). The hormone influencesvitamin D metabolism by increasing conversion of 25-hydroxyvitamin D(25OHD) to 1,25-(0H)2D as it does in birds (2). The increase of 1,25-(0H)2D then enhances calcium absorption in the bones(2). Estrogen, thereby, contributes to bone density by slowing down boneloss and its absence can lead to lower bone density and predispose forosteoporosis (1;2). This biochemistry supports evidence that already exists that estrogenreplacement therapy (ERT) combined with adequate calcium and vitamin Dintake as well as exercise may help prevent osteoporosis (3;4). Despite the effects, however, I have the same opinion about using long-term estrogen replacement therapy (ERT) in postmenopausal women for osteoporosis as I do about estrogen for reducing risk of cardiovascular disease in postmenopausal women. While there are benefits outlined suggesting that future re...

Summary: Complementary preventive therapy for Alzheimer’s disease should include DHA for its biochemical implications, especially in apoE4-genotype obese-diabetic patients. DHA mechanisms involve reducing adiposity and secretions, improving insulin sensitivity, guarding against oxidative stress, and guarding against beta-amyloid plaque, neurofibrillary tangles and advanced glycation end-products. Background: Urgent Call for Alzheimer’s Disease Preventive Therapies Foresight warns that the present epidemic of obesity and diabetes in the United States of America will lead to future medical epidemics and among them will be Alzheimer’s disease (AD), the most common neurodegenerative disease seen in aging. AD is seriously debilitating and at present time has no cure. Current treatments are limited to cholinesterase inhibitors to improve function of signaling pathways in memory, but are not intended to prevent or slow further brain damage. Preventive strategies are currently being studied to...

Armour thyroid is the "natural" therapy from dessicated porcine thyroid gland while Synthroid is produced synthetically as levothyroxine. Armour thyroid contains both T3 and T4 while Synthroid only contains T4. There is debate on whether or not use of both or one is better. Synthroid came into use because it was standardized unlike the natural kind, which varied a lot from batch to batch. But it turns out that patients often don't like T4 alone as much as the natural T3/T4. A new synthetic T3/T4 is now on the market as Liotrix, but is expensive. Reference http://www.netwellness.uc.edu/question.cfm/24516.htm

To regulate basal metabolic rate, the thyroid gland synthesizes hormones thyroxine, or triiodo-L-thyronine (T4), and the more active triiodo-L-tyronine (T3) (1).When secreted into the bloodstream, they associate with transport proteins (thyroxine-binding globulin, albumin, and transthyretin), which circulate the hormones (2). There is nearly 50 times T4 than there is T3, but T3 is more potent. T4 and T3 bind to nuclear receptors that affect gene expression. Increased mRNA and protein synthesis appear to lead to stimulation of oxygen consumption (when awake, at rest or fasting), heat production and also influences enzymes involved in carbohydrate metabolism (3;4). Reference List 1. Devlin TM. Textbook of Biochemistry with Clinical Correlations. Philadelphia: Wiley-Liss, 2002. 2. Gropper SS, Smith JL, Groff JL. Advanced Nutrition and Human Metabolism. Belmont, CA: Thomson Wadsworth, 2009. 3. Pereira BM, Balasubramanian K, Govindarajulu P. Effect of thyroxine treatment on epididymal c...

Korsakoff’s syndrome, or Wernicke encephalopathy, is a serious neurological disorder occurring under conditions of thiamine deficiency. It’s usually caused by long-term abuse of alcohol, which breaks down thiamine in the body. It is characterized at autopsy by lesions in the brain stem. Thiamine is necessary for proper glucose metabolism in the brain (1). As a B vitamin it acts as a cofactor for enzymes in the Krebs cycle including pyruvate dehydrogenase. Brain insults result when metabolism is inhibited, particularly where there is high demand for energy. A cascade of injury to the brain occurs when neuronal death reduces production of succinate and GABA as well as neuron stimulation. Without functioning pyruvate dehydrogenase, lactic acid production increases. Nucleotide synthesis and NADPH production is reduced, which in turn reduces glutathione in blood cells. Individuals carrying apolipoprotein E (ApoE) epsilon 4 (E4) allele are at higher risk of Korsakoff’s syndrome (2). Thus, t...

Type 2 diabetes mellitus is considered a major risk factor in cardiovascular disease (CVD) in both men and women, but CVD pathogenesis biochemistry can differ between the sexes. Both sexes are affected by insulin resistance, which generally precedes the diabetes, and accompanying metabolic syndrome factors dyslipidemia and hypertension (1). The insulin resistance leads to elevated insulin levels, which stimulates sodium reabsorption. The sodium levels can induce prolonged hypertension. The hypertension leads to hardening of the arteries and eventual atherosclerosis. The chronic hyperglycemia leads to glycation of myocardial proteins and microvascular disease (1;2). Gradual nerve damage from abnormal signaling leads to autonomic neuropathy (2). Although women have overall lower risk of heart disease than men before age 60 due in part because of estrogen, diabetes abolishes difference in CVD risk. In fact, diabetes in women is reported to increase risk of CVD three- to seven-fold whereas...

Menopause is the eventual reduced production of sex hormones in women. Follicular cells in the ovaries appear to become exhausted by continual cycles of ovulation and atresia (1). The ovaries become less responsive to stimulation from gonadotropin—follicle-stimulating hormone (FSH) and luteinizing hormone (LH)—causing estrogens and progesterone levels to lower. The ovaries degenerate causing further diminished estrogen production until the hormone is only produced in limited amounts by other tissues (1). The loss of estrogens production also reduces cardioprotective effects of this particular hormone. Estrogens, estradiol in particular, protects cardiovascular health because of its binding to estrogen receptors (ERs). ERs in absence of estrogen are associated with heat shock protein (HSP); estrogen binding promotes dissociation (2). Estrogen binding also changes gene transcription, altering levels and kinds of cellular proteins (2). The alterations directly affect myocardial, vascular ...

Connecting the biochemical dots that lead to atherosclerosis is what is best attempted by the term metabolic syndrome (MS) (1). The term, of which is still under controversy, is used as a predictor of cardiovascular disease and type 2 diabetes mellitus (2-4). MS can begin with abdominal obesity (MS dot 1), a consequence of overeating and a sedentary lifestyle (1;5). The additional adipose tissue can then reduce affinity of insulin receptors and/or create abnormal post-receptor responses resulting in insulin resistance (MS dot 2) (1). Once insulin resistance overwhelms capacity to produce insulin to overcome it, then type 2 diabetes mellitus (T2DM) ensues (1). T2DM is accompanied by hyperglycemia and often by hyperlipidemia (MS dot 3) (1). The hyperlipidemia results because VLDL and chylomicrons are not cleared by the enzyme lipoprotein lipase of which is dependent on insulin (1). The high levels of free fatty acids then impair insulin action further (1). Plus, new research suggests tha...

Glycosylated hemoglobin forms when prolonged hyperglycemia leads to glucose in the blood not used for energy to attach itself to hemoglobin (1;2). The reaction does not require an enzyme, but occurs spontaneously (1). The concentration of glycosylated hemoglobin determined by an assay can be used to determine the status of a diabetic patient and effectiveness of treatment (1;2). The glycosylated hemoglobin assay has been found to be a more effective tests than others such as the oral glucose tolerance test for the detection of diabetes (3). Reference List 1. Devlin TM. Textbook of Biochemistry with Clinical Correlations. Philadelphia: Wiley-Liss, 2002, pp893-4. 2. Diabetes and Hormone Center of the Pacific. Glycosylated hemoglobin testing. Available at: http://www.endocrinologist.com/Hemoglobin.htm 3. Dods RF, Bolmey C. Glycosylated Hemoglobin Assay and Oral Glucose Tolerance Test Compared for Detection of Diabetes Mellitus. Clin Chem 25/5, 764-768, 1979. Available at: http://www.clinc...

Despite controversy over the current definition of "metabolic syndrome", physicians are using it as a useful clinical tool. It can be used to help with counseling patients and to recommend treatments. Metabolic syndrome is currently defined as a combination of several risk factors that ultimately lead to diabetes and cardiovascular disease. They include obesity, hypercholesterolemia, hyperlipidemia, hypertension, insulin resistance and inflamation (1). Each of the several risk factors that makes up metabolic syndrome requires varying treatments, so physicians may find that lumping them together is not useful. In fact, controversy exists on if the term "metabolic syndrome" is even defined correctly (1). But a 2007 Mayo Clinic meta-analysis found that metabolic syndrome is beginning to find development as a useful clinical tool (2). The review focused on heart disease factors and found that metabolic syndrome increased risk strongly (2). Reference List 1. Cheng AY, Le...

Allosteric enzymes are those that are controlled by the binding of an allosteric effector. The effector may be positive or negative in activating or inactivating the enzyme, respectively, and creates a conformational change of the enzyme. The product may be the allosteric effector in itself producing feedback or feedforward control. There are two classes of allosteric enzymes based on the effect of the effector on Km and Vmax. If the effector alters Km it is in K class and if the effector alters Vmax it is in V class. There are also enzymes that have both Km and Vmax affected. K class allosteric enzymes are affected by negative effector binding because it affects the affinity of the binding site for the substrate. V class allosteric enzymes are affective positively or negatively by effectors that increase or decrease rate of enzyme-substrate complex breakdown to products. Given the conformational change and resulting activation and inactivation of an enzyme, catalysis of reactions woul...

Hormones are any substance in the body that carries a signal to regulate growth, differentiation and function of a variety of cells. The more signals needed, the more hormones in an organism. The big-brained human body is no different. In higher animals signal pathways of many hormonal systems originate in the brain. Because hormones are so specific in communicating between cells, we can expect yet more discovery of hormones in the future to add to the large number already found. Their are major categories of hormones: peptide and protein, thyroid, catecholamine and steroid. The hormones are specific in targeting cognate receptors that are expressed for specific hormones (1). For example, catecholamine hormones epinephrine and norepinephrine as well as peptide hormones target specific cell surface receptors while steroid hormones target intracellular receptors. Endocrine hormones are those synthesized in a gland and travels to reach distant target cells. Paracrine hormones are secreted...

What are the specific reasons for hypoglycemia seen in hereditary fructose intolerance? Hereditary fructose intolerance (HFI) an autosomal recessive disorder in which there is subnormal activity of the enzyme fructose 1-phosphate aldolase B (1;2). Largely found in the liver, the enzyme is needed for normal fructose metabolism for splitting fructose 1-phosphate to form dihydroacetone and glyceraldehyde (1). Hypoglycemia after consumption of fructose (also sucrose or sorbitol) results because of the lack of maintenance of proper blood glucose levels by the liver (2). The fructose ingestion and the lack of aldolase B results in the accummulation of fructose 1-phosphate in cells, particularly in the liver (1). The accumulation leads to depletion of Pi, which in turn keeps mitochondria in hepatocytes from producing ATP causing cell damage, and inhibition of glycogenolysis and, thus, guconeogenesis (1;2). HFI often goes unrecognized and is life-threatening due to hypoglycemia along with poss...

Micelles are made up of amphipathic compounds such as bile acids, fatty acids and monoacylglycerols that interact leaving a relatively stable hydrophilic surface and hydrophobic interior (1). They form at certain temperature ranges when a mixture of lipids is present in concentrated amounts (1). Fatty acid and phospholipid micelles are spherical, but pure bile acid micelles are sandwich-shaped rectangles (1p1062). During lipid digestion after hydrolysis of triacylglycerols by lipases, it’s up to the bile acid sandwiches to solubilize the spheres, thereby forming “mixed” micelles that appear not unlike rods (1p1062). These rods become longer as more lipids (including limited cholesterol) are solubilized (1p1062). The bile acid micelles form at concentrations of 2-5 mM and at pH values above pK, meaning in equilibrium with other micelles in solution (1p1061-2). From the lumen, the micelles then transfer the lipids to the mucosal surface for absorption by diffusion (1p1063). Lipid-soluble...

When studying the evolution timeline that led to modern biochemistry, one can always turn to studying protein architecture. Proteins have been called “molecular fossils” that serve to mark milestones in the “history of life” (1). There is a wide diversity of proteolytic enzymes in humans and the network of enzymes have a grand complexity that calls for investigation of how they were shaped over time (2). In digestion there is a variety of proteolytic enzymes—pepsins, enteropeptidases, carboxypeptidases, and aminopeptidases (3). Each work to hydrolyse proteins by cleaving off amino acids from differing peptide bonds, in different stages and conditions (gastric, pancreatic and intestinal phases) and at varied pH ranges (3). The system is indeed complex, not exactly perfect (a better system may have used only a one or two enzymes), but it works and that's evolution. Each highly structured enzyme would have evolved accordingly at some time, and some, which may have had major roles in t...