Pantothenic Acid is widely distributed in nature and is found in nearly all plant an animal foods. Good sources include: Meats (esp. liver), egg yolk, legumes, whole-grains, potatoes, and avocados (low in fruits).
How is pantothenic acid ingested and absorbed?
85% of pantothenic acid in food is bound as a component of coenzyme A. During digestion: CoA is hydrolyzed to pantotheine, and pantotheine is converted to pantothenic acid. Absorption: low concentrations are Na-dependent, active (Sodium- Dependent Multivitamin transporter SMVT w/biotin) and high concentrations are absorbed through passive diffusion.
Higher concentrations of pantothenic acid are found more often....
intracellularly than extracellularly due to its rapid conversion to CoA
What is the function of Pantothenic Acid?
it is a component of coenzyme A and 4' - phosphopantetheine, these function as transporters of acetyl and acyl groups (2-13 C).
Explain CoA synthesis
1) Pantothenic acid is phosphorylated by pantothenate kinase (rate-limiting) to form 4'-phosphopantothenic acid. 2) 4'-phosophopantothenic acid reacts with cysteine forming a peptide bond. 3) a carboxyl group from cysteine is removed to form 4'-phosphopantetheine. 4) ATP reacts with 4'-phosphopantetheine to form dephosphocoenzyme A : AMP is added. 5) Phosphorylation of the dephosphocoenzyme A generates CoA
Bioavailability of Pantothenic Acid
the intake as a whole is decreasing due to a large dependence of commercially prepared foods. Heating, canning, and milling destroys it.
How do CoA and 4'-phosphopantetheine participate in nutrient-metabolism?
these function as transporters of acetyl and acyl groups (2-13 C): 1) degredation reactions (energy production) such as metabolism of CHO, lipids and proteins; Pyruvate converting into acetyl CoA then going into the TCA; and works with thiamin, riboflavin, and niacin in the oxidative decarboxylation of pyruvate. 2) Synthesis reactions (lipid metabolism) such as the synthesis of cholesterol, bile, ketones, fatty acids, steroid hormones. 3) Regulation of protein function such as Acetylation (activity, localization, and function)
How does Pantothenic acid participate in fatty acid synthesis?
Pantoothenic acid is a component of the carrier arms of ACP which is essential in fatty acid synthesis. Sulfhydryl group in 4'-phosphopantetheine and in the CE protein are the active sites for the transfer of acyl chains.
Pantothenic acid deficiency
very rare (alcoholics, diabetics, IBD): 1) Burning foot syndrome- abnormal sensations of the feet and lower legs, exacerbated by warmth and diminished with cold. 2) other symptoms- weakness;fatigue, impaired muscle coordination, staggering gait, insomnia, nausia, cramps, vomiting, paresthesia of extremities.
What are some ways to assess Panthothenic Acid status?
1) frequently accessed by measuring the urinary pantothenate (excretion less than 1 mg/d is considered to be indicative of a poor status). 2) Blood levels are also used to assess status (blood pantothenate below 100 ug/dL may be indicative of low dietary pantothenate intake).
Which structural part of Biotin is important about it?
It has two five membered rings and the valeric acid is very important because it helps biotin to bind to things.
What are some sources of Biotin?
1) it is synthesized by intestinal bacteria 2) it is present in abundant supply: humans pass more biotin in their urine and feces that they consume. Experimental anymals must be prevented from practicing coprophagy to produce deficiency. 3) the best sources in food are liver, soy beans, egg yolk, cereals, legumes, and nuts.
How is biotin found in foods?
it is bound to lysines, always bound to proteins.
Is the synthesis of biotin in the body enough to meet needs?
What is Avidin?
it is a special glycoprotien found in raw eggs that binds to biotin very tightly and prevents its absorption and utilization. It is the strongest non-covalent bond in nature. It is however destroyed when cooked.
What is human biotin deficiency usually associated with?
A high intake of raw eggs or a metabolic abnormality. Body builders are succeptible because they eat lots of raw eggs.
What does eating too many raw eggs result in?
hair loss, dermatitis, neuromuscular defects all due to avidin.
Bioavailability considerations of Biotin
Its absorbed as biotin; protein-bound biotin requires normal protein digestion to yield: biotinyl peptides -> further cleaved to yield biocytin->(via biotinidase) free biotin.
What is biocytin?
it is biotin with a lysine attached to it
What is biotinidase?
it hydrolyzes the biocytin to biotin. it is located on the intestinal brush border and in pancreatic secretions. At acid pH, it cleaves biocytin to yeild biotin and lysine. At allkaline pH, it does the same except it also binds to biotin. Biotinidase deficiency is an autosomal recessive inborn error of metabolism. Treatment is free biotin.
Absorption, Transport, and Storage of Biotin
1) absorption occurs through the sodium-dependent multivitamin transporter (SMVT; along with PA and lipoic acid) or by SLC19A3 (along with thiamin) a physiological concentrations. 2) Abs. occurs by passive diffusion at pharmacological doses. 3) found in circulation as free biotin (~80%); rest is bound to alpha and beta globulins. 4) taken up by tissues by SMVT, monocarboxylate transporter (MCT) and SLC19A3.
What does PA stand for?
What is the function of Biotin?
it plays a direct role in the movement of carboxylases. Cofactor roles: covalent attachment to 4 enzymes (carboxylases) in 1) gluconeogenesis - pyruvate carboxylase. 2) amino acid catabolism - 3-methylcrotonyl CoA carboxylase (leucine) and propionyl CoA carboxylase (methionine). 3) Fatty Acid Synthesis - Acetyl CoA carboxylase.
Functions of Biotin: how is biotin bound to enzymes?
Biotin is covalently bound to each enzyme (apoenzyme --> haloenzyme). catalyzed by holocarboxylase synthetase, requires ATP and Mg, and occurs in two-steps. 1) Biotin reacts with ATP in a Mg-dependent reaction -> biotinyl adenosine monophosphate (activated biotin). 2) Reacts with apocarboxylase to form holocarboxylase (carboxy terminus of valeric acid linked by an amide linkage on a lysine)
Functions of Biotin: fatty acid synthesis
ACP: acyl carrier protein. CE: condensing enzyme. Sulfhydryl groups in ACP and CE are the active sites for the transfer of acyl chains. Series of reduction and dehydrogenation reactions to elongate the chain. (the sulfide groups come from the cysteine from PA)
Functions of Biotin: non-coenzyme roles
1) attachment to histones (H2A, H2B, H3, H4) via holocarboxylase synthetase and biotinidase. 2)regulates cell cycle, gene slicing and DNA repair. 3) more than 200 genes are regulated by biotin (positive and negative) through transcription factors such as cGMP, NF-KB, Sp1, Sp3.
Biotin deficiency assessment
Biotin plays a role in amino acid catabolism (B-methylcrotonyl CoA Carboxylase). Since this enzyme is biotin dependent, if there is no biotin, it will convert itself to 3-hydroxyisovalerate. So, if there is an abundance of 3-hydroxyisovalerate in the urine, it will be a mark of biotin deficiency. Its also measured by decreased biotin in the urine.
How is Biotin intake measured/regulated?
Adequate intakes, no reported UL (metabolites from the catabolism of valeric acid side chain-bisnorbiotin and tetranorbiotin are excreted in the urine)
1) very rare in humans and reversible. 2) produced experimentally in people eating 30% of their calories as raw egg white and a low biotin diet. 3) Symptoms of biotin deficiency include: Lethargy, Depression, Hallucinations, Muscle pain, anorexia, alopecia (hair falls out), and dermatitis. 4) seen in individuals who consume raw eggs, IBD, achlorhydra, alcoholics, genetic mutations in biotinidase and holocarboxylase synthetase.
Biotin Deficiency in animal models
1) by feeding avidin (raw egg white) 2) by feeding a diet low in biotin and simultaneously destroing the microflora from the gut with antibiotics. 3) by feeding a diet free of biotin and preventing coprophagy. 4) Symptoms: Dermatitis - first seen around they eye "spectacle eye" (bc of rapid turnover), Swelling of joints;paws hypersensitive to pain, Jumping gait- kangaroo-like posture.
Main facts of Magnesium
It is a cation and it is an essential nutrient. In humans, it ranks 4th in abundance and intracellularly it is second to potassium (macromineral). It is only found in the diavalent state.
What are some sources of Magnesium?
chocolate, nuts, legumes, whole-grains, seafood, green leafy vegetables (chlorophyll). Food processing (grain refining) may substantially reduce the magnesium content of some foods.
Bioavailability of Magnesium
1) Things that impair absorption: Fiber, phytates (minimal), Ca, P(competition), fatty acids (soaps). 2) Things that enhance absorption: carbohydrates (fructose and lactose); protein, vitamin D.
What are phytates?
they are found in plants, six ring structure with phosphates at every point. this binds to things and prevents them from being absorbed. Usually binds to positively charged molecules.
How is magnesium absorption and transport regulated?
it is homeostatically regulated; mechanisms are unknown; likely involves absorption across the gut, renal excretion, and transmembrane cation flux (Ca).
Absorption of Magnesium
the mechanism of absorption is not clear: 1) a saturable, carrier-mediated active transporter at low magnesium intakes, mainly distal jejunum, ileum, and colon. 2) Transporter associated with a Transient Receptor Potential cation channel (TRPM6), regulated by high intracellular Mg levels. 3) absorption ranges from 20-60% intake. Absorption lowers at higher intakes.
Transport of Magnesium
1) once taken up by enterocytes, Mg is likely effluxed via a Na- and ATP-dependent carrier and possibly a Ca-dependent carrier. 2) in plasma: it is tightly maintained between 1.6-2-2 mg/dL, 50-55% is free, ~ 33% is bound to protein (albumin), ~13% is complexed with other ions. 3) about 1/3 of the Mg in bone is loosely bound to the surface of the bone crystals, this makes it an exchangable pool with plasma.
Excretion of Magnesium
1) the majority of excretion is via the kidneys. 2) of the filtered Mg: 65% is reabsorbed in the loop of henely, 20-30% is reabsorbed in the proximal tubule, only 5% of filtered Mg is excreted, excretion is inversely related to intake, PTH inhibits Mg excretion by facilitating its reabsorption in the tubule. 3) fecal Mg represents unabsorbed Mg. 4) Mg may be lost in sweat (~15mg/d)
Functions of Magnesium
(overall, stability and sometimes activity). Mg is bound to phospholipids in cell membranes (stability). More than 300 enzymes require Mg as a cofactor: 1) enzymes that require ATP and ADP (~90% of Mg) - Hexokinase and phosphofructokinase (glycolysis), Glucokinase, Transketolase (hexomonophospate shunt), Oxidative decarboxylation (Krebs cycle), Acyl CoA synthetase (beta-oxidation initiation). 2) Regulatory roles - Transcription, Protein synthesis, cyclic AMP formation, Cardiac and smooth muscle contraction
Magnesium's interaction with Ca/P metabolism
1) Mg and Ca have overlapping transport systems: disturbances in the metabolism of one often distrubs the metabolism of the other (direct competition). 2) Mg is required for parathyroid hormone (PTH) secretion (high Mg inhibits PTH release). PTH functions to increase Ca (bone reabsorption; kidney reabsorption; intestine absorption). 3) Vitamin D hydroxylation in the liver requires Mg, it converts it to its active form. 4) Mg inhibits phosphorus absorption: phosphorus reduces Ca absorption. 5) inhibits intracellular Ca release from SR. 6) competes with Ca for binding sites on troponin C inhibiting muscle contractions. 7) inhibits blood clotting.
1) very rare in healthy humans: pure deficiency has not been reported. Symptoms include nausea, vomiting, anorexia; tetany and convulsions; hypoCa (decreased PTH, decreased Ca abs), hypo Na, hypo K, abnormal neuromuscular and neurological functions. 2) magnesium deficiency is usually associated with other pathological conditions: alcoholics are frequently magnesium deficient because it increases Mg excretion. [glucose, lipid, electrolytes]- CVD, vomiting/diarrhea, severe PEM, renal diseases and diabetes.
How are magnesium intakes regulated/measured?
1) magnesium toxicity with excessive intakes is rare. can occur in people with impaired renal functions (if renal function is imparied, you wont be able to control reabsorption bc they cannont excrete Mg normally). the tolerable upper level is 350 mg for nonfood sources. 2) there is an RDA. 3) Mg decreases diarrhea...Milk of magnesium: Mg travels down and pulls water into the colon because of its positive charge, and since it goes all the way down there because thats where its absorbed,the water will go into your colon.
How can you assess Magnesium status?
1) assessment is difficult because only 1% of the Mg is found extracellularly. 2) Serum Mg concentrations are the most routine measurement. if serum magnesium is low, an inadequate amount of magnesium is present intracellularly. 3) renal excretion reflects mg status. excretion decreases with deficiency. decreased excretion determined over two (24 hour) periods following a Mg load indicates deficiency.
How is chromium related to insulin?
1) the release of insulin from the Beta-cells of the pancreas stimulates the release of GTF. This is thought to form a disulfide bridge between insulin and the insulin receptor. However, there is no direct evidence of this. 2) recent studies have demostrated that Cr may be involved in Pancreatic insulin secretion, insulin receptor production, expression, and/or activity, and enhanced insulin effectiveness.
What is the proposed model of chromium and insulin?
Increases in plasma insulin cause more Cr uptake by cells. In cells, 4 Cr to bind to apochromodulin to form chromodulin (gly-cys-asp-glu). Chromodulin binds to the insulin receptor and stimulates kinase activity. The kinase activity is responsible for insulins activity (GLUT4) and it activates the enzymes involved in nutrient metabolism.
Chromium and weight loss
several studies have been reported on blood glucose and lipid profiles following Cr supplementation. No Significant Effects on Strength, Muscle gain, or Fat loss!
Excretion of chromium
1) most absorbed Cr is excreted from the body in urine. ~ 95 % of Cr excretion via urine; reflects recent intake. Urinary chromium is ~0.2 - 0.4 ug/day. Diets high in simple sugars has been shown to raise urinary chromium in some subjects by 300%. 2) there are no reliable markers. Some could be plasma Cr, response to Cr load, urinary Cr, and hair Cr.
Human Chromium Deficiency
1) humans have maintained on total parental nutrition (TPN; from 5 months to 3.5 years) have developed abnormal glucose tolerance tests that were not responsive to insulin. Patients had increased blood glucose levels, glycosuria, and were not responsive to insulin. Addition to Cr to the TPN solution corrected the condition. 2)Signs and symptoms: weight loss, peripheral neuropathy, elevated plasma glucose concentrations (insulin resistance), and high plasma free fatty acid concentration. 3) Cr needs may be increased during diabetes.
Characteristics of chromium
1) a metal, several oxidations states: Cr-2 through Cr +6. 2) found in air, water, and soil. 3) often binds to nitrogens, oxygens, or sulfur groups. 4) ultra trace nutrient, not thought of as an essential nutrient. 5) the most soluble form is Cr +3. 6) Cr +6 is toxic
1) inhibitors (olation): ingestion of antacids, phytates (cr binds to phytates and then are excreted in feces). 2) Enhancers (improves solubility by converting it to the Cr+3 state): amino acids (methionine and histidine), vitamin C, cooking with stainless steel cookware (esp acidic foods).
Absorption, Transport, and Storage of
1) chromium is thought to be absorbed throughout the small intestine (unknown mechanism): passive diffusion or by carrier-mediated transport, about 0.4 - 2.5 % of chromium is absorbed. 2) in the blood, Cr primarily binds to trasferrin (iron transporter) for transport; albumin and then globulins and lipoproteins at high concentrations. 3) Storage occurs in kidney, liver, muscle, pancreas, and bone (possible stored with ferric iron).
Functions of Chromium
1) chromium potentiates the action of insulin. Exact molecular mechanism of action is unknown. Generation of a complex with nicotinic acid and amino acids to form glucose tolerance factor (GTF)? 2) GTP was first identified in brewer's yeast. it is biologically active; dinicotinato-chromium complex. Initial product of in vivo synthesis was a tetra-aquo dinicotinado chromium. Water molecules are replaced by amino acids (glutamate, cysteine and glycine) which stabilizes the protein.
1) oral supplement of up to 1000 ug of Cr appears to be safe. 2) Chromium picolinate (most common supplement): renal faliure, hepatic disfunctions in humans, chromosomal damage. 3) Cr 6+ (hexavalent) is highly toxic: Hexavalent chromium (dicrhomate) can be absorbed through the skin, inhaled, absorbed in diet. Oral Cr +6 is 10 to 100 times more toxic than cr +3. COAEL is set at 1000 ug/day.
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