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Spring 2014 > Metabolism - Exam #2, Part 1 > Flashcards

Metabolism - Exam #2, Part 1 Flashcards

1
Q

Who discovered the first VITAMIN in the early 20th century?

A
  • Casimer Funk;
  • From rice polishings and was an anti beriberi substance;
  • “Vitamine” = amine vital for life
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2
Q

Why was the name changed to just Vitamin?

A
  • “Vita” means “life” in Latin;

- But found that only a few substances were actually amines

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3
Q

What was the main reason for the discovery of Vitamins?

A
  • Because of their ABSENCE in diets of animals and people;
  • Found due symptoms that developed from DEFICIENCIES!!;
  • Today more is known about deficiency than sufficiency for optimal health
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4
Q

What is the key focus of Interactions?

A
  • Think more about what the vitamin DOES than what happens if it is deficient;
  • Sometimes difficult to relate function to deficiency;
  • Focus now should be on OPTIMAL HEALTH, not just avoiding deficiency
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5
Q

How were the chemical structures/ of Vitamins discovered?

A
  • Isolation and synthesis;

- Each was then given a name of a single substance, but it was discovered that vitamins may have a VARIETY of FUNCTIONS

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6
Q

What are Vitamers?

A
  • Vitamin activity may be found in several closely related compounds;
  • One or more related chemical substances that fulfill the same specific vitamin function;
  • EX: Vitamin A with retinol, retinal, and retinoic acid that can have different functions
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7
Q

What are Vitamins?

A
  • Organic compounds with regulatory functions;
  • Essential nutrients that cannot be synthesized or not in adequate amounts;
  • Not chemically related to each other;
  • Fat-Soluble = A, D, E, K;
  • Water Soluble = Vit. C and B-Vits
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8
Q

How do Fat-Soluble Vitamins travel in the body?

A
  • Fat-soluble vitamins bypass the liver like fats;

- Travel through the Lymph

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9
Q

How do Water-Soluble Vitamins travel in the body?

A
  • Water-soluble vitamins are abosorbed into the portal blood through the portal vein from the GI tract;
  • They are NOT STORED except in a pool of cell in their binding enzymes and transport proteins and excesses excreted in urine;
  • But, B12 can remain for long periods
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10
Q

How are the recommendations for vitamins provided?

A
  • Established EARs from biological markers and then derived RDAs;
  • When insufficient data for EAR, AI is provided based on observation
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11
Q

What is Vitamin C?

A
  • 6-carbon compound;
  • L-isomer is ACTIVE:
  • NOT called vit. C in mammals, but ASCORBIC ACID or ASCORBATE
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12
Q

What causes the human inability to synthesize Vitamin C?

A
  • Lack of the last enzyme in the synthetic pathway = Glucolactone oxidase;
  • Also, Primates, fruit bats, guinea pigs, and some birds cannot SYNTHESIZE the L-ascorbic acid
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13
Q

What is Scurvy?

A
  • Vitamin C deficiency disease;
  • Body pools below 300 mg and plasma vitamin C below 0.2 mg/dl;
  • “spitting out teeth below ship’s deck”;
  • Fatal if untreated;
  • Can be prevented with intakes as little as 10mg Vit. C per day = RARE to develop
  • Symptoms are due to compromised COLLAGEN structure which causes weakening of blood vessels, connective tissues and bone
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14
Q

When was Vitamin C discovered?

A

-Isolated in 1928 and its structure determined in 1933;
-Szent-Györgyi (1928) and King (1932) are both given credit for the co-discovery;
Haworth determined its structure
-Szent-Györgyi and Haworth won Nobel prize in 1937

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15
Q

What are the food sources of Vitamin C?

A
  • Present in many fruits & vegetables;

- CITRUS products most often given credit as the best source

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16
Q

What are the types of Vitamin C supplements?

A
  • Free ascorbic acid;
  • Calcium ascorbate;
  • Sodium ascorbate;
  • Ascorbyl palmitate;
  • Often see rose hips (seed capsule on roses) on labels of vitamin C supplements
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17
Q

What DIGESTION of Vitamin C takes place?

A

-NO DIGESTION required for absorption into intestinal cells

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18
Q

How is Vitamin C absorbed?

A
  • Absorption by SVCT1 (higher capacity) & SVCT2 that are sodium co-transporters
  • Sodium-dependent Vitamin C Transporter;
  • REDUCTION prior to absorption so absorbed as ascorbate by SVCTs
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19
Q

How is the OXIDIZED form of Vitamin C absorbed?

A
  • Dehydroascorbate absorbed via GLUT1 and GLUT3 transporters;
  • Dehydroascorbate is converted in intestinal and other cells to ASCORBATE;
  • Tissue Cells have SCVT1 for ascorbate
  • SVCT2 present in most tissues except skeletal muscle and lungs
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20
Q

What cells lack the SVCT2 for Vitamin C?

A
  • Red blood cells;
  • Los SVCT proteins during maturation;
  • “SVCT2 knockout” animals genetically engineered to lack this functional gene, die shortly after birth, suggesting that SVCT2-mediated vitamin C transport is necessary for life
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21
Q

What is the absorption rate for Vitamin C?

A

-Usual intakes are 30-180 mg/day and absorbed at 70 to 90%, respectively;
-ABSORPTION decreases with higher intakes =
16% at intakes ~12 g vs. 98% at low intakes < 20 mg

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22
Q

What is the main regulator for Vitamin C absorption?

A
  • Intake!!;
  • At HIGH intakes will absorb much less because the excess not needed by the body will be excreted;
  • Water-soluble vitamins are not stored!;
  • At LOW intakes absorption will be very high so they body will utilize ALL that is consumed
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23
Q

When does Simple Diffusion of Vitamin C occur?

A
  • At high amounts of vitamin C throughout stomach and small intestine → Occurs through anion channels
  • Diffuses through anionic channels into blood and exists as FREE vitamin in blood
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24
Q

Where is the greatest concentration of Vitamin C?

A
  • Tissues have GREATER amounts than blood;
  • Maximal vitamin C pool is 2g
  • Highest concentrations in ADRENAL and PITUITARY GLANDS
  • High levels also in white blood cells, eyes and brain;
  • Assume in free form in tissues and compartmentalized for reactions
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25
Q

What is needed to achieve the Maximized Body Pool for Vitamin C?

A
  • Estimated need 100 to 200 mg ingestion of vitamin C per day;
  • Gives a plasma concentration of 1.0 mg/dl
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26
Q

What is the mechanism for the interconversion of ascorbic acid and dehydroascorbic acid?

A
  • During oxidation of ascorbic acid, free radical ascorbyl radical forms, but has a short half-life;
  • Oxidation of the radical forms of Vitamin C occurs;
  • Dehydroascorbic acid can be reduced to ascorbic acid with hydrogens provided by reduced Glutathione (GSH)
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27
Q

What is Glutathione?

A
  • Antioxidant that prevents free radicals;

- Tripeptide of Cysteine, Glutamate, and Glycine

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28
Q

What reactions require Vitamin C (Ascorbate)?

A

[Functions in a number of Hydroxylation Reactions]

  • Collagen synthesis
  • Carnitine synthesis
  • Tyrosine synthesis and catabolism
  • Neurotransmitter synthesis
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29
Q

What are the main COFACTORS that Vitamin C acts on?

A

-COPPER or IRON cofactor;

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30
Q

What is the role of vitamin C in these reactions?

A
  • ANTIOXIDANT;
  • Cofactor loses and electron and becomes oxidized to allow the enzymatic reaction to occur → ;Cu3+ → Cu2+] [Fe3+ → Fe2+];
  • OXIDIZED form is a damaging FREE RADICAL
  • Vitamin C resupplies the lost reaction to reduce the cofactor for function in future reactions and prevention of radicals = becomes OXIDIZED
  • Vitamin C keeps the cofactor in the reduced state so the enzyme can function;
  • Cofactor GAINs electrons and is no longer damaging
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31
Q

What other components can Vitamin C REDUCE?

A
  • Tyrosine synthesis & catabolism;
  • Neurotransmitter synthesis (Norepinephrine, Serotonin, Other peptide hormones)
  • Collagen synthesis
  • Carnitine synthesis
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32
Q

How is Phenylalanine converted to Tyrosine with the help of Vitamin C?

A

Vitamin C (ascorbate) functions as the reducing agent (BECOMES oxidized) =

  • Converts oxidize Copper atoms (Cu2+) to reduced Cu3+ AND;
  • Converts oxidized iron (Fe2+) to reduced Fe3+
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33
Q

What is Alkaptonuria?

A
  • Defects in the enzyme Homogentistate dioxygenase = involved in Phenyalanine to Tyrosine metabolism involving Vitamin C;
  • Leads to accumulation of homogentisate in the body with painful joints and secretion of it in urine and the compound turns black with exposure to air
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34
Q

Defects in what enzyme cause PKU?[

Phenylalanine to Tyrosine metabolism]

A

Phenylalanine monooxygenase -Fe

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35
Q

Defect in what enzyme cause Tyrosinemia type II?

[Phenylalanine to Tyrosine metabolism]

A

Aminotransferase-PLP

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36
Q

What is Amidation of peptides?

A
  • ADDITION of an amide group to the end of a polypeptide chain =
  • In a first reaction step the GLYCINE is oxidized to form alpha-hydroxy-glycine;
  • The oxidized glycine cleaves into the C-terminally amidated peptide and an N-glyoxylated peptide (Glyoxylate);
  • C-terminal amidation is essential to the biological activity of many neuropeptides and hormones
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37
Q

What is Vitamin C’s role if Amidation of peptides with C-terminal Glycine?

A
  • Converts the oxidized copper and back to its reduced form Cu1+;
  • Ascorbate (Vit C) oxidized back to Dehydroascorbate = LOST an electron
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38
Q

What are some of the neurotransmitters that require Vitamin C for synthesis through AMIDATION?

A
  • Bombesin (gastrin-releasing peptide [GRP];
  • Calcitonin;
  • Cholecystokinin (CCK);
  • Thyrotropin;
  • Corticotropin-releasing factor;
  • Oxytocin;
  • Vasopressin
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39
Q

What is Collagen?

A

Structural protein in skin, bones, tendons, cartilage, dentine, basement membrane lining capillaries, and maintenance of scar tissue;
-Mammals typically have more than 30 variants each with a different structure and function

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40
Q

How are the molecules of collagen cross-linked together?

A
  • Vitamin C-dependent hydroxylations of proline and lysine occur post-translationally after amino acid is in the protein forming the TRIPLE HELIX;
  • Hydroxylation adds an (-OH) into the molecule to form a new bond;
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41
Q

What are Dioxygenases?

A

–Enzyme which catalyzes the incorporation of both atoms of molecular oxygen into substrates using a variety of reaction mechanisms

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42
Q

What are the specific dioxygenase amino acids of Collagen?

A

-Two proline hydroxylases (prolyl 4-hydroxylase and prolyl 3-hydroxylase) that are dioxygenases;
-A lysine hydroxylase (lysyl hydroxylase) that is also a dioxygenase
= These hydroxylated amino acids provide more STRENGTH to the collagen

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43
Q

What copper dependent enzyme can also promote collagen cross-linking?

A

-LYSYL OXIDASE can oxidize the lysine and hydroxylysyl residues to promote cross-linking

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44
Q

How does Vitamin C facilitate collagen cross-linking?

A
  • Ascorbate (Vit. C) converts the oxidized IRON bac to reduced Fe3+ in the enzymes Lysyl hydroxylase and propyl hydroxylate;
  • TWO atoms of dioxygen are REDUCED to ONE HYDROXYL group and one H2O molecule by the concomitant (following) oxidation of NAD(P)H;
  • The enzymes add ONE atom of Oxygen in the hydroxyl group of the product and the other in Succinate
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45
Q

What are Monooxygenases?

A

-Enzymes that incorporate ONE hydroxyl group into substrates in many metabolic pathways

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46
Q

What are the genetic defects that can occur in collagen structure?

A

-Osteogenesis imperfecta is abnormal bone formation in babies
-Ehlers-Danlos syndrome is characterized by loose joints
= Replacement of a single GLYCINE by larger amino acids in a different location for each disorder → Glycine is the SMALLEST AA;
-Both can be lethal

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47
Q

What is the triple coil of collagen composed of?

A
  • 3 distinct alpha-chains;

- Alpha-chains are NOT alpha-helix, and the structure is very different

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48
Q

Differences in Alpha HELIX and Alpha CHAINS

A
  • Alpha HELIX is RIGHT handed, but the Alpha CHAINS are LEFT handed
  • Alpha helix has 3.6 amino acids per turn
  • Alpha chain has 3 amino acids per turn
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49
Q

How is collagen coiled?

A
  • Triple helix of 3 alpha-chains is a coiled coil and is considered a super-helical structure as the three chains are super-twisted about each other in a RIGHT handed coil;
  • Opposite in sense to the left handed helix of the α chains;
  • LEFT handed alpha-chains make up the full RIGHT handed SUPER-COIL
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50
Q

What is Carnitine?

A
  • Non-protein nitrogen-containing compound;
  • Involved with transport of long-chain fatty acids into mitochondria for β-oxidation;
  • Made from LYSINE that has been methylated by S-adenosylmethionine =;
  • Vitamin C reduces the Iron in the process
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51
Q

What other reactions might require vitamin C?

A

-Microsomal metabolism;
-In the Reticuloendothelial System, also called Macrophage System
= Include hydroxylation reactions that are catalyzed by monooxygenases that require reducing agents and vitamin C may play a role

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52
Q

What are microsomes?

A
  • in the smooth ER membranes;

- Degrade hormones, modulate cholesterol, degrade xenobiotics (drugs, carcinogens, additives, pollutants, etc)

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53
Q

What is the Reticuloenothelial or Macrophage System?

A
  • Body’s defense mechanism;
  • Phagocytic cells that destroy bacteria, foreign substances, and worn out/abnormal body cells;
  • Derived from precursors in the bone marrow;
  • Become monocytes in the bloodstream or enter tissues and become macrophages
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54
Q

What is an Antioxidant?

A
  • Vit. C can be a generic antioxidant in aqueous solution (blood, in cells);
  • Prevents oxidation of other molecules (Leads to free radicals) by REDUCING them;
  • Can REDUCE other reducing agents when they are oxidized and vice-versa;
  • Once used, most tissues have REDUCTASE to reform ascorbate
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55
Q

What other Reducing Agents can Vitamin C reduce?

A
  • It can REDUCE vitamin E at the aqueous:lipid interface;

- It can REDUCE free radicals and reactive species before they damage DNA, PUFA, phospholipids and proteins in cells

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56
Q

Does Vitamin C show any Pro-Oxidant activity?

A
  • Pro-oxidant only IN VITRO (lab) and at very high non-physiological concentrations;
  • Used to think high doses released iron stores leading to oxidation, but now state no.
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57
Q

In what other system might Vitamin C play a role?

A
  • Collagen gene expression;
  • Synthesis of bone matrix, proteoglycans, and elastin;
  • Regulation of cellular nucleotide (cAMP and cGMP) concentrations
  • Immune functions, including complement synthesis
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58
Q

What is the relationship between Vitamin C and colds?

A
  • High doses NO effect in most studies, but a few studies show a decrease in duration of symptoms;
  • Does enhance many immune cell functions and destroys HISTAMINE that causes many of a cold’s symptoms
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59
Q

What is the relationship between Vitamin C and cancer?

A
  • Makes sense that antioxidant would prevent cancer;
  • Some epidemiological studies indicate protection against cancers of the oral cavity, pharynx, esophagus and stomach;
  • Fruit and vegetable consumption is correlated with reduced cancers;
  • But a lot of studies show no effect
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60
Q

What is the relationship between Vitamin C and CVD?

A
  • Epidemiological studies with fruits and vegetables and vitamin C suggest a protective;
  • Intervention studies with vitamin C and other antioxidants DO NOT support the epidemiological studies;
  • Megadose supplements of antioxidants INCREASE mortality and morbidity risks
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61
Q

What is the relationship between Vitamin C and eye health?

A

-Studies show benefit against cataracts and age-related macular degeneration with consumption of mutivitamin

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62
Q

What is the INTERACTION between Vitamin C and Iron?

A

-Enhances non-heme iron absorption

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63
Q

How much accumulation of ascorbate (vit. C) occurs within the body?

A
  • Dietary doses;

- Until the plasma levels reach the renal resorption threshold, which is about 1.5 mg/dL in men and 1.3 mg/dL in women

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64
Q

What happens once Ascorbate concentrations in the plasma exceed the renal absorption threshold?

A
  • Point of body saturation;
  • Rapidly excreted in the urine with a half-life of about 30 minutes;
  • At intakes about 500 mg, ALL vitamin C is usually excreted (assume above renal threshold)
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65
Q

What happens when Ascorbate concentrations in the plasma are below the threshold?

A
  • Actively retained by the kidneys;
  • Excretion half-life for the remainder of the vitamin C store in the body thus INCREASES greatly, with the half-life lengthening as the body stores are depleted;
  • Half-life rises until it is as long as 83 days by the onset of the first symptoms of Scurvy.
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66
Q

What are the other Urinary metabolites that accompany Vitamin C excretion?

A
  • 2-O-methyl-ascorbate, ascorbate-2-sulfate, and 2-ketoascorbitol;
  • Excreted as CO2 and water
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67
Q

What is the RDA (bio marker) for Vitamin C?

A
  • Men = 90 mg
  • Women = 75 mg
  • Pregnancy = 100 mg; Lactation = 120 mg;
    • 35 mg for SMOKERS and this was first recognized as a greater need in 1989 RDA → Increased RDA due to the extra oxidative stress from cigarette smoking toxins and thus generally have lower blood levels of Vit. C
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68
Q

What is the RDA for Vitamin C based upon?

A

-Nearly maximizing tissue concentrations and minimizing urinary excretion of the vitamin;
Amount needed to maintain NEUTROPHIL saturation (AKA White Blood Cells) with minimal urinary excretion;
-Some in the past before the year 2000 have argued for an RDA of 200 mg/day as that would be the amount would consume if met the recommendation for fruits and vegetables

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69
Q

What is the UL and toxicity for Vitamin C?

A
  • 2 g, based on osmotic diarrhea (metabolized by bacteria) and GI pain;
  • Rebound scurvy not substantiated;
  • Excess in urine can interfere with urine glucose test, interfere with detection of blood in urine and feces
  • People prone to a couple of types of kidney stones should avoid large doses of vitamin C
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70
Q

How do Plasma and Serum Concentrations indicate Vit. C nutritional status?

A
  • Concentrations respond to changes in dietary intake and most convenient assay;
  • Quick and easy indicator; daily lab use and diagnosis
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71
Q

How do White Blood Cells indicate Vit. C nutritional status?

A
  • Better reflect body stores, but assay more difficult for routine use;
  • More indicative, but also too difficult for immediate, general diagnosis
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72
Q

When is there a Vitamin C deficiency?

A
  • DEFICIENT = <0.2 mg/dl, tissue saturation 1.0 mg/dl

- Recommended intakes result in a range of 0.6 to 0.8 mg/dl

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73
Q

What is Thiamin?

A
  • First B vitamin identified;

- B1

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74
Q

What is BeriBeri?

“Weakness”

A
  • Thiamine deficiency disease present for over 1000 years in East Asia occurred where white rice was the staple of the diet;
  • Thought to be an infectious disease until determined chickens fed white polished rice developed the disease and got better when fed brown rice;
  • Polished rice is essentially just starch
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75
Q

Who were the scientists that discovered Thiamin?

A
  • NEED by Dutchman C. Eijkman (1800s) – Discovered that chickens fed a diet consisting of polished (removal of outer layer) rice developed neuorlogical problems;
  • ISOLATED from RICE BRAN in 1912 by Casmir Funk
  • STRUCTURE by R. Williams about the mid 1930s
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76
Q

What are the food sources of Thiamin?

A
  • Enriched grains, whole grains, legumes, nuts and seeds;
  • Found in yeast, wheat germ and soy milk;
  • In food is sensitive to heat, oxygen and low-acid conditions (stable in acid and unstable in alkaline)
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77
Q

What are the ANTI-Thiamine enzyme or binding factors in foods?

A
  • In raw seafood (cooking destroys);

- Binding factors block absorption = Polyhydroxyphenols

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78
Q

How do Polyhydroxyphenols block Thiamin?

A
  • Tannic and caffeic acid are thermostable and INACTIVATE thiamin by OXIDATION;
  • Reducing compounds protect from oxidation
  • Divalent minerals accelerate oxidation (valence of two and can form two bonds)
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79
Q

What constitutes the structure of Thiamin?

A

-Pyrimidine ring +
-Thiazole ring
(Linked with a Methylene bridge)

80
Q

What are the forms of Thiamin found in FOOD?

A
  • Plants = NONPHSOPHORYLATED or free form;

- Animals = PHOSPHORYLATED primarily as thiamin diphosphate (TDP) in mucosal cells; AKA: Thiamine Pyrophosphate (TPP)

81
Q

What are the forms of Thiamin supplements?

A
  • Thiamin hydrochloride or

- Thiamin mononitrate

82
Q

What is happens to Thiamin initially for absorption?

A
  • Intestinal PHOSPHATASES hydrolyze the phosphate off the thiamin PRIOR to absorption;
  • Removal of –PO4 allows for absorption;
  • Primarily in the JEJUNUM with small amounts absorbed in the other two small intestine sections as free thiamin (FREE thiamine is simply absorbed)
83
Q

How is Thiamin absorbed depending on concentration?

A
  • High dietary levels = absorbed by diffusion;
  • Low dietary levels = absorption is active and involves sodium-dependent carriers;
  • But may not involve sodium, but rather hydrogen ion antiport (EXCHANGE thiamine for H+)
84
Q

What are the Thiamin carriers?

A

ThTr1 & ThTr2;

  • Defects in gene for ThTr1 results in thiamin DEFICIENCY;
  • BUT ThTr2 “picks up the slack” with ThTr1 KO mice;
  • Both of these saturable and in many tissues
85
Q

How is Thiamin actively transported to the blood?

A
  • Crosses basolateral membrane into blood via active transport by hydrogen antiport;
  • Ethanol (alcohol) interferes with this active transport into the blood;
  • Alcohol inhibits the expression of ThThr1 and ThTr2 and therefore inhibits Thiamin absorption
86
Q

What is the form of most BLOOD thiamin?

A
  • PLASMA has free thiamin, bound to albumin, or TMP;
  • ~90% of blood thiamin is WITHIN blood CELLS as TDP (or TPP), which was formed within the cell, with smaller amounts of TMP;
  • Transport into red blood cells by FACILITATED DIFFUSION as FREE thiamin bound to Albumin or TMP = only fonts that can enter cels
  • (into OTHER tissues requires energy);
87
Q

How much Thiamin is found within the body?

A

~30 mg of Thiamin;

  • Small concentrations stored in liver, muscles, heart, kidneys and brain;
  • Muscles contain about HALF the body’s thiamin; -Thiamin half-life = 10-20 days
88
Q

What is the MAIN form of Thiamin found within the human body?

A
  • ~80% of thiamin in body is TDP (TPP) = Thiamin Pyrophosphate;
  • Several interconvertible forms = free, TMP, TDP (TPP), and TTP;
  • ~10% in the body tissues as TTP
89
Q

What happens to Thiamin when it is absorbed into the Portal blood?

A

-After absorption into PORTAL blood, thiamin is taken up by the LIVER and converted to its TDP COENZYME form

90
Q

What are the 3 main functions of Thiamin?

A
  1. Energy transformation (coenzyme);
  2. Synthesis of pentoses and nicotinamide adenine dinucleotide phosphate (NADPH) (coenzyme);
  3. Nerve conduction (NOT a coenzyme role)
91
Q

What is the Coenzyme form of Thiamin?

A

-TDP (or TPP);
Plays key role in oxidative decarboxylation reactions (SAME MECH.):
-Pyruvate to acetyl CoA
-α-ketoglutarate to succinyl CoA
-Conversion of the three branched-chain amino acids isoleucine, leucine and valine

92
Q

How does TPP work as a coenzyme in these reactions?

A

-TPP catalyses the reversible cleavage of a substrate compound at a carbon-carbon bond connecting a carbonyl group to an adjacent reactive group (usually a carboxylic acid or an alcohol)

93
Q

Steps of the TPP Mechanism

A
  1. Reactive carbon 2 atom of the thiazole ring ionizes (loses H) to form a carbanion (negatively charged Carbon);
  2. Carbanion then attacks the carbonyl group of pyruvate, alpha-KG, etc;
  3. Attacking carbanion of the TPP at the carbonyl creates new attached compound
94
Q

What is the Pentose Phosphate Pathway?

A
  • ALTERNATIVE route for GLUCOSE;
  • Occurs in the LIVER and CYTOSOL of cells;
  • Does NOT generate ATP;
  • Forms of NADPH for SYNTHESIS of fatty acids and steroids;
  • Synthesis of RIBOSE for nucleotide and nucleic acid formation
95
Q

What is similar between Glycolysis and the Pentose Phosphate Pathway?

A
  • More complex than glycolysis and the reactions also occur in the CYTOSOL;
  • As in glycolysis there is DEHYDROGENATION (remove an H and electrons), but NADP+ instead of NAD+ is the hydrogen and electron acceptor
96
Q

What is the FIRST phase of the Pentose Phosphate Pathway?

A
  1. OXIDATIVE nonreversible phase =
    •One run of OXIDATIVE phase:
    -3C6 + 6NADP+ → 3C5 + 3CO2 + 6NADPH + H+
    -[Glucose 6-Phosphate → Ribulose 5-Phosphate]
97
Q

What is the SECOND phase of the Pentose Phosphate Pathway?

A
  1. a NONOXIDATIVE reversible phase =
    One run of NONOXIDATIVE phase:
    -3C5 → 2C6 + C3 (or ½ C6)
    -[Ribulose 5-Phosphate → Glucose 6-Phosphate + Glyceraldehyde 3-Phosphate]
98
Q

What is the overall process of the Pentose Phosphate Pathway?

A

Often shown as X2=

  • 6C6 + 12NADP+ 4C6 + 2C3 + 6CO2 + 12NADPH + H+;
  • Then: 2C3 → C6
  • *For oxidation of one glucose resulting in 5C6
99
Q

Where are the roles of Thiamin in the NONoxidative phase of the Pentose Phosphate Path?

A

Breakdown into scramble gives:
1. 2C5 → C7 + C3 – transketolase (thiamin = (moving a C2)
2. C7 + C3 → C4 + C6 – transaldolase = (moving a C3)
3. C4 + C5 → C6 + C3 – transketolase (thiamin) = (moving a C2 )
= 3C5 → 2C6 + C3

100
Q

How does TPP (thiamin pyrophosphate) catalyze the Pentose Phosphate Path?

A

Tranksketolate = enzyme;
TPP = cofactor;
In the NONoxidative phase:
-TPP accepts a 2-carbon fragment from a 5-carbon ketose;
-Then transfers this fragment to a 5-carbon aldose to form a 7-carbon ketose

101
Q

How does Thiamin affects nerve cells?

A

NOT a COENZYME here;

  • Electrical activity of nerve cells is changed when antagonists (promoters) of thiamin are used;
  • Thiamin itself may be involved in nerve impulse transmission by regulating sodium channels and in phosphorylation of proteins;
  • TPP appears to be released when nerve impulses are stimulated
102
Q

How Thiamin EXCRETED?

A
  • EXCESS thiamin in various forms can be excreted INTACT or CATABOLIZED;
  • Initially thiamin is BROKEN into pyrimidine and thiazole components
103
Q

What happens to the pyrimidine and thiazole components from broken Thiamin?

A
  • The two rings are further catabolized;
  • Generates 20 or more metabolites;
  • EX: 4-methyl thiazole 5-acetic acid and 2-methyl 4-amino 5-pyrimidine carboxylic acid
104
Q

What is the RDA for Thiamin?

A
  • Men = 1.2 mg/day adult
  • Women = 1.1 mg/day
  • Pregnancy = 1.4 mg/day;
  • Lactation = 1.5 mg/day
105
Q

How is Thiamin status tested?

A
  • Add thiamin to HEMOLYZED whole blood or measure thiamin in blood or urine;
  • Hemolyzed blood – erythrocytes (red blood cells) have been ruptured, releasing their contents;
  • Erythrocyte Thiamin deficiency = >1.25;
  • Urine thiamin deficiency = <27
106
Q

What is Wernicke’s Syndrome?

A
  • Thiamin deficiency associated with ALCOHOLISM:

- Neuropsychological complication;

107
Q

What are the 3 problems alcoholics have with Thiamin?

A
  1. Decreased food consumption = not enough dietary sources;
  2. Liver damage decreases TDP formation = increased requirements of the vitamin, which then impairs TDP formation in the liver and ultimately impairs vitamin use
  3. Decreased absorption = alcohol inhibits the expression of the carriers ThTr1 and ThTr2 and therefore inhibits Thiamin absorption
108
Q

What other conditions have been linked to Thiamin deficiency?

A
  • Congestive heart failure that may be due to diuretic use causing increased thiamin excretion and may be low intake;
  • Other conditions that have resulted in thiamin deficiency are with TPN without thiamin included and excess glucose infusion
109
Q

Is there a UL for Thiamin?

A
  • No UL has been established
  • 500 mg ingested daily for a month did not have any problems
  • This level of supplementation helps those with maple syrup urine disease → also consume low protein helps with this disease
  • Maple Syrup Urine disease – can’t fully metabolize BCAA’s
110
Q

How can Thiamin supplementation be used a drug treatment?

A

-Helps patients with LACTIC ACIDOSIS by increasing pyruvate dehydrogenase activity and increases the conversion of pyruvate to acetyl-CoA;
-Thiamin is the coenzyme to this reaction → It decreases the conversion of pyruvate to lactic acid as more pyruvate is decarboxylated to acetyl-CoA to enter the TCA cycle;
AND
-Also a thiamin-responsive megaloblastic anemia that is treatable with high supplementation

111
Q

How was Riboflavin (B2) discovered?

A

1917, originally called Vitamin G;

  • Gyorgy showed that vitamin B2 cured egg white injury;
  • Then in 1933, Gyorgy worked with Warner-Jauregg in Kuhn’s lab to feed thiamin-free extracts of yeast, liver, or rice bran and supplemented with thiamin – they prevented growth failure;
  • 1934, Kuhn’s group identified the structure
112
Q

What is the structure of Riboflavin?

A

-“Ribo” comes from ribose-like SIDE-CHAIN and “flavus” means yellow in Latin;
-Riboflavin main structure = Ribitol + Flavin
oFMN (coenzyme) = ADD a phosphate group
oFAD (coenzyme) = ADD a pyrophosphate + AMP

113
Q

What is the main chemical characteristic of Riboflavin?

A
  • Riboflavin and its conenzymes are particularly ALKALI (basic) and acid sensitive in the presence of LIGHT;
  • DESTROYED BY LIGHT → When purified activity would be lost because of room light if acidic or alkaline conditions
114
Q

What are the FOOD sources of Riboflavin?

A
  • Animal foods are GOOD with MIlk being the MOST;
  • Green veggies are GOOD;
  • Fruit and cereals are MINOR
115
Q

What is the FORM of Riboflavin in foods?

A
  • Milk, eggs, and enriched breads and cereals is either in FREE form or FMN or FAD or bound to protein;
  • In most other foods, riboflavin is found as FMN and FAD
116
Q

What is the first step of Riboflavin digestion?

A
  • HCl in stomach and enzymatic hydrolysis of the proteins frees the riboflavin from the protein attachments for activity of small intestine enzymes;
  • FAD (FAD Pyrophosphate) → FMN (FMN Phosphatase) → Riboflavin
117
Q

What can happen when Riboflavin is digested with protein?

A
  • Can result in histidine or cysteine BOUND to riboflavin as FAD or FMN;
  • This form is either NOT ABSORBED or if absorbed is EXCRETED in the urine
118
Q

What factors affect Riboflavin digestion/absorption?

A
  • Animal sources better released in digestion and absorbed;
  • Divalent metals (2 valence electrons) bind to riboflavin and FMN;
  • Alcohol impairs absorption
119
Q

How is Riboflavin absorbed after digestion?

A
  • FREE riboflavin is absorbed AFTER FAD and FMN are produced by actions of enzymes → HCl in the stomach
  • Absorption is by a saturable, energy-dependent CARRIER mechanism in the proximal (beginning) small intestine;
  • LARGE amounts can be absorbed by DIFFUSION (No carrier);
  • ~95% of food riboflavin absorbed when intake is up to 25 mg
120
Q

What is the carrier for Riboflavin?

A
  • Riboflavin transporter 2 (RFT2);

- Carriers in proximal small intestine appear to be SODIUM INDEPENDENT, but do require energy!;

121
Q

What are the methods for absorption of Riboflavin into CELLS?

A
  1. Diffusion or molecular penetration → Fat soluble
  2. Diffusion of water via Osmosis to equalize solute concentrations
  3. Facilitated diffusion through protein carrier → Fructose
  4. Glucose and Amino acids → Cotransport
122
Q

What are the forms of PASSIVE absorption or diffusion (no energy)?

A
  1. Simple - net movement from high to low conc.
  2. Facilitated - high to low conc. through transport protein
  3. Filtration - water and solute movement due to Hydrostatic Pressure
  4. Osmosis - net movement of water through semi-permiable membrane from high to low water potential
123
Q

What happens to Riboflavin once absorbed into CELLS?

A
  • ABSORBED riboflavin is converted back to FMN in the intestinal cells;
  • Then again back to riboflavin for leaving the cell and entering the blood
  • Riboflavin (GI) → FMN (cells) → Riboflavin (blood – carried by Albumin)
124
Q

How is Riboflavin transported in the BLOOD?

A
  • Transported by several proteins, mostly ALBUMIN;
  • Enters cells by riboflavin binding protein (some regulated by calcium/calmodulin)
  • DIFFUSION occurs if blood levels are HIGH → Moves from high levels in the blood to lower levels within the cells WITHOUT energy
125
Q

How is Riboflavin converted to FMN

A
  • in LIVER;
  • Flavokinase converts riboflavin to FMN;
  • Energy requiring ;
  • Flavokinase is increased by ACTH, aldosterone, and thyroid hormones
126
Q

How is FMN converted to FAD?

A

FAD synthetase converts FMN to FAD ;

  • Liver, kidney and heart have greatest amounts;
  • FAD predominates in TISSUES, but have both FMN and FAD
127
Q

How do FMN and FAD become flavoproteins?

A
  • FMN and FAD attach to APOPROTEINS to become flavoproteins that are enzymes involved in oxidation/reduction reactions;
  • Apoproteins – the protein part of an enzyme WITHOUT its characteristic prosthetic group → FMN/FAD are the prosthetic groups
128
Q

What are the FUNCTIONS of Riboflavin?

A
  • Plays a role in which hydrogen peroxide is produced from activated white blood cells;
  • Major role in OXIDATION-REDUCTION reactions, especially Oxidative Decarboxylation
129
Q

What is Oxidative-Decarboxylation?

A

oxidation reactions in which a carboxylate group is removed, forming CO2

130
Q

What is the role of FAD (riboflavin) in the electron transport chain?

A
  • Coenzyme to energy production and oxidative decarboxylation reactions!!;
  • Accepts 2 hydrogens in the TCA cycle becoming FADH2;
  • It then donates a pair of its electrons to carriers that enter the ETC to produce energy
131
Q

What is the role of FAD (riboflavin) in oxidative decarboxylation of Pyruvate?

A
  • Pyruvate dehydrogenase complex reaction;
  • FAD becomes reduces to FADH2 to accept electrons as pyruvate bind to acetyl-CoA;
  • FADH2 is then oxidized by NAD+ and the electrons are transferred to the ETC
132
Q

Where is the role of Riboflavin in the TCA cycle?

A
  • Oxidative decarboxylation of alpha-ketoglutarate.
  • The decarboxylation and dehydrogenation of alpha- Ketoglutarate is mechanistically identical to to the pyruvate dehydrogenase reaction.
133
Q

What is the role of FAD if Fatty Acid Oxidation?

A
  • Fatty acyl dehydrogenase reaction with “Fatty acid Oxidase”;
  • Performs the Acetyl-CoA dehydrogenase reaction and by conversion from FAD to FADH2 by dehydrogenation of Acetyl-CoA;
  • This reduced FADH2 then goes to the ETC to use the electrons for energy
134
Q

What is the Sphingagine Oxidase rxn that requires FAD?

A
  • Carries out SPHINOGSINE synthesis ;

- Sphingosine = primary part of sphingolipids, a class of cell membrane lipids

135
Q

What is the Xanthine Oxidase rxn that requires FAD?

A

Involved in purine catabolism in liver;

  • Hypoxanthine to xanthine to uric acid, delivers electrons and hydrogen directly to oxygen producing H2O2;
  • contains iron and molybdenum
136
Q

What is the Aldehyde Oxidase rxn that requires FAD?

A

EXs:

  • Converts pyridoxal (vitamin B6) to pyridoxic acid for excretion;
  • Retinal to retinoic acid (one of the active forms of vitamin A)
  • Also forms H2O2
137
Q

What is the Pyridoxine Phosphate Oxidase rxn that requires FAD?

A

-FMN is used to convert PMP and PNP to PLP = the coenzyme form of vitamin B6

138
Q

How is FAD needed in folate metabolism and utilization?

A
  • Needed for synthesis of 5-methyl tetrahydrofolate (THF);
  • High supplemental doses of FOLIC ACID can produce dihydrofolate (DHF);
  • DHF is a derivative which is converted to tetrahydrofolic acid by dihydrofolate reductase
139
Q

How can someone overcome low functioning MTHFR of folate?

A

MASS ACTION can overcome MTHFR low function converting 5,10 methylene THF to 5-methyl THF or low vitamin B12 converting 5-methyl THF to THF

140
Q

What NEUROTRANSMITTERS require FAD?

A

-Dopamine and other amines, tyramine and histamine, require the enzyme MONOAMINE OXIDASE which requires FAD

141
Q

How does FAD regenerate Glutathione?

A
  • Glutathione is an antioxidant that becomes OXIDIZED to prevent free radicals;
  • Reduction of the oxidized form of glutathione (GSSG) to the reduced form (2GSH) is dependent on FAD-dependent glutathione reductase;
  • One method to assess riboflavin status
142
Q

How do Erol and sulfhydryl oxidases use FAD?

A
  • FAD-dependent;

- Form DISULFIDE BONDS (oxidation) and leads to protein folding of SECRETORY proteins

143
Q

How do Thiredoxin reductase and glutaredoxin reductases use FAD?

A
  • Transfer reducing equivalents from NADPH + H+ through FAD to reduce DISULFIDE BONDS (oxidation) within oxidized form of thioredoxin or glutaredoxin;
  • Thioredoxin or glutaredoxin then provide electrons and hydrogens (reduces) to ribonucleotide reductase for conversion of ribonucleotides to deoxyribonucleotides
144
Q

How does L-amino Oxidase use FMN?

A

-Dehydrogenation of L-amino acids to imino acids

145
Q

What is an IMINO Acid?

A
  • Any molecule that contains BOTH imino (>C=NH) and carboxyl (-C(=O)-OH) functional groups;
  • Amino acids containing a SECONDARY amine group are sometimes named imino acids (the only proteinogenic amino acid of this type is PROLINE)
146
Q

What is the difference between Imino Acids and IMIDIC acids?

A

Imidic Acids contain the group -C(=NH)-OH;

-NOT the same

147
Q

How is Riboflavin excreted?

A
  • Riboflavin is excreted in the urine INTACT;

- When take a vitamin pill with riboflavin get bright yellow or orangish yellow urine

148
Q

What is the RDA for Riboflavin?

A
  • Men = 1.3 mg/day
  • Women = 1.1 mg/day;
  • Amounts greater than 120 mcg/day or 80 mcg/g creatinine in urine is considered a marker of ADEQUATE INTAKE;
  • NO UL
  • 400mg used to tread migraines
149
Q

How is nutritional adequacy of Riboflavin tested?

A
  • Activity of red blood cell glutathione reductase WITH and WITHOUT added FAD is used for testing adequacy
  • 1.4 is DEFICIENT
150
Q

What is the deficiency of Riboflavin?

A

ARIBOFLAVINOSIS;

  • Not a technical deficiency disease;
  • Results in problems with tongue, lips, mouth, dermatitis, anemia, and peripheral nerve dysfunction
151
Q

What occurs in people with C677>T MTHFR and low riboflavin?

A

-Increase HOMOCYSTEINE;
-Homocysteine – Non-protein alpha-amino acid; homologue of Cysteine containing an extra methyl bridge=
•Synthesized from methionine → Can be reused back to methionine or turned into cysteine with the help of B vitamins
•*High levels are linked to CVD → increases risk of endothelial injury which leads to vascular inflammation;
-Conversion of tryptophan to niacin is reduced or eliminated
-Coenzyme form of vitamin B6 is lower

152
Q

What is the AI and UL for Choline?

A
  • Historically NONESSENTIAL;
  • Men = 550 mg/day;
  • Women = 425 mg/day;
  • UL is 3.5 g/day – hypotension, sweating, diarrhea, and a fishy odor;
153
Q

Choline is a PRECURSOR for….

A
  • Acetylcholine
  • Phosphatidylcholine
  • Methyl donor betaine;
  • *Found in the diet FREE or as apart of compounds
154
Q

What makes Choline possible NONESSENTIAL?

A
  • Choline is synthesized de novo by synthesis from phosphatidyl ehtanolamine and this is dependent on methionine, folate, and vitamin B12;
  • [De novo = synthesis of complex molecules from simple molecules such as sugars or amino acids]:
  • Healthy men with normal status for folate and vitamin B12 fed a choline-deficient diet develop liver damage
155
Q

How is Choline Catabolism?

A

-Functions with choline dehydrogenase (1), dimethylglycine dehydrogenase (4), and sarcosine (monomethylglycine) dehydrogenase (5) require FAD

156
Q

What are the choline related compounds or metabolites?

A
  • Betaine aldehyde;
  • Betaine;
  • Dimethylglycine;
  • Sarsosine;
  • Glycine;
  • Phosphocholine;
  • Phosphatidylcholine;
  • Sphingopmyelin;
  • Choline phospholipids
157
Q

How is Choline utilized in the body?

A
  • PANCREATIC enzymes FREE choline;
  • Choline is ABSORBED in the small intestine via transporter proteins;
  • Choline is absorbed into PORTAL blood, but any phosphatidylcholine enters the LYMPH in chylomicrons;
  • Phosphatidylcholine – phospholipids with choline incorporated as a headgroup → Lipid so MUST travel through the lymph;
  • TISSUES take up choline by a carrier mechanism and by diffusion
158
Q

What is Niacin (B3)?

A

-NIACIN is a generic descriptor for nicotinic acid (pyridine-3-carboxylic acid) and nicotinamide (nicotinic acid amide)

159
Q

When was Niacin discovered?

A
  • Nicotinic acid was isolated as a pure chemical in 1867;

- 1937 that it was demonstrated as the anti-black-tongue factor in dogs and the anti-pellagra vitamin for humans

160
Q

What was the original belief regarding Pellagra?

A
  • Thought pellagra was due to a deficiency of TRYPTOPHAN in corn even though the pathway of tryptophan to niacin had not been discovered at that time;
  • Pathway not discovered until after both forms of niacin shown to be antipellagragenic;
  • Also thought to be an Infectious disease
161
Q

What made Pellagra very common in the SE United States?

A
  • Corn was not treated with alkali as in Mexico and the niacin was NOT AVAILABLE from the corn;
  • The diet had pork fat and not high quality protein for the most part so tryptophan to niacin would be limited;
  • Early 1900s psychiatric hospitals in the Southeast were filled with patients suffering from DEMENTIA from pellagra
162
Q

Who proved pellagra was NOT an infectious disease?

A
  • Joseph Goldberger and co-workers contaminated themselves with materials from pellagra patients;
  • He was shown to be correct, he died in 1929 when pellagra epidemic was at its height
  • Epidemic ended with federal program of ENRICHMENT of grains and improved economy after World War II
163
Q

What are the 4 D’s of Pellagra?

A
  • Dermatitis;
  • Dementia;
  • Diarrhea;
  • Death
164
Q

What are the food sources of Niacin?

A
  • Fish and other animal flesh products are GOOD sources;
  • Enriched and whole grains also GOOD sources;
  • Coffee and tea contain, green vegetables and milk have LOWER amounts
165
Q

What are the forms of Niacin in animals products?

A

In animals found in coenzyme forms NAD and NADP, but with slaughter, degraded to nicotinamide

166
Q

How is Niacin found COVALENTLY bound in foods?

A
  • Niacytin is when bound to complex CARBS and ;
  • Niacinogens when bound to small PEPTIDES → these are found primarily in corn, but also in wheat and some other cereal grains;
  • Chemical treatment with ACIDS, such as lime water, FREES the niacin, otherwise only about 10% is available from corn due to stomach acid releasing some;
  • Niacin is NOT readily bioavailable from corn!
167
Q

What are the COENZYME forms of Niacin?

A

-NAD (catabolic) and NADP (anabolic)
-Oxidized forms = NAD or NAD+; NADP or NADP+
[Oxidized = LOSE electrons and become more positive!!]

168
Q

What amino acids can be used to synthesize niacin in the form of NAD?

A
  • In the LIVER, NAD can be synthesized from tryptophan, but only about 3% of metabolized tryptophan (amino acid) converted to NAD;
  • Tryptophan → NAD = makes Niacin a NONESSENTIAL Vitamin;
  • Estimated need 60 mg tryptophan to produce 1 mg NAD
169
Q

What happens to the NAD and NADP created from Tryptophan?

A

-NAD and NADP converted to nicotinamide by enzymes Glycohydrolase and Pyrophosphate

170
Q

How must NAD/NADP be digested?

A
  • Must be digested to NICOTINAMIDE for ABSORPTION;

- Pyrophosphatase REMOVES phosphate off NADP and glycohydrolase FREES nicotinamide

171
Q

How is Niacin absorbed in the small intestine?

A
  • Niacin in NORMAL concentrations in diet is absorbed by a sodium-dependent carrier by FACILITATED diffusion;
  • LARGE doses absorbed by PASSIVE diffusion
172
Q

How is Niacin found in the PLASMA?

A
  • Found primarily as NICOTINAMIDE, but some nicotinic acid can be found in plasma;
  • Some of NICOTINIC ACID is bound to PROTEINS
173
Q

How does Niacin enter CELLS?

A
  • Nicotinamide eneter by SIMPLE DIFFUSION;

- Carriers required in the KIDNEY TUBULES and RED BLOOD CELLS

174
Q

What happens to the Nicotinamide once it enters CELLS?

A
  • Converted to coenzyme forms NAD and NADP and these forms TRAP the vitamin within cells;
  • COENZYMES are the form found WITHIN the CELLS;
  • LIVER can convert NICOTINIC ACID to coenzymes
175
Q

What is the main function of NAD/NADP?

A

~200 enzymes, primarily DEHYDROGENASES that require the coenzymes NAD or NADP;
EX: glycolysis, oxidative decarboxylation of pyruvate to acetyl-CoA, oxidation of acetyl-CoA in the TCA cycle, beta-oxidation of fatty acids, and oxidation of ethanol

176
Q

How is NAD used in the catabolism of B6?

A
  • NAD required by ALDEHYDE DEHYDROGENASE for catabolism of vitamin B6 in form of pyridoxal to pyridoxic acid for EXCRETION
  • Niacin is needed to BREAKDOWN Vitamin B6 for utilization and then excretion
177
Q

What is the role of NAD as a coenzyme?

A
  • Transfer electrons and hydrogens from metabolic intermediates to the electron transport chain;
  • One H of the substrate goes to NAD to create NADH + H+;
  • CANNOT generate energy through the ETC without Niacin
178
Q

What is the ETC couple with to generate ATP?

A
  • Oxidative phosphorylation and production of ATP;

- Oxidative Phosphorylation – mitochondria released the energy found in oxidated nutrients to create ATP

179
Q

What is the function of NADPH?

A
  • REDUCING AGENT in many biosynthetic pathways such as fatty acids, cholesterol and steroid hormones → ANABOLIC coenzyme!;
  • Also proline synthesis, deoxyribonucleotide synthesis, and glutathione, vitamin C, and thioredoxin regeneration;
  • FOLATE metabolsim requires NADPH;
  • Addition of the –PO4 group allows for the reaction to run in reverse rxn and not be dependent on NAD concentrations
180
Q

What is the NONRedox role of Niacin?

A

-Post-translational modification of proteins associated with chromosomes and formation of cyclic ADP-ribose

181
Q

How do NAD and the cyclic ADP-RIbose function in the NEURONS?

A

-NAD glycohydrolases and the cyclic ADP-ribose functions as SECOND MESSENGER to control ryanodine receptors and release calcium from intracellular stores especially in neurons

182
Q

How do NAD and the cyclic ADP-RIbose function in IMMUNE RESPONSE?

A

-Transfer of mono ADP-ribose to proteins on cell surfaces for IMMUNE RESPONSE;
-ADP-ribose transfer is performed by mono ADP-ribosyl transferases (ARTs);
-There are also poly ADP-ribose polymerases (PARP) that also use NAD;
ADP-ribose transfer plays a role in DNA repair, replication and transcription, and chromatin structure

183
Q

How is Niacin RECYCLED?

A
  • NAD and NADP are DEGRADED by glycohydrolases and pyrophosphatases to nicatinamide and ADP-ribose;
  • Then can be recycled or converted to excretion products
184
Q

What is the breakdown of Niacin?

A

Breakdown = NAD/NADP → [glycohydrolases and pyrophosphates] → nicatinamide

185
Q

How is Niacin reabsorbed?

A
  • Nicotinamide and nicotinic acid are actively REABSORBDED from glomerular filtrate;
  • Glomerular filtrate – the filtrate that passes from the lumen of the glomerular capillary to the space of Bowman’s capsule at the top of the kidney
186
Q

How is Nicotinamide EXCRETED?

A

-Methylated nicotinamide is converted in the LIVER to a variety of excretion products
-Metabolites include =
•N’methyl nicotinamide (NMN) at 20 to 30%
•N’methyl 2-pyridone 5-carboxamide (2-pyridone) at 40 to 60%;
•N’methyl 4-pyridone carboxamide (4-pyridone)

187
Q

How is Nicotinic Acid EXCRETED?

A

Nicotinic acid is mainly converted to N’methyl nicotinic acid

188
Q

In what form is Niacin NOT excreted?

A

Very little of the vitamin forms themselves without catabolism are excreted → Not excreted whole

189
Q

What are Niacin Equivalents (NE)?

A
  • Recommendation for Niacin;

- Account for the 1 mg of niacin that can be produced from~60 mg of tryptophan

190
Q

What is the RDA for Niacin?

A
  • Based on the excretion of niacin metabolites in the urine: ≥1 mg/day of NMN;
  • Men = 16 mg/day
  • Women = 14 mg/day ;
  • DIET usually contains 900 mg of tryptophan or 15 NEs
191
Q

What is the UL for Niacin?

A
  • Based on flushing (vasodilatory) effects by nicotinic acid;
  • 35 mg/day from supplements and fortified foods;
  • Nicotinamide does not cause flushing but it is believed that it is covered with flushing effects by nicotinic acid;
  • Newer extended release medicines are helpful in REDUCING risks of toxicity
192
Q

How can Nicotinic Acid be used to treat hypercholesteremia (DRUG)?

A

-Large doses up to 6 g/day;
-Lowers total cholesterol, triglycerides, LDL; increases HDL;
Mechanism includes:
-Inhibition of lipolysis in adipose tissue
-Reduction of VLDL secretion by liver and this reduces LDL
-Inhibition of diacylglycerol acyltransferase in the liver for inhibition of triglyceride synthesis

193
Q

What are other actions of Nicotinic Acid?

A
  • Nicotinic acid binds to some G-protein-coupled receptors for inhibition signals;
  • Also binds to peroxisome proliferator-activated receptor gamma (PPARgamma) in macrophages and induces prostaglandin synthesis
194
Q

What are Prostaglandins?

A

-Group of lipid compounds that are derived enzymatically from fatty acids → mediators and have a variety of strong physiological effects, such as regulating the contraction and relaxation of smooth muscle tissue

195
Q

How is Niacin status assessed?

A
  • LOW excretion and DEFICIENCY =

- Urinary excretion of <0.5 mg N’ methyl nicotinamide/1 g of creatinine

Spring 2014 (22 decks)

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