ansc314 - ribo niacin B6

vitamin classifications

• fat soluble

  • A, D, E, K

• water soluble

  • ascorbic acid (C)

  • riboflavin (B2)

  • pyridoxine (B6)

  • niacin (B3)

  • thiamin (B1)

water soluble

• Ascorbic acid (C)

• Thiamin (B1)

• Riboflavin (B2)

• Niacin (B3)

• Pyrodoxine (B6)

• Pantothenic acid (B5)

• Biotin (B7, H)

• Folacin (B9)

• Cyanocobalamin (B12)

• Choline

• Inositol

riboflavin

found as one of body’s co-enzymes

• flavin mononucleotides (FMN) & flavin adenine dinucleotide (FAD)

• riboflavin in food can be its free form, bound to protein, or co-enzyme

  • only free riboflavin can be absorbed

riboflavin pathway

riboflavin sources

• green leafy crops

• bacterial synthesis (ruminants)

• eggs, milk, liver

• ↓ grains (corn, barley)

riboflavin functions

riboflavin (FMN, FAD)

• co-enzyme in oxidation-reduction rxns

• pyruvate dehydrogenase complex (& TCA cycle)

substrate channeling

• intermediate of multistep sequence never leave complex

• substrate channeling prevents theft of activated acetyl group by other enzymes

  • use this group as substrate

pyruvate dehydrogenase complex

pyruvate dehydrogenase cofactors

5 co-enzymes

• thiamine pyrophosphate (TPP)

• flavin adenine dinucleotide (FAD)

• co-enzyme A (CoA)

• nicotinamide adenine dinucleotide (NAD)

• lipoate

pyruvate dehydrogenase vitamins

4 vital vitamins

• thiamine (TTP)

• riboflavin (FAD)

• niacin (NAD)

• pantothenate (CoA)

FAD function

in TCA (krebs) cycle & energy generation

• FAD forms prosthetic groups of enzyme succinate dehydrogenase

• riboflavin reducing equivalent

  • FADH₂ is reduced → produce 2 ATP

FADH₂

cofactor to product 2 ATP

• reduced by riboflavin

riboflavin FA metabolism

role of riboflavin (FMN, FAD) in FA metabolism

• FAD is co-enzyme for Acyl-CoA dehydrogenase

  • break down of lipids → energy

• pyruvate dehydrogenatase glycolysis glucose breaks down (krebs cycle)

riboflavin complex locations

purine catabolism

DNA/RNA

• uric acid synthesis (birds & reptiles)

  • xanthine oxidase needs FAD

    • converts hypoxanthine → xanthine → uric acid

• amino acid transaminase (FMN, FAD) - nitrogen disposal

• glutathionine reductase - keeps FAD in reduced form of FADH₂

riboflavin requirements

• requirements ↓ w/ animal maturity (slow/no growth)

• ↑ requirement for repro states

• ruminants

  • mature - rumen microbial synthesis

    • slowly fermented substrates in rumen ↑ riboflavin synth. by bacteria

  • pre-ruminant - milk & supplements

• horses

  • microbe synth in cecum & colon provide some riboflavin

• monogastric

  • gut bcateria provides little unless coprophagy

  • based on E intake

riboflavin deficiency symptoms

niacin (B3)

• synthesized by animals & bacteria

• important coenzymes:

  • nicotinamide adenine dinucleotide (NAD)

  • nicotinamide adenine dinucleotide phosphate (NADP)

• FAD - enzyme

• FADH₂ - reduced form → generate 2 ATP

niacin (B3) sources

• sunflower meal

• peanuts

• meat, fish, liver

• yeast (distillers grain)

niacin synthesis

niacin synthesis species differences

• humans

  • 60 mg Trp → 1 mg niacin

• rats

  • 35-60 mg Trp → 1 mg niacin

• cats & ducks

  • almost no conversion

nicotinamide co-enzyme forms

NADH

• produced in catabolic rxns

• used in e^- transport chain to obtain energy by converting NADH → NAD+

• primarily produced in oxidative part of pentose phosphate pathway

glycolysis & krebs cycle

pentose phosphate pathway NADPH generation

FA synthesis

need niacin

• NADH₂ → e^- transport chain

• serve as E currency to build lipids

• synthesis of macronutrient uses up currency

niacin biochemical reactions

niacin pathway locations

niacin requirements

variation due to: Trip → niacin

niacin requirement factors

• genetics - faster growing animals

• ↑ production lvls

• ability to synthesize niacin from tryptophan

• exposures to feces (coprophagy, bacteria in feces)

• AA imbalances → reduce Trp use/absorption

  • e.g. branched chain AA antagonize

  • tryptophan absorption & uptake by tissues

• diet

  • e.g. corn protein

    • ↓ tryptophan & niacin is bound/unavailable

niacin deficiency

severe metabolic disorders of skin & digestive tract

• pellagra - Casal’s necklace

• black tongue - dogs w/ tongue & mouth inflammation

• 4 Ds

  • dermatitis

  • diarrhea

  • dementia

  • death

• glossitis

• gingivitis

• milkd

  • high blood lipids

  • LDL-cholesterol

tongue glossitis

• tongue is smooth, inflamed

• sore and hard to swallow.

pellagra (casal’s necklace)

pyridoxine (B6)

plant/bacteria synthesis only

• pyridoxol → pyridoxal → pyridoxamine

• coenzymes:

  • pyridoxal phosphate (amino group acceptor) → pyridoxamine phosphate (amino group donor)

B6 functions

essential role as coenzyme (pyridoxal phosphate PLP)

• over 50 enzymes rely on PLP, most associated w/ AA metabolism

  • transamination

    • exhcnage of amino (-NH₃) group of AA

  • decarboxylation

    • tyrosine → dopamine

    • -OH tryptophan to serotonin

  • deaminiation

    • remove amino (-NH₃) group

  • desulfuration

• needed for glycogen break down → glucose units

AA transamination

transaminase → B6

• thyroid - glucose metabolism

B6 desulfuration

• 1-carbon metabolism delivers 1-carbon moiety (methyl group) to many biologic reactions

  • nucleotide synthesis

  • biological methylation

    • needed to synthesize essential components of cells & tissues

    • maintain body homeostasis

• vit B6 is cofactor in carbon metabolism

  • take 1 sulfur → smth else

pyridoxyl phosphate niacin synthesis

pyridoxine complex locations

• AA metabolism

• carbon metabolism

• glucose metabolism

B6 requirements

↑ protein diet → ↑ B6 requirement

• ruminants

  • microbial synthesis adequate

• horses

  • synthesis in cecum but adequacy questionable

• rabbits & rats/mice

  • coprophagy provides enough

• humans

  • female contraceptives

  • antagonize conversion → PLP

• other species

  • dietary requirement

• all species

  • ↑ requirement w/ ↑ protein diets

B6 deficiency

• General symptoms – some related to Niacin synthesis

  • reduced growth

  • dermatitis

  • anemia – microcytic hypochromic

  • partial alopecia

  • epileptic-like fits/ hyperexcitable

• Symptoms due to role in AA Metabolism

  • ↓ nitrogen retention

  • ↓ feed protein utilization

  • excessive nitrogen excretion

  • impaired Tryptophan metabolism

• Vitamin B6 Deficiency & Cardiovascular Disease in Humans

• ↓ metabolism of Homocysteine to Cysteine → elevated lvls of Homocysteine in blood

pyruvate dehydrogenase complex (PDH or PDC)

• key regulatory site in cellular metabolism

  • by linking citric acid cycle & subsequent oxidative phosphorylation w/ glycolysis & gluconeogenesis

    • both lipid & AA metabolism

• carbohydrate stores reduced in mammals

• PDH activity is regulated downward to limit use of glucose by oxidative phosphorylation in tissues

  • can use FA or ketone bodies (heart & skeletal muscle)

  • important exception: neuronal tissue - processes glucose almost exclusively for ATP production

• activation of PDH both facilitates use of carbohydrate to meet energy demands

  • converts surplus dietary carbohydrates to FA for longer term energy storage

• perturbation of regulation of this choice of glucose or FA as energy source is key part of:

  • diabetes

  • metabolic syndrome and obesity

    • while metabolic substrate switching from oxidative phosphorylation to glycolysis defines the cancer phenotype, hence recent renewed interest in PDH activity and regulation

• PDH under tight & complex regulation

  • regulation by reversible phosphorylation in response to the availability of glucose