nutri sci - 1

WATER SOLUBLE VITAMINS 1

• vitamin C

  • can’t be synthesized by primates 

  • ascorbic acid or ascorbate

  • functions - antioxidant, cofactor in synthesis of collagen 

    • cofactor in reactions to synthesize things like carnitine, serotonin, norepinephrine

  • absorption - active transport via SCVT1 and 2

    • brush border enzymes

    • water soluble directly into blood 

    • excess filtered out by kidneys and removed in urine 

  • toxicity - nausea, cramps, diarrhea

  • deficiency

    • death from internal bleeding (months of deficiency)

  • RDA - 75-90 mg per day

    • 100 mg per day = tissue saturation

  • sources - citrus fruits, tomatoes, potatoes, veggies

• B Vitamins

  • energy metabolism

  • absorbed in small intestine

  • sometimes passive but most often facilitated or active transport 

  • Thiamin (B-1)

    • function - thiamin pyrophosphate 

      • TPP is a coenzyme in multiple metabolic pathways - decarboxylation

        • pyruvate dehydrogenase 

        • decarboxylation of alpha-keto acids

        • transketolase activity

          • basis for testing thiamin adequacy

        • neurotransmitter synthesis 

    • absorption, transport, storage, excretion

      • active transport via specific transporters 

      • also simple diffusion

      • travels through blood generally bound to albumin

      • not much storage - primarily liver

      • excreted in urine

    • deficiency 

      • consequence of insufficient food intake to meet energy needs 

      • malnourished and homeless more susceptible

      • beriberi disease from prolonged deficiency

        • wet - affects cardiovascular system; fast heart rate, shortness of breath, leg swelling

        • dry - affects nervous system - numbness in extremities, confusion, pain

        • both have symptoms of peripheral neuropathy

    • requirements

      • transketolase activity in red blood cells 

      • RDA: 1.2 mg/day

      • NO UL

    • sources

      • pork products, some wheat products 

WATER SOLUBLE VITAMINS 2

• Riboflavin (B2) - fluorescent yellow compound 

  • functions - component of two coenzymes 

    • flavin mononucleotide, flavin adenine dinucleotide

    • sometimes used in food as a coloring agent

  • FMN

    • integral part of ETC

  • FADH2/FAD

    • involved in beta-oxidation of fatty acids 

    • conversion of tryptophan to niacin

    • reduction of oxidized glutathione reductase

  • absorption, storage, transport

    • absorption in small intestine - active transport and passive diffusion

    • circulation in the blood

    • minimal storage => usually converted to FMN/FAD

    • excretion via kidneys and urine 

  • most people exceed the RDA daily

  • recommendations

    • levels are assessed based on glutathione reductase activity in RBCs

    • no UL has been established 

• deficiency

  • ariboflavinosis

    • very uncommon usually associated with other B vitamin deficiencies 

    • symptoms - glossitis, stomatitis, cheilosis

    • more common in elderly or alcoholics 

  • nutrient drug interaction

    • phenobarbital - sedative 

      • metabolism of this drug causes dramatically increased utilization of riboflavin

      • often provided a riboflavin supplement for those individuals that are prescribed phenobarbital

• food sources

  • dairy products

    • free vitamin first found in milk and where it was isolated from

  • sensitive to UV light 

• Niacin (B3)

  • function

    • cofactor - NAD and NADP

    • involved in many central energy metabolism reactions (NADP) participates in biosynthesis 

    • turning of the TCA cycle produced reduced NADH

      • NADH delivers these electrons to the ETC - movement of electrons down the chain drives proton pumping and enables synthesis of ATP

  • absorption, transport, secretion

    • facilitated transport or passive diffusion

    • can be synthesized from tryptophan, although this is a minor contributor 

    • travels through blood 

    • not much storage - liver can convert some excess plasma nicotinamide to NAD storage 

    • excreted in urine 

  • RDA

    • intake typically exceeds recommendations

    • can be made from tryptophan

• deficiency

  • pellagra

  • 4Ds - dementia, diarrhea, dermatitis, death

• toxicity

  • megadoses - 1.5 - 2g/day may decrease LDL and increase HDL

  • niacin flush - diluted capillaries and potentially painful tingling sensation 

  • liver damage for prolonged high doses 

• food sources

  • meats, poultry, seafood, some nuts (peanut butter)

WATER SOLUBLE 3

• pantothenic acid (B5)

  • functions - precursor and component of the synthesis of Acetyl-CoA

    • also used by acyl-carrier protein that requires 4’-phosphopantetheine as a prosthetic group

    • involved in reactions for lipids, neurotransmitters, steroids, hemoglobin

  • absorption, storage, transport

    • absorption in small intestine

    • most of this in diet is in the CoA form

    • circulation in blood

    • minimal storage

    • excretion of excess via kidneys/urine

  • AI/UL

    • 5 mg/day

    • widely available in foods

      • beef liver great source

    • no established toxicity (diarrhea possible)

  • deficiency

    • very rare 

    • general failure of all of body’s systems

      • fatigue, GI stress

    • nutrient drug interaction: estrogen-containing oral contraceptives may increase requirements 

• Biotin (B7)

  • functions

    • wide range of metabolic processes 

      • especially utilization of fats, carbs, or amino acids 

      • notable - Acetyl-CoA carboxylase

        • irreversible, committed step of fatty acid synthesis

  • absorption, transport, storage, excretion

    • facilitated transport

    • must be released from food 

      • most is protein bound so it gets released from peptides by the brush border enzyme biotinidase 

    • travels through the blood

    • some storage in liver 

    • excreted in urine 

    • some evidence that the large intestine microbiota can synthesize comparable amounts to what is available from the diet 

  • RDA/UL

    • 30 ug/day

    • UL not established 

    • widely available in food 

      • eggs, liver, yeast

      • also produced by gut bacteria

  • deficiency

    • very rare

    • can be induced from diet of raw eggs 

      • several dozen per day for months

    • symptoms - skin rash, hair loss, neurological impairment 

    • genetic - biotinidase deficiency is autosomal recessive 

      • impairs intestinal absorption of biotin

      • screened for in newborns 

• pyridoxal (B6)

  • functions - Cofactor: phosphate involved in ~4% of all enzymatic reactions

    • hemoglobin and amino acids biosynthesis

    • fatty acid metabolism

    • glycogen phosphorylase 

    • gluconeogenesis

    • neurotransmitter biosynthesis

  • absorption, storage, transport

    • absorption in small intestine mostly passive diffusion

    • must be de-phosphorylated to be absorbed 

    • liver processes the vitamin to PLP

    • sent out via blood from liver bound to albumin

    • some storage - liver but also muscle

    • excretion via kidneys and urine in form of 4-pyridoxic acid 

  • RDA/UL

    • 1.3 mg/day

    • UL - 100 mg/day

      • peripheral neuropathy

    • toxicity - 500 mg/day for months

  • deficiency

    • pretty uncommon, alcoholics at greater risk 

    • microcytic hypochromic anemia

      • small, pale red blood cells due to impaired hemoglobin synthesis 

      • seborrheic dermatitis

      • depression, confusion, convulsions 

      • impaired immune function 

    • drug interactions

      • L-DOPA (parkinsons)

      • Isoniazid (TB)

  • sources - meat, fish, potatoes, some veggies. foods will lose some during cooking. less bioavailable in some plant sources 

WATER SOLUBLE VITAMINS 4

• Folate (B9)

  • functions

    • 5 coenzyme forms, derivatives of tetrahydrofolic acid 

    • move around single carbons 

    • essential for DNA synthesis and repair (crucial for cell divison) 

    • methotrexate

      • ability to inhibit DNA synthesis is a very useful trait for cancer treatment 

      • chemotherapeutic agent that is an antagonist of folate

      • treats rheumatoid arthritis 

      • folate supplements prescribed to minimize toxic effects

        • skin cells, white and red blood cells, intestinal lining

    • homocysteine metabolism

      • intermediate between methionine and cysteine

      • high levels of homocysteine in the blood correlated with CVD 

      • Vitamins B6, B9, and B12 lower homocysteine levels in blood 

  • absorption, transport, storage, excretion

    • absorbed in small intestine 

      • we only absorb the monoglutamate form - folate conjugases in small intestinal epithelial cells break down the polyglutamate

    • active and passive transport 

    • circulation in blood 

    • liver processes the monoglutamate form to polyglutamate 

      • we store a limited amount in liver 

    • we typically excrete a very small % of intake via urine 

    • enterohepatic circulation

      • liver incorporates excess folate into bile 

  • deficiency

    • circumstances

      • low intake/absorption (alcoholics)

      • increased requirement (pregnancy)

      • low utilization (B12 deficiency)

      • excess excretion (prolonged diarrhea)

    • megaloblastic anemia

      • RBC lifespan - 120 days

      • decreased DNA synthesis in progenitor cells in bone marrow

      • protein synthesis continues but cell divisions slow, cells become enlarged 

    • steps - takes about 2 weeks for onset of folate-free diet

1. decrease in blood [folate]

2. decrease in RBC folate

3. defective DNA synthesis

4. structure change in some white blood cells

5. increase in blood [homocysteine]

6. megaloblastic changes in bone marrow

7. RBC size increases

8. megaloblastic anemia

• neural tube defects

  • folate necessary for closing neural tube 

• anencephaly

  • no brain develops

  • depending on severity may see paralysis, incontinence, hydrocephalus (water), learning disabilities 

• recommendations

  • RDA = based on amount needed to maintain RBC folate levels

    • 400 ug/day

  • UL

    • 1 mg/day

    • can mask B12 deficiency

    • supplements are regulated 

• sources

  • green leafy veggies, dairy products not a good source

  • heat, light, and air sensitive 

• cobalamin (B12)

  • R moiety: methyl, hydroxyl, cyano

  • function 

    • coenzyme for methionine synthase 

      • interaction with folate 

    • necessary for normal nerve development (myelin formation)

  • absorption, transport, storage, excretion

    • R-protein (Haptocorrin)

      • glycoprotein produced by salivary glands 

      • functions to protect acid-labile cobalamin while it moves through the stomach 

    • stomach HCl/pepsin release proteins bound to B12

    • intrinsic factor released by stomach

    • R-protein is degraded in small intestine, intrinsic factor then binds to B12

    • absorption in the ileum

    • transcobalamin 2 is a protein inside epithelial cells that binds to B12

      • complex enters the blood

    • ~50% of dietary B12 absorbed

    • travels to liver, bone marrow, RBCs

    • excretion

      • enterohepatic circulation

      • some storage in liver

  • intake

    • RDA = 2.4 ug/day

    • only made by certain bacteria and archaea

    • UL not established 

  • deficiency

    • typically result of impaired absorption rather than low intake

      • defects in R-protein or intrinsic factor

      • treated heartburn/ulcers

      • GI surgery

      • tapeworms

      • bacterial overgrowth in small intestine

      • chronic malabsorption 

    • symptoms

      • pernicious anemia - identical to folate deficiency

      • neurologic symptoms

        • peripheral neuropathy

        • gait ataxia

        • memory loss/cognitive impairment 

        • myelin sheath damage

      • masking by folate supplementation

  • food sources

    • animal origin (meat, dairy products) or fortified foods 

    • vegetarians need a supplement

    • individuals over 50 years of age likely also benefit from supplementation

      • malabsorption is more likely in advanced age individuals