Biochem Iii - Micronutrients

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Thiamine (activation)

Back 1

Phosphorylation

Thiamine PP kinase

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Thiamine (action)

Back 2

Pyruvate dehydrogenase complex

Alpha-KG dehydrogenase complex

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Pantothenic acid (action)

Back 3

Part of 1) coenzyme A, 2) acyl carrier proteins

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Thiamine (deficiency)

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Beriberi

Wernicke-Korsakoff Disease

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Pantothenic acid (deficiency)

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Dermatitis, alopecia, enteritis, adrenal insufficiency

*Affects systems with constant cell turnover

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Riboflavin (activation)

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Phosphorylation (to FMN)

Addition of adenine nucleotide (to FAD)

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Riboflavin (action)

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FMN: Co-factor for metabolic reactions, ETC

FAD: Co-factor in TCA cycle, amino acid, fatty acid degradation, NO synthesis

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Riboflavin (deficiency)

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Cheliosis and glossitis

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Niacin (activation)

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Converted, with nicotinamide and Trp (de novo) to form NAD+

NAD+ --> NADH by addition of hydride ion

NAD+ --> NADP+ by phosphorylation

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Niacin (action)

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NAD: Dehydrogenases, degradation reactions

NADP: Biosynthesis

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Niacin (deficiency)

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Pellagra: Dermatitis, diarrhea, dementia, death

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Biotin (activation)

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Freed (as biocytin) from Lys by biotinidase

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Biotin (action)

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Co-factor for Carboxylases (acts as carrier for CO2)

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Biotin (deficiency)

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Infants: Impaired growth, neurological problems

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Pyridoxine (activation)

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Phosphorylation to pyridoxine phosphate

Conversion to pyridoxal phosphate (PLP) by pyridoxine phosphate oxidase

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Pyridoxine (action)

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Co-factor for 5 enzyme families

1) Decarboxylases
2) Aminotransferases
3) Ser/Thr dehydratases
4) Aldolases
5) Hydroxymethyltransferases

Also req'd for glycogen phosphorylase

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Folate (activation)

Back 17

Released from glutamate by folate hydrolase

Converted via:

Folate --> DHF --> THF, uses NADPH in both steps

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Folate (action)

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Folate pathway, SAM pathway

Folate --> THF --> donates methyl to vitamin B12, which holds it in proper orientation for methionine synthase

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Folate (deficiency)

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Intestinal atrophy, macrocytic anemia, neural tube defects, elevated homocysteine

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Cobalamin/Vitamin B12 (activation)

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Requires intrinsic factor for uptake , bound in blood bound to transcobalamin

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Cobalamin/Vitamin B12 (action)

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Required co factor for 2 reactions

1) Methionine synthase
2) Methylmalonyl COA mutase

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Cobalamin/Vitamin B12 (deficiency)

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Same as with folate, causes elevated homocysteine

Pernicious anemia, due to deficiency of IF

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Vitamin K (action)

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Required for gamma-glutamylcarboxylase, converts Glu residues to Gla

Ca2+ binds to Gla residues, allowing coagulation proteins to associate with membrane, increases activity 10000x

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Vitamin C (action)

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Required co-factor for lysyl hydroxylase, prolyl hydroxylase

Convert lysine, proline --> hydroxyllysine, hydroxyproline

Used to cross-link collagen

Also neutralizes free radicals, converted back by dehydroascorbic acid dehydrogenase, ascorbate free radical reductase

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Vitamin C (deficiency)

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Scurvy: Bleeding gums, easy bruising, corkscrew hairs, petechial hemorrhages

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Vitamin E (action)

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Antioxidant, prevents non-enzymatic oxidation of polyunsaturated fatty acids

Reacts with free radicals to oxidized form, reduced by vitamin C

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Vitamin K (deficiency)

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Common in newborns, causes bleeding, given vitamin K at birth

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Beta carotene (action)

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Better antioxidant than other forms of vitamin A

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Beta carotene (excess)

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Causes yellow-orange discoloration of skin

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Retinal (activation/absorption)

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Beta carotene --> Retinal --> Retinol

Retinyl esters --> Retinol

Retinol --> Esterified retinol --> Chylomicrons --> Liver (storage)

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Retinal (action)

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Retinyl esters --> All-trans-retinol (retinol binding protein/transthyretinin) --> (retinal epithelial cells) --> 11-cis-retinol --> 11-cis retinal

11-cis retinal + opsin --> rhodopsin

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Retinal (visual cycle)

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Light --> 11-cis retinal --> All-trans retinal

Rhodopsin --> Metarhodopsin

Transducin (GDP-->GTP) --> Phosphodiesterase --> cGMP-->GMP --> Action potential

Metarhodopsin --> All-trans-retinol + opsin

All-trans retinol --> 11-cis retinol --> 11-cis retinal

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Retinoic acid (activation)

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Retinol --> retinal --> retinoic acid --> Bound to CRBP, RALBP, CRABP

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Retinoic acid (action)

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All-trans retinoic acid --> 9-cis retinoic acid

All-trans retinoic acid --> Retinoic acid receptor

9-cis retinoic acid receptor --> Retinoic acid X receptor

Retinoic acid X receptor --> Dimer/heterodimer --> Retinoic acid X response elements --> Developmental genes

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Vitamin A (deficiency)

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Night blindness

Bitot's spots, xerophthalmia, keratomalacia, follicular hyperkeratosis

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Vitamin D (action/synthesis)

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Diet --> Vitamin D2 (plants), vitamin D3 (animals)

7-hydroxycholesterol --> pre-vitamin D3 --> Vitamin D3 --> 25-hydroxyvitamin D3 (liver) --> 1,25-dihydroxyvitamin D3 (kidney)

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Vitamin D (action)

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1,25-dihydroxyvitamin D3 --> Vitamin D receptor

Vitamin D/Retinoic acid X receptor heterodimer --> Vitamin D response elements --> Downstream effects

Vitamin D --> Regulates synthesis of Ca2+ binding proteins involved in absorption of Ca2+ in intestines, retention in kidney

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Ca2+ homeostasis

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Low Ca2+ --> High PTH --> Retention of Ca2+ in kidney, release of Ca2+ from bones, increased hydroxylation of vitamin D3

High Ca2+ --> Low PTH --> Increased excretion in kidney, decreased hydroxylation of vitamin D3

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Phosphate homeostasis

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Low phosphate --> Low PTH --> Retention in kidney

High phosphate --> High PTH --> increased excretion of phosphate, inhibition of vitamin D3 hydroxylation

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Vitamin D (deficiency)

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Common in northern latitudes due to low sun exposure

Children --> Rickets

Adults --> Osteoporosis, osteomalacia

Excess --> Diarrhea, dermatitis, headache, nausea, anorexia, calcification of soft tissues