Micronutrients 3

Micronutrients 3: Micronutrients that act as enzyme cofactors: non protein that is needed for the enzyme to function. Co-enzymes: moves around in solution, acts as a substrate. Prosthetic group: physically held tightly Niacin (B3) •There are two forms: Nicotinic acid (from plants; provitamin) and nicotinamide (from animals, complexed with NAD when animal is alive). •Tryptophan can be used to synthesize the active form of Niacin: NAD (unphosphorylated or physphorylated). • NAD(P) is a dinucleotide (2 sugars + 2 bases + 2 phosphates) •NAD gets converted to nicotinamide when you kill an animal. • Involved in redox reactions where it can either accept (oxidizing agent, becomes reduced) or donate (reducing agent, becomes oxidized) electrons • NAD+ (active) and NADPH (active) • NAD+ accepts electrons in catabolic pathways (catabolic) •NADPH donates electrons in reducing pathways (anabolic) •NAD+ also breaks down to ADP ribose and nicotinamide. ADP ribose • Deficiency disease is pellagra; (dermatitis, dementia, diarrhea, death) epidemics historically due to dependence on corn as dietary staple Riboflavin (B2) • Plant provitamin is riboflavin • Active forms in animals are FMN and FAD • FMN is a mononucleotide (sugar + base + phosphate) • FAD is a dinucleotide (2 sugars + 2 bases + 2 phosphates) • Involved in redox reactions where it accepts (oxidizing agent, becomes reduced) electrons • Unlike NAD(P) which acts as a cofactor that can diffuse in solution, riboflavin cofactors are tightly bound prosthetic groups • Building on reaction of glutathione reductase described above, reaction of glutathione reductase: (1) regenerate GSH from oxidized GSSG (2) use electrons (2H) donated from NADPH, which are transferred to FAD that is tightly bound to the glutathione reductase enzyme. The FAD 3 FADH2 and passes these two electrons to GSSG. •FAD is the prosthetic group for GSSG • There is no clear deficiency disease, but if dietary intake is inadequate general symptoms will be observed, with the most distinctive being related to the mouth (cracks, inflammation) Thiamin • Typos in slides: slide 8 says thiamin triphosphate is TPP, should be TTP • Thiamin = plant provitamin • Add two phosphates = thiamin pyrophosphate (TPP) *Active • TPP has a carbanion that attacks carbonyl groups, and the phosphate groups attach to an enzyme allowing TPP to function as a cofactor • Also another form of thiamin, thiamin triphosphate (TTP), which is involved in nervous system function • TPP acts as a cofactor for: (1) pyruvate dehdrogenase complex (PDC)  involved in Decarboxylation reactions (2) alpha-ketoglutarate dehydrogenase (TCA) (3) transketolase • Deficiency disease is beriberi, and effects depend on stage of life: (1) older adults, mainly cognitive, “dry” (no swelling), (2) younger adults, cardiac, “wet” (swelling) (3) infant, extremely life threatening, cardiac Pantothenic Acid (PA) • PA is plant provitamin • 4-phosphopantethiene is active form in fatty acid synthesis • CoA (CoASH) is active form in catabolic reactions • No deficiency disease as widely distributed Biotin • No plant provitamin, just functions as biotin • Biotin acts as a cofactor for: (1) pyruvate carboxylase (2) acetyl CoA carboxylase (3) propionyl CoA carboxylase; allows carboxy