Vitamins (Week 4--Melega) Flashcards
What is a vitamin?
Molecules that humans cannot synthesize
Must be supplied in the diet
Usually are coenzymes for enzymatic reactions
Water soluble vs. fat soluble vitamins
Water soluble: taken into tissue until tissues saturated, then the rest is excreted (exception is B12, which we can store a lot of!)
Fat soluble: can accumulate with extra intake
What is a mineral?
Term mineral not used much anymore, because really these are ions (Na, Mg, P, S, Cl, K, Ca, Mg, Fe, Co, Ni, Cu, Zn…)
Required for nutririon also
Serve functional/structural roles and serve as electrolytes
Enzyme
Catalyst that lowers activation energy of a reaction
Coenzyme
Organic nonprotein small molecule that makes up part of the active site of the enzyme and needed for enzyme function (complete the structure of holoenzyme)
Vitamins or vitamin derivatives (NAD+, NADP+, FAD+ which all transfer electrons/H released by catabolic pathways)
Note: if it is NOT organic, then is called a cofactor (metal such as Fe, Mg, Zn)
B complex
Water soluble
Energy “fuel” metabolism (glycolysis then TCA)
B1 = thiamine
B2 = riboflavin
Niacin
B6 = pyridoxine
Pantothenate
Biotin
B12 = cobalamin
Vitamin C
Water soluble
Antioxidant, regenerates vitamin E
AKA ascorbic acid
Folate
Water soluble
DNA synthesis and 1 carbon transfers
AKA folic acid
Vitamin A
Fat soluble
Vision
Vitamin D
Fat soluble
Ca2+ absorption, bone growth
Vitamin E
Fat soluble
Antioxidant
Vitamin K
Fat soluble
Coagulation, vascular health
B1 (thiamine)
Converted to active form, thiamine pyrophosphate (TPP) in brain and liver
TPP is a coenzyme for:
1) Pyruvate dehydrogenase (PDH): pyruvate –> acetyl CoA for glycolysis and TCA
2) Alpha-ketoglutarate dehydrogenase (alpha-KGDH): alpha-ketoglutarate –> succinyl-CoA for TCA cycle
3) Transketolase: pentose phosphate pathway produces steroids, FAs, AAs, NTs, glutathione
Deficiency disease: peripheral nerve damage (Beriberi); CNS lesions (Wernicke-Korsakoff syndrome); thiamine deficiency common in alcoholics
B2 (riboflavin)
Precursor for flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD)
Flavoproteins (enzymes that need FMN or FAD) do redox reactions
Deficiency disease: lesions of corner of mouth, lips, tongue, seborrheic dermatitis
Note: FAD+ is an oxidizing agent (accepts electrons and becomes reduced) and FADH2 is a reducing agent (donates electrons and becomes oxidized)
B3 (niacin, or nicotinamide)
Required for synthesis of NAD+ and NADP+, cofactors for many dehydrogenases (lactate dehydrogenase, malate dehydrogenase) for redox reactions
Role in intracellular Ca2+ regulation and cell signaling
Deficiency disease: called pellagra–dermatitis, depressive psychosis, diarrhea (3 D’s for vitamin B3!)
Note: niacin isn’t a true vitamin bc can be synthesized endogenously from tryptophan but is VERY inefficient
Consequences of increased NADH/NAD+ ratio (in alcoholics)
Reduced hepatic gluconeogenesis
Decreased fatty acid oxidation
Increased fatty acid synthesis
Reduced activity of TCA (bc slowing rxns that depend on this ratio)
B5 (pantothenic acid)
Pantothenate required for synthesis of coenzyme A (CoA) and acyl carrier protein (ACP) domain of fatty acid synthetase
Everything (“pan-“) (70+ enzymes) need CoA to function!
Deficiency disease: peripheral nerve damage
B6 (pyridoxine, pyridoxal, pyridoxamine)
Converted to active form pyridoxal phosphate (PLP)
Coenzyme in enzymes for:
1) Transamination: required for synthesis and catabolism of AAs
2) Glycogenolysis: glycogen phosphorylase
3) Biosynthesis of NTs: GABA, 5-HT, DA, NE, EPI
4) Modylation of steroid hormone action
Deficiency disease: disorders of AA metabolism, convulsions
Note: some drugs (isoniazid and penicillamine) complex with pyridoxal and PLP to cause deficiency
Biotin (Vitamin H)
Required for enzymes involved in carboxylation (acetyl CoA carboxylase and pyruvate carboxylase)
Carboxylation reactions in gluconeogenesis, fatty acid synthesis, regulation of cell cycle
Deficiency disease: impaired fat and carbohydrate metabolism, dermatitis
Note: consumption of raw eggs can cause biotin deficiency because egg white protein (avidin) binds biotin and prevents intestinal absorption
B12 (cobalamin)
Transfer of one-carbon fragments and metabolism of folic acid (does homocysteine –> methioine)
Synthesized only by microorganisms; found in liver and tissues of animals, always bound to protein
Deficiency disease: pernicious anemia (megaloblastic anemia due to inability to do DNA synthesis (block purine and thymidine biosynthesis)), subacute degeneration of spinal cord, polyneuropathy (inhibition of fatty acid synthesis and destruction of myelin sheath)
Note: need intrinsic factor in order to absorb B12 in the ileum
How is vitamin B12 (cobalamin) absorbed?
Must be hydrolyzed from protein by gastric acid in stomach –> in ileum, B12 bound by intrinsic factor and absorbed into enterocyte –> vitamin transported to liver in blood bound to transcobalamin II –> delivered to target cells
Note: B12 can be stored in liver for ~6 years
Why isn’t B12 degraded by acid in the stomach?
Binds to haptocorrin (R-protein) secreted by saliva
What is the significance of B12 catalyzing homocysteine –> methionine reaction?
This reaction is needed for the “methionine synthase” reaction, to create the active form of folic acid (methyltetrahydrofolate –> THF (H4 folate))
Vitamin B12 deficiency causes accumulation of homocysteine and in other reaction, traps folate as methyltetrahydrofolate
Methionine synthase reaction is only known metabolic step where both vitamin B12 and folate are essential
What are the two reactions we need vitamin B12 for?
1) Homocysteine –> methoinine (thus methyltetrahydrofolate –> THF), needed for folic acid activation and now can’t do as much DNA synthesis (purine/thymidine biosynthesis blocked)
2) Methylmalonyl CoA –> Succinyl-CoA, causes demyelination/neurological problems because methylmalonyl CoA outcompetes malonyl CoA so malonyl CoA can’t synthesize fatty acids as well
Folic acid
Transfer of one-carbon units
Must be converted to tetrahydrofolic acid (THF (H4 folate), but there are many different THF derivatives that work) to be active (mostly reduced in liver)
Need folic acid to do DNA synthesis
Deficiency disease: megaloblastic anemia
How exactly does folate deficiency cause disruption of DNA synthesis?
Ultimately need N5, N10-Methylenetetrahydrofolate
To get this, dietary folic acid needs to get into cycle to create this
N5, N10-Methylenetetrahydrofolate needed to make purines directly and to make dTMP (nucleoside thymidine) via thymidylate synthase enzyme (which leads to DNA synthesis) when it continues in the cycle
Two ways dietary folates enter THF coenzyme pool/cycle?
1) Vitamin B12 reaction to THF
2) Folate reductase turns folic acid –> dihydrofolate which enters cycle to become THF
Other than DNA synthesis, what else are folates required for?
Biosynthesis of methionine and glycine
(Look at THF cycle)
What does your body do when it thinks you have a vitamin B12 deficiency?
N5, N10-Methylenetetrahydrofolate (what you want in the end) turns into N5-Methyltetrahydrofolate because that’s the substrate you need to make THF, but the problem is that the missing B12 is what’s needed to make that into THF so this is the “folate trap”
How does folic acid and/or vitamin B12 deficiency lead to anemia?
Inability to synthesize DNA during erythrocyte maturation leads to abnormally large erythrocytes (macrocytic/megaloblastic anemia)
Doesn’t cause problems in other cells’ DNA synthesis, weirdly enough…
Why do you need folic acid when you’re pregnant?
Increased number of rapidly proliferating cells in the blood
Need at least 600ug/day if intending to become pregnant
Need for folate nearly doubles by third trimester
Vitamin C
Hydroxylation of proline and lysine in collagen synthesis; antioxidant; enhances absorption of Fe (Fe3+ –> Fe2+); synthesis of DA, NE, EPI
Active form is ascorbic acid
After it reduces something, dehydroascorbate can be reduced back to active form by enzymes and glutathione
Deficiency disease: scurvy (impaired wound healing, subcut hemorrhage, soft swollen gums, osteoporosis, anemia)
Is it good to have lots and lots of vitamins?
If on healthy diet, no need to take extra vitamins
Most coenzymes (vitamins) cause adverse effects if you have too much
Note: vitamin C has hyperbolic curve, transporter function is saturated (active transport and simple diffusion) and after renal resorption threshold, vitamin C escess excreted in urine
Why does impaired DNA synthesis cause anemia?
For some reason it really affects RBC maturation and your RBCs get very large (megaloblastic anemia)
