Las Vitaminas Flashcards
Vitamins ?
organic compounds essential in small quantities to normal metabolism and must be supplied through diet
water-soluble vitamins ?
B1: Thiamine
B2: Riboflavin
B6: Pyridoxine
B12: Cobalamin
Niacin
Pantothenic acid
Folic acid
Biotin
Lipoic acid
Vitamin C: ascorbic acid
Fat-soluble vitamins
DEAK vitamin A: Retinol
Vitamin D: Cholecalciferol
vitamin E: alpha-tocopherol
vitamin K: phylloquinone
what are “activated carriers” ?
The activated carriers store energy in an easily exchangeable form, either as a readily transferable chemical group or as high-energy electrons, and they can serve a dual role as a source of both energy and chemical groups in biosynthetic reactions. For historical reasons, these molecules are also sometimes referred to as coenzymes. The most important of the activated carrier molecules are ATP and two molecules that are closely related to each other, NADH and NADPH
what is the reaction that takes place in the pyruvate dehydrogenase complex?
Pyruvate + coA + NAD+ –> acetyl coA + CO2 + NADH+ H+
the coenzymes involved in the pyruvate dehydrogenase complex ?
a total of 5 co-enzymes are involved in the PDC
thiamine/TPP> aldehyde group carrier that decarboxylates alpha keto acids
lipoic acid/lipoamide > acyl group carrier
pantothenic acid/coA> acyl group carrier
Riboflavin/FAD> oxidizing agent
Niacin/NAD+> oxidizing agent
function of TPP ?
TPP is a coenzyme derived from vitamin B1 (thiamine)
it functions as a carrier of an aldehyde group formed in the decarboxylation of alpha keto acids.
the TPP carbanion attacks the carbonyl carbon of pyruvate, CO2 is released –> hydroxy-ethyl TPP forms
other enzymes TPP is involved in ?
pyruvate dehydrogenase complex
alpha-ketoglutarate dehydrogenase complex
transketolase (pentose phosphate pathway and calvin cycle)
why might thiamine defieciency cause disease. Mention two thiamine (B1) deficiency diseases and elaborate on them.
Beriberi
Thiamine pyrophosphate, the biologically active form of thiamine, acts as a coenzyme in carbohydrate metabolism through the decarboxylation of alpha ketoacids. It also takes part in the formation of glucose by acting as a coenzyme for the transketolase in the pentose monophosphate pathway. transketolase connects the pentose phosphate pathway to glycolysis, feeding excess sugar phosphates into the main carbohydrate metabolic pathways. Its presence is necessary for the production of NADPH, especially in tissues actively engaged in biosyntheses,thiamine deficiency would disrupt carbohydrate metabolism and the production of NADPH stores and pentose sugars necessary for nucleotide synthesis.
symptoms:loss of appetite, constipation, nausea, depression, peripheral neuropathy, irritability, fatigue
confusion; ataxia (loss of control of bodily movements); confabulation; hallucinations; nystagmus(involuntary eye movements)
if genetic predisposition entails that your transketolase isoform(involved in the pentose phosphate pathway) has a low affinity for TPP, you are susceptible to WK syndrome
lipoic acid function ?
lipoic acid is covalently bound to a lysine residue on the host enzyme via an amide bond. in pyruvate dehydrogenase complex, ionized hydroxy-ethyl TPP attacks lipoamide –> acetyllipoamide (the new acetyl carrier) while hydroxy-ethyl TPP reverts back to TPP carbanion.
enzymes in which lipoamide is used ?
pyruvate dehydrogenase complex
alpha-ketoglutarate dehydrogenase
how is lipoic acid a major site for arsenic poisoning ?
arsenic binds reduced lipoic acid (dihydrolipoic acid) and oxidizes it, creating an inactivated protein complex incapable of receiving the acetyl group from hydroxy-ethyl TPP.
pantothenic acid and coenzyme A ?
give an enzyme example in which it’s used
Pantothenic acid is a component of coenzyme A. This coenzyme functions in the transfer of acyl groups such as in succinyl CoA and fatty acyl CoA.
what basically happens is that coA comes and forms a thioester linkage with an acyl group, splitting one compound into two.
CoA functions in the pyruvate dehydrogenase thiolase: it forms a thioester linkage with the acetyl group on the acetyl-lipoamide, freeing the dihydrolipoamide and forming acetyl coA.
how coA functions in fatty acid degradation ?
shortens the fatty acyl coA by a two carbon unit via forming a thioester linkage
lipoamide deficiency ?
Deficiency is very rare and symptoms are similar to other vitamin B deficiencies.
describe what happens in going from pyruvate into acetyl coA involving TPP, lipoamide, pantothenate (coA)
the vitamin niacin gives rise to what coenzymes ?
examples of enzymes in which NADH/NADPH are utilized ?
alpha ketoglutarate dehydrogenase (TCA cycle) NAD+
puruvate dehydrogenase NAD+
fatty acid synthase complex NADPH (reducing agent) for the two reduction steps
glucose-6-phosphate in the pentose phosphate pathway NADP+ used as oxidizing agent
dietary deficiency of niacin ?
ietary deficiency of niacin associated with the “3 D’s”: dermatitis, diarrhea, and dementia > Pellagra
skin; digstive system; nervous system
NAD is the sole substrate for PARP enzymes involved in DNA repair activity in response to DNA strand breaks; thus, NAD is critical for genome stability.
compare the relative ratios of NAD+/NADPH in the cell
Inside the cell the ratio of NAD+ to NADH is kept high, whereas the ratio of NADP+ to NADPH is kept low. This provides plenty of NAD+ to act as an oxidizing agent and plenty of NADPH to act as a reducing agent as required for their special roles in catabolism and anabolism, respectively.
Riboflavin/ Vitamin B2 derivatives ?
FMN and FAD are tightly bound coenzymes (prosthetic groups) in flavoproteins that catalyze many oxidation-reduction reactions involved in metabolism of fats, proteins, and carbohydrates.
examples of enzymes in which flavoproteins are used ?
succinate dehydrogenase [FAD]:
functions in both ETC and TCA cycle where succinate is oxidized into fumarate , reducing FAD into FADH
NADH-Q oxidoreductase (Complex I) [FMN]:
NADH is oxidized into NAD+ , transferring the electrons to FMN which in turn reduces Q into QH2
Acyl-CoA dehydrogenase [FAD]:
Beta oxidation !
B2 deficiency ?
Deficiency typically associated with deficiency of other vitamins in addition (malnutrition): cracked red lips, angular cheilitis, dry skin, iron-deficiency anemia, photophobia > ariboflavinosis
how does the cell discriminate between the NADH/FADH2 reserves within it ?
NAD+ receives a proton and 2 electrons to be fully reduced. while FADH2 receives two protons and two electrons to get fully reduced
go over pyruvate dehydrogenase complex again ?
Biotin ?
Biotin is a coenzyme in carboxylation reactions where it acts as a carrier of activated carbon dioxide (ATP-dependent step). Biotin is covalently bound to lysine in the biotin-dependent enzyme (prosthetic group). Carboxylation reactions occur in the metabolism of fatty acids as well as in gluconeogenesis.
enzymes in which biotin is used ?
phosphoenolpyruvate carboxylase: converts PEP into oxaloacetate
acetyl-CoA carboxylase: to make malonyl coA which later adds to acetyl coA in a condensation rxn in fatty acid synthesis
propionyl-CoA carboxylase: to create methyl malonyl coA and later succinyl coA (metabolism of odd chain fatty acids)
phosphoenolpyruvate carboxylase: converts PEP into oxaloacetate
anaplerotic role: To increase flux through TCA cycle, some of the PEP is converted to oxaloacetate by PEP carboxylase. Since the citric acid cycle intermediates provide a hub for metabolism, increasing flux is important for the biosynthesis of many molecules, such as for example amino acids.
acetyl-CoA carboxylase
rate-limiting step of fatty acid synthesis
to make malonyl coA which later adds to acetyl coA in a condensation rxn in fatty acid synthesis
propionyl-CoA carboxylase
to create methyl malonyl coA and later succinyl coA (metabolism of odd chain fatty acids)
pyruvate carboxylase
converts pyruvate into oxaloacetate
Pyridoxine ?
Vitamin B6 : Pyridoxal Phosphate (PLP) is the prosthetic group on all aminotransferases. Binds the donated amino group (Schiff base) and donates this amino group to the acceptor α-keto acid, producing an amino acid. Also deamination, decarboxylation, and condensation reactions involved in amino acid metabolism. Participates as a coenzyme in glycogen phosphorylation.
three enzymes in which pyridoxine/B6 is involved ?
Aminotransferases
glycogen phosphorylase- rate limiting step in glycogenolysis
serine dehydratase- goes from serine to pyruvate
B6 deficiency ?
Deficiency typically associated with pediatric malnutrition and symptoms include seizures, irritability, angular cheilitis –>B6 deficiency
connect amino acids to alpha keto acids with respect to body needs
cell running low on one redeems from the other
the two enzymes in the body that use B12 ?
Vitamin B12 is required for only two essential enzymatic reactions: methionine synthesis and isomerization of methylmalonyl CoA derived from the metabolism of odd-numbered fatty acids.
methionine synthase (aka homocysteine methyltransferase)
methylmalonyl-CoA mutase> in the metabolism of odd chain fatty acids : converts methyl malonyl into succinyl coA
link B12 deficiency to folic acid deficiency and megaloblastic anemia.
B12 deficiency —> loss of B12 DEPENDENT folate recycling —> folate deficiency —> megaloblastic anemia
BUT: if folate supplementation is present, DNA and RBC sythesis would no longer be folate dependent —> MASKING effect—> B12 pathologies compromised
contrast megaloblastic anemia with pernicious anemia.
Megaloblastic anemia (or megaloblastic anaemia) is an anemia (of macrocytic classification) that results from inhibition of DNA synthesis during red blood cell production due to folate deficiency. When DNA synthesis is impaired, the cell cycle cannot progress from the G2 growth stage to the mitosis (M) stage. This leads to continuing cell growth without division, which presents as macrocytosis.RBC’s stay in the enlarged, macrocytic form.
B12 is Absorbed in the GI tract after binding to intrinsic factor. In the absence of this glycoprotein, dietary B12 is not absorbed and the resulting anemia is called pernicious anemia.
folic acid and cobalamin- the big picture of 1-carbon metabolism ?
folic acid and nucleotide synthesis:
enzyme involved ?
intermediates ?
methotrexate ?
folate and cancer diagnosis ?
mention the group carried and the vitamin precursor
vitamin C deficiency ?
Deficiency leads to an unstable collagen triple helix so tissues with high collagen turnover are preferentially affected:
bleeding gums, easy bruising, slow wound healing, anemia, osteoporosis –> scurvy
biologically active form of Beta carotene ?
Rhetinol (vitamin A) is interconverted into Retinal; which is the photosensitive pigment in rhodopsin (in photoreceptor cells of the retina). Retinal could be irreversibly oxidized into rhetinoic acid, which is an important Ligand for nuclear hormone receptors that regulate gene expression (suppress keratin production for example). Controls patterning in embryogenesis.
vitamin D endogenous synthesis route ?
7-dehydrocholesterol is converted into cholecalciferol via UV light in the skin; cholecalciferol is then converted into D3 in the liver; D3 is then converted into the active form of the vitamin CALCITRIOL in the kidney where it binds a receptor in the cytoplasm–> the ligand-receptor complex translocates to the nucleus where it acts as a transcription factor promoting the expression of a gene encoding a calcium binding protein. Calcitriol increases the level of calcium (Ca2+) in the blood by increasing the uptake of calcium from the gut into the blood, and possibly increasing the release of calcium into the blood from bone (resorption).
calcitriol
warfarin business ?
The anticoagulant Warfarin (Coumadin) blocks the action of VKOR thereby decreasing the amount of mature clotting factors and subsequent risk for thrombosis.
summary
