BIOCHEMISTRY- Vitamins Videos Flashcards
Which vitamins are related to Biotin?
Pyruvate carboxylase
Acetyl CoA carboxylase
Propionyl CoA carboxylase
Which pathway is related with Biotin and Pyruvate carboxylase?
Gluconeogenesis
Which is the most common cause of Biotin deficiency?
(RARE) Excessive consumption of raw eggs which leads to hypoglicemia
In which pathway do we see Acetyl CoA carboxylase and Biotin?
Fatty Acid synthesis
In which pathway do we see Propionyl CoA carboxylase and Biotin?
VOMIT pathway
Odd carbon fatty acids
Val, Met, Ile, Thr
Clinical findings of Biotin deficiency
Alopecia, bowel inflammation, muscle pain
Which vitamin is Thiamine?
B1
Which enzymes ate related to Thiamine?
Dehydrogenases:
Pyruvate dehydrogenase
α ketoglutarate dehydrogenase
What is the function of dehydrogenases?
Tightly associated to energy production
In which pathway do we see pyruvate dehydrogenase?
PDH
Pathway related to α ketoglutarate dehydrogenase
TCA cycle or Krebs Cycle
What is the product of pyruvate?
Acetyl CoA
What is one of the main importance of Thyamine?
ATP production due to its relationship with enzymes
How is the pathogenesis of thiamine deficiency?
CNS with no energy→ Na+ pump fails → Na+ stays intracellularly → the cell starts swelling → cell ruptures and it starts Neurologic failure
In which patients is thiamine deficiency more common?
Alcoholism (alcohol interferes with absorption)
Pathology associated with vitamin B1 deficiency
Wernicke Korsakoff Syndrome
Beri beri disease
Characteristics of Wernicke Syndrome
Ataxia, nystagmus, ophtalmoplegia
Characteristics of Korsakoff Syndrome
Confabulation, psychosis
One of the main structures damage in Thiamine deficiency
Destroys mammilary bodies (part of the limbic system)- patients confabulate
In case of Vitamin B1 deficiency, what is the treatment?
Supplementation of thiamine and Glucose
What is Dry beri beri?
Wernicke Korsakoff Syndrome
When is just Thiamine alimentary deficiency (not related to alcohol abuse)? What is the probable disease?
Wet beri beri
How else is wet beri beri adquired?
By eating rice that has been husked (white rise)
Very unusual
What is affected in wet beri beri?
Heart, High output, cardiac failure
Pathogenesis of wet beri beri
- Thiamine deficiency
- Kreb cycle ATP ↓ (no energy)
- Cells start swelling
- Organomegally
- Dilated Cardiomyopathy → systolic failure (dropping ejection fraction → Congestive heart failure
Which other enzymes are related to Thiamine?
Transketolase
Branched chain ketoacid dehydrogenase
In which pathway is Transketolase related?
HMP shunt
Which is the only cofactor needed by transketolase?
Thiamine (vitamin B1)
Which is the lab test for Thiamine deficiency?
Transketolase activity (Because transketolase only requires Thiamine as a cofactor to work)
Which is the importance of Branched chain ketoacid dehydrogenase?
Metabolism of Valine, isoleucine and leucine
Which Pathology is associated with Branched chain ketoacid dehydrogenase?
Mapple Syrup Urine disease
Which vitamin is Niacin?
B3
What is made with Niacin?
NAD (H)
NAPD (H)
Enzymes related to vitamin B3?
Dehydrogenases
In which patients is Niacin deficiency seen?
In malnourish and eldery “tea and toast”
Vitamin deficient in Pellagra
Vitamin B3 (Niacin)
Clinical findings of Pellagraa
3 Ds: Diarrhea, Dementia, Dermatitis, and if not treated Death
When you run our of Niacin what happens?
Source of electrons, for electron Transport chain to make ATP
What else is related to Pellagra?
Deficiency of tryptophan
Which is the major dietary staple of Tryptophan?
Corn
What is Hartnup disease?
Deficiency of Decrease uptake of tryptophan by kydney
What other disease is associated with Hartnup disease? Why?
Mild Pellagra, because Tryptophan is requireed for Niacin formation and because Try is decreased, Niacin is also decreased
In which food is folic Acid Obtained?
Leafy type of vegetables
Which enzyme requires folic acid ?
Thymidilate synthase
Enzyme in purine synthesis
Active form of Folic acid
THF
Which is the function of Thymidilate synthase?
Conversion of Uracyl to Thymidine
What is the final result of Folic acid deficiency? Why?
↓ DNA formation, because of ↓ Thymine
What is made with THF?
Adenine and Guanine
What is the final result of the THF deficiency?
↓ DNA synthesis due to decrease of Adenine and Guanine
In which patients is folic acid deficiency more common?
Alcoholics and pregnancy
and when we grow to quickly
How long does the body stores folic acid?
Body stores depleted in 3 months
Findings of folic acid deficiency
Megaloblastic anemia
Homocystinemia
What is found in the blood with Megaloblastic anemia?
Hypersegmented neutrophils and Macroovalocites
What risk is increased with homocystinemia?
Deep vein thrombosis and atherosclerosis
Which vitamin deficiency can cause homocystenimia?
Folic acid
B12, B6
Alternative name for Vitamin B12
Cyanocobalamin
How much is Vitamin B12 associated with poor diet?
Poorly associated
For how long can we store vitamin B12?
For decades
Which enzymes are related to vitamin B12?
Homocysteine methyltransferase
Methylmalonyl CoA mutase
What is the function Homocystine methyltransferase?
Untraps folate from the storage form, and folate is inactive when is the storage form (Ns Methyl THF)
What is the result of homocytine methyltransferase deficiency cause by Vitamin B12 deficiency?
Megaloblastic Anemia, because traps folate in its inactive form
What pathway is related to methylmalonyl CoA mutase?
VOMIT pathway
Odd carbon fatty acids,
Val, Met, Ile, Thr (They accumulate)
Importance of Methylmalonyl CoA mutase
Source of Succinyl CoA require for Kreb cycle, so no ATP when vitamin B12 is deficient
What is the finding of failure of Methyl CoA mutase due to Vitamin B12 deficiency?
Progressive peripheral neuropathy
Type of neuropathy seen with vitamin B12 deficiency
Subacute combined Degeneration of the spinal cord (posterior and lateral column)
Type of Motor neuron damage seen in Neuropathy of Vitamin B12 deficiency
Upper motor neuron syndrome
In which situations is subacute combined degeneartion of the spinal cord seen?
Vitamin B12 deficiency
HIV
Friedrich Ataxia
Which is the most common cause of Vitamin B12 deficiency?
Pernicious anemia
What is Pernicious anemia?
Autoimmune disease of the stomach, antibodies bound to parietal cells and intrinsic factor (require for vitamin B12 absorption)
Other causes of Vitamin B12 deficiency
Also in aging Poor nutrition Bacterial overgrowth of terminal ileum Resection of terminal ileum Secondary to Crohn disease Chronic Pancreatitis Rarely in vagus or infection with D. Latum
Alternative name for Vitamin B6
Pyridoxine
How is Vitamin B6 used?
As pyridoxal- P (PLP) by every single Aminotrasferases (transaminase): AST (GOT), ALT (GPT)
What is the function of Aminotransferases?
Detoxify ammonic
What is ammonia?
A strong base that can disolve lipids of membranes
How is ammonia detoxified?
By the liver
What happens when having liver injury, how is ammonia affected?
The liver start producing Amminotrasferases, making sure that ammonia isn’t free to damage further tissue and B6 is decreased as a result
How do liver enzynes affect vitamin B6?
↑ AST/ ALT chronically , leads to B6 deficiency
Most common cause of Vitamin B6 deficiency
Alcohol (hepatitis) —> Cirrhosis
Which is the drug that most common cause vitamin B6 deficiency?
Isoniazid therapy
What other use does Pyridoxine have?
Heme synthesis
Which enzyme use vitamin B6 as a cofactor for Heme synthesis?
δ Aminolevulinate synthase
Type of anemia in Pyridoxine deficiency
↓ Heme synthesis → ↓ Hv → Mycrocytic anemia → ↓Iron build up → Sideroblastic anemia
Other clinical findings of Vitamin B6 deficiency
Cheilosis or Stomatitis (cracking or scaling of lip borders and corners of the mouth)
Convulsions due to ammonia accummulation encephalopathy
Alternative name for Rivoflavin
Vitamin B2
What is made with vitamin B2?
FAD (H2)
What does FAD produces?
Electrons
Pathways where FAD is realted
Succinate DH (TCA cycle)
Fatty Acyl CoA dehydrogenase (P oxidation)
Glysol phosphate dehydrogenase shuttle
When do we commonly see Vitamin B malnutrition?
In parenteral nutrition
Clinical findings of Rivoflavin Deficiency
Corneal neovascularization
Cheilosis or Stomatitis
Magenta colored tongue (due to glositis)
When is Ascorbate deficiency seen?
Diet deficient in citrus fruits and green vegetables
Alternative name for Vitamin C
Ascorbate
Which enzymes depend on Vitamin C?
Prolyl and lysyl hydroxylases
Dopamine hydroxylase
What is the function of Prolyl and lysyl hydroxylases?
To make stable collagen
Clinical findings of Ascorbate deficiency related to deficient collagen synthesis
Easy bruising (perifollicular hemorrhage), bleeding gums, poor wound healing, increased bleeding time
Which other vitamin deficiency is differential diagnosis of Vitamin K?
Vitamin C, but vitamin C has increased bleeding time due to defective aggregation of platelets
What is the function of Dopamine hydroxylase?
Converts Dopamine to Norepinephrine
Which vitamin deficiency affects catecholamine synthesis?
Ascorbate (vitamin C) due to Dopamine hydroxylase failure
When Vitamin C deficiency affects Catecholamines synthesis, what is the result?
Autoimmune Nervous system specially sympathetic
and Central Nervous system causing depression
What does Vitamin C have to do with Iron?
Allows tha absorption of Iron in GI tract
In which form does Iron come from vegetables?
Fe3+
Can we absob Fe3+?
No
What is needed to absorb Fe3+?
Stomach H+ and vitamine C so it is converted to Fe2+
Disease caused by Vitamin C deficiency
Scurvy
Is panthothenic acid water soluble or fat soluble vitamin?
Water Soluble
What is made with panthothenic acid?
CoA–> AcetylCoA
Can you live without panthotenic Acid?
NO, because it makes Acetyl CoA, substrate needed for TCA cylce
Which pathways require Panthotenic Acid?
Fatty acid metabolism
PDH
TCA cycle
Which vitmain is needed for CoA synthesis?
Panthotenic Acid
Alternative name for Vitamin D
Cholecalciferol
Functions of Vitmain D
In response to hypocalcemia, helps normalize serum calcium levels
Phosphate homeostasis
From where does Vitamin K come?
Menaquine, bacterias
Phytoquinone, plants
Important functions of Vitamin K
Carboxylation of glutamic acid residues in many Ca2+ - binding proteins
Importantly coagulation factors II, VII, IX, X as well as protein C and S
Alternative name for Vitamin E
α Tocopherol
Functions of Vitamin E
Antioxidant in the lipid phase, protects membrane lipids from peroxidation
What is the effect of 1,25 hydroxycholecalciferol?
Bone: Osteoclasts- Ca2+ mineralization or mobilization (with PTH)
Intestine: (Duodenum) increase calcium uptake from intestine
Kidney: Ca2+ Reabsorption, BUT increases retention of PO4 3- (Phosphate)
What is the difference on effects of PTH compared to Calcitriol?
PTH increases phosphate excretion
Calcitriol increases phosphate phosphate reabsorption
In which food is vitamin D3 found?
In salt water fish (salmon) and egg yolks
Added to milk and some fortified cereals
Which pathologies may affect vitamin D?
Cirrhosis and liver failure may produce bone mineralization
End stage renal disease
Main causes of cirrhosis
60% chronic alcoholism
20% hepatitis viruses
15% cholestatic issues (gallstones) fibrosis of billiary duct
5% Weird metabolic diseases like Wilson, etc
What do patients with end stage renal disease develop?
Renal osteodystrophy, with vitamin D lack because 1 hydroxylation can’t be done, developing hypocalcemia and secondary hyperparathyroidism–> Loss of PO4 3-
In case the patinet has either liver failure or renal failure how does Vitamin D should be administered?
Depending on the pathology it should be administer in its proper hydroxylated form
In case of Renal failure, which is the the vitamin D from that should be administered?
In 1,25 hydrocholecalciferol form
In liver failure or cirrhosis which is the form that vitamin D should be administered?
In 25 hydrocholecalciferol
What is the effect of Vitamin D deficiency?
↓ Ca2+ → secondary ↑ PTH
Bone demineralization
Rickets (children)
Osteomalacia (adults)
Causes of vitamin D deficiency
Insufficient sunlight
Inadequate fortified foods (milk)
End stage renal disease (renal osteodystrophy)
Liver failure or cirrhosis
Which renal calcification is seen in renal osteodystrophy?
Metastatic calcification
Finidngs on the bone when renal osteodystrophy
Brown cyst called von Recklinhausen of the bone
When is Vitamin D dietary supplementation needed?
If inssuficient exposure to UV light
Before getting to Cholecalciferol what is first?
7 Dehydrocholesterol
What is needed from the conversion of 7 dehydrocholesterol to cholecalciferol?
UV light
Alternative name for Vitmain D3
Cholecalciferol
What is needd for cholecalciferol to be activated?
Hydroxylation
Where is cholecalciferol found?
In the liver
First enzyme needed for hydroxylating cholecalciferol?
25 hydroxylase
What is the result of cholecalciferol hydroxylation?
25- hydroxycholecalciferol
Where is 25- hydroxycholecalciferol found?
In kidney
What is needed to make 25 hydroxylase?
Have a good liver
Which enzyme is required for 25 hydrocholecalciferol in order to become active?
1 α hydroxylase
Which is the active form of cholecalciferol?
1, 25 hydroxycholecalciferol
Alternative name for 1, 25 hydroxycholecalciferol
Calcitriol, 1, 25 - DHCC
What is the result of ↓ Ca2+?
PTH production
Waht is the effect og PTH?
Bone resorption ↑ Ca2+
Kidney ↑ Ca2+ reabsorption to the expense of phosphate PO4 3- (pee)
What induces action of 1 α hydroxylase?
PTH
Why does PTH induce 1 α hydroxylase?
Because that is the way it controls indirectly Ca2+ regulation in the gut, because it doesn’t have receptor in there
What is the result of vitamin D toxicity?
In hypecalcemia, but primarily which can impair renal function
Early signs of Vitamin D toxicity
Polyuria, Polydipsia and nocturia
What is the effect on the bone if taking too much vitamin D?
Its going to break the bone
What is consider Vitamin D toxicity?
Taking 10-15 times of what FDA recommends
Main functions of Vitamin A
Maintenance of healthy epithelium
Vision
Which are the three structures of how Vitamin A may be presented?
Hydroxyl (retinol)
Carboxyl (retinoic acid)
Aldehyde (retinal)
Which vitamin forms are required for the growth, differentiation and maintenance of epithelial cells?
Retinol and retinoic acid
Which vitamin A form is important for vision/
Retinal
Where do we store vitamin A?
In the liver in Stellate cells (Ito cells)
What is the importance of Ito cells?
They behave as fibroblast in the liver, work in liver injury, the one thath result in cirrhosis
Store of vitamin A
Which vitamin A form is lacking in night blindess?
Retinal deficiency
In case of Retinol and retinoic acid deficiency, where can we find keratinuzed squamous epithelia?
In the lung
In the eyes, causing Xerophthalmia, Bitot Spots (opaque spots/ ulcers on sclera and cornea)
What is Keratomalacia?
Destruction of the cornea
Causes of Vitamin A deficiency
Fat malabsorption
Fat free diets
Findings of Vitamin A toxicity
Excessive sweating, brittle nails and diarrhea
What are Outter Rod cells?
Photoreceptors in the retina, neurons
What do eye Neurons produce when stimulated?
Glutamate (excitatory)
What do Rod cells excite?
Bipollar cells
What does Bipollar cell produces?
GABA containing nuerons in optic nerve (inhibitory)
What happens if ↑ GABA are produced?
Blindness, because it inhibits optic nerve
What is necesary to see?
↓ Glutamate produced by Rod cells → ↓GABA → disinhibition of optic nerve → you can see
In order to have night vision what is needed?
Shut down Rod cells
Type of protein found in Rod cells that forms the receptor
Rhodopsin (light receptor) → senses photones of light
What kind of receptor are Rod Cells?
Light receptor
When does the Rhodopsin receptor work?
During night time only because thay only work when few photones
What composes Rhodopsin?
Protein transmembrane and retinal
Which are the two forms in which Retinal exist?
Trans
Cis
Once Rhodopsin is exposed to photones what happens?
Trans is changed to cis and transmembrane protein activates Gt protein
Type of transmembrane protein of Rhodopsin
7 domain
Which enyme is activated by Gt protein after Rhodopsin is stimulated?
cGMP PDE (Phosphodiester)
What is the function of cGMP in Rod cells?
It keeps open Na+ channel and Na+ keeps the cell depolarized (↑ Glutamate) → can’t see in darkness
Who inactivates cGMP?
cGMP PDE
What is the function of cGMP PDE?
Inhibits cGMP → Closses Na+ channels → Cells hyperpolatized (↓ Glutamate) → Night vision is possible
Which gene translocation is seen in Vitamin A receptor on promyelocytes?
t (15; 17)
Which is the basis of treating AML M3?
Administration of high dose vitamin A because work in t(15; 17) receptor on promyelocytes, making it myelocyte → metamyelocyte → band→ Neutrophil (PMN)
At which point of differentiation does a prmyelocyte stop differentiating?
Myelocyte → Metamyelocyte
For what is Vitamin K required?
To introduce Ca2+ binding sites on several calcium dependent proteins
What are the modifications that vitamin K does to introduce Ca2+ binding site?
γ carboxylation of glutamyl residue(s) in these proteins, often identified the γ carboxylation of glutamic acid
Which proteins undergo vitamin K dependent carboxylation?
Coagulation factors II (prothrombin), VII, IX, and X and anticoagulant C and S
What do coagulation factors II, VII, IX, X and anticoagulant C and S require?
Require Ca2+ for ther function
Where does γ carboxylation is done?
In hepatocytes, NOT in the blood
Which enzyme is activated by vitamin K in order to make γ carboxylation?
By γ glutamyl carboxylase
What does Carboxylation means by vitamin K?
Adding another Carboxyl group –> Add negative charges –> Add of Ca2+ (only adequate γ carboxylation)
What is the effect of activated prothrombin?
Convertion of Fibrinogen to fibrin and make the thrombus
What is associated to vitamin K deficiency?
With significant bleeding
Which drugs look like vitamin K and block γ carboxylation of glutamate?
Warfarin
Dicumarol
Symptoms found in Vitamin K and C deficiency
Easy bruising, bleeding
Vitamin K or C deficiency …. Increased bleeding time
Vitamin C deficiency
How is bleeding time in vitamin K deficiency?
Normal
Vitamin K or C deficiency…. Increased PT
Vitamin K deficiency
How is PT in vitamin C deficiency?
Normal
What is the difference in clinical findings between vitamin K and Vitamin C deficiency?
In vitamin K deficiency we only see Hemorrhargic disease with no conective tissue problems
What is associated with vitamin K deficiency?
Fat malabsorption
Long term antibiotic therapy
Breat fed new born
Infant whose mother was taking anticonvulsant therapy during pregnancy
What does bleeding timer measures?
Appropiate platelet function
How can you calculate increased bleeding time?
Blood in tube if it doesn’t coagulate in 2-9 minutes, it means long bleeding time
Which drugs can cause fat malabsorption?
Cholestyramine
Cholestypol
Which situations can cause fat malabsorption?
Drugs, Pancreatic insufficiency (CF)
Bad lipoprotein being made
Why long term antibiotics can cause vitamin K deficiency?
Because they kill the bacterias and remember a good source of vitamin K comes from bacterias
Why newborn can have vitamin K deficiency?
They don’t have gut flora, so they can not produce endogenous vitamin K
Why breast fed newborn can have vitamin K deficiency?
As newborn no gut flora
And breast milk is poor in vitamin K
Which vitamin is injected in newborn?
Vitamin K
In which process do warfarin and dicumarol interfere with?
With cotranslational modification during synthesis of the precoagulation factor
In which situations do warfarin and dicumarol prevent coagulation?
Only in vivo and cannot prevent coagulation of blood in vitro
How much time does warfarin and dicumarol take after given to a patient to see their full anticoagulant activity?
2-3 days
What is the benefit of Heparin compared to Warfarin in time?
Heparin is often given to provide short term anticoagulant activity
What is the mechanism of action of Heparin?
Activator of Antithrombin III
Coumarin, vitamin K analogs
Warfarin and Dicumarol
What vitamin is α tocopherol?
Vitamin E
How is vitamin E consider?
An antioxidant
What is the function of Vitamin E?
As a lipid compound, it is especially important for protecting other lipids from oxidative damage
It prevents perioxidation of fatty acids in cell membranes helping to maintain their normal fluidity. Incluiding LDL
What is the side effect of high blood levels of vitamin E?
Can cause hemorrhage in patient given warfarin
Vitamin E is associated with this element
Selenium
Symptoms of vitamin E deficiency
Hemolytic anemia
Acanthocytosis
CNS effects: Peripheral neuropathy, Ataxia
Retinitis pigmentosum –> blindess
CNS sites affeted in vitamin E deficiency
Dorsal column of Spinal column: Vibration, propioception
Dorsal Root ganglia: sensory path, pain
Spinocerebellar
