Flashcards in FA - Biochemistry - Nutrition Deck (85):
Why are the fat soluble vitamins more commonly toxic than the water-soluble vitamines?
Because fat-soluble vitamins accumulate in fat.
What is another name for B1?
What is another name for B2?
Riboflavin: FAD, FMN
What is another name for B3?
What is another name for B5?
Pantothenic acid: CoA.
What is another name for B6?
What is another name for B7?
What is another name for B9?
What is another name for B12?
What are the 3 common features of B-complex deficiencies?
What is the function of vitA?
2. Constituent of visual pigments (retinal)
3. Essential for normal differentiation of epithelial cells into specialized tissue (pancreatic, mucus-secreting cells).
4. Prevents squamous metaplasia.
5. Used to treat measles.
6. Used to treat AML-M3
What is another name for vitA?
Where is vitA found?
In liver + leafy vegetables.
What happens with vitA deficiency?
1. Night blindness (nyctalopia)
2. Dry, scaly skin (xerosis cutis)
3. Corneal degeneration (keratomalacia)
5. Bitot spots on conjunctiva.
What happens in vitA excess?
2. Skin changes (scaliness)
4. Cerebral edema
5. Pseudotumor cerebria
7. Hepatic abnormalities
Is vitA contraindicated in pregnancy?
YES - Teratogenic --> cleft palate, cardiac abnormalities.
A (-) pregnancy test and 2 FORMS contraception are needed before isotretinoin is prescribed for SEVERE CYSTIC ACNE.
What is the function of thiamine (B1)?
In thiamine pyrophosphate (TPP) --> Cofactor for several dehydrogenase enzyme reactions:
1. Pyruvate dehydrogenase (links glycolysis to TCA cycle)
2. α-ketoglutarate dehydrogenase (TCA cycle)
3. Transketolase (HMP shunt)
4. Branched-chain ketoacid dehydrogenase
Mention some conditions associated with thiamine deficiency (B1)?
2. Dry beriberi
3. Wet beriberi
What are the features of Wernicke-Korsakoff syndrome?
3. Ataxia (classic triad)
5. Personality change
6. Memory loss (permanent)
==> Damage to MEDIAL DORSAL NUCLEUS OF THALAMUS + MAMILLARY BODIES.
What are the features of dry beri beri?
2. Symmetrical muscle wasting
What are the features of wet beriberi?
1. High-output cardiac failure (DCM)
What happens in thiamine deficiency?
Impaired glucose breakdown --> ATP depletion worsened by glucose infusion.
==> Highly aerobic tissues (e.g., brain, heart) are affected first.
How is the diagnosis of thiamine (B1) deficiency made?
By increased in RBC transketolase activity following B1 administration.
What is the function of riboflavin (B2)?
Component of flavins FAD and FMN, used as cofactors in redox reactions, e.g., the succinate dehydrogenase reaction in the TCA cycle.
What happens in riboflavin (B2) deficiency?
1. Cheilosis - inflammation of lips, scaling and fissures at the corners of the mouth.
2. Corneal vascularization.
What is the function of niacin (B3)?
1. Constituent of NAD+, NADP+ (used in redox reactions).
2. Derived from tryptophan.
3. Synthesis requires B2 and B6.
4. Used to treat dyslipidemia
5. Lowers levels of VLDL and raises levels of HDL.
What happens in niacin (B3) deficiency?
2. Severe deficiency leads to pellagra
What may cause pellagra?
1. Hartnup disease (decr. tryptophan absorption).
2. Malignant carcinoid syndrome (incr. tryptophan metabolism).
3. Isoniazid (decr. vitB6).
What are the symptoms of pellagra?
2. Dementia (also hallucinations)
3. Dermatitis --> e.g., C3/C4 dermatome circumferential "broad collar" rash [Casal necklace] + HYPERPIGMENTATION of sun-exposed limbs.
What happens in niacin excess?
1. Facial flushing (induced by prostaglandin, NOT histamine ==> Can avoid by taking ASPIRIN).
What is the function of pantothenate (B5)?
Essential component of CoA + fatty acid synthase.
What happens in pantothenate (B5) deficiency?
4. Adrenal insufficiency
What is the function of pyridoxine (B6)?
Converted to pyridoxal phosphate (PLP), a cofactor used in:
1. TRANSAMINATION (e.g., ALT and AST).
2. Decarboxylation reactions.
3. Glycogen phosphorylase.
What is the synthetic role of pyridoxine (B6)?
What happens in pyridoxine deficiency (B6)?
3. Peripheral neuropathy --> Deficiency inducible by isoniazid + OCPs.
4. Sideroblastic anemias due to impaired Hb synthesis + iron excess.
What is the function of biotin (B7)?
Cofactor for CARBOXYLATION enzymes (which add a 1-carbon group):
1. PYRUVATE CARBOXYLASE: pyruvate (3C) --> oxaloacetate (4C).
2. ACETYL-CoA CARBOXYLASE: acetyl-CoA (2C) --> malonyl-CoA (3C).
3. PROPIONYL-CoA CARBOXYLASE: propionyl-CoA (3C) --> methylmanonyl-CoA (4C).
What are the features of biotin deficiency (B7)?
What may cause biotin deficiency (B7)?
2. Excessive ingestion of RAW EGG WHITES.
What is the function of folate (B9)?
1. Converted to THF - coenzyme for 1-carbon transfer/methylation reactions.
2. Important for the synthesis of nitrogenous bases in DNA and RNA.
Where is folate absorbed?
In the jejunum.
What are the features of folate deficiency (B9)?
1. Macrocytic, megaloblastic anemia
2. Hypersegmented PNMs
4. No neurologic symptoms
What are the lab findings in folate (B9) deficiency?
1. Incr. Homocysteine
2. Normal methylmalonic acid
What is the MC vit deficiency in the US?
Folate deficiency --> Seen in alcoholism + pregnancy.
Mention some drugs that may cause folate deficiency.
Why is it important to give supplemental maternal folic acid in early pregnancy?
Decr. risk of neural tube defects.
What is the function of B12?
1. Cofactor for METHIONINE SYNTHASE - transfers CH3 groups as methylcobalamin.
1. Cofactor for methylmalonyl-CoA mutase.
What are the features of B12 deficiency?
1. Macrocytic, megaloblastic anemia.
2. Hypersegmented PMNs
4. Subacute combined degeneration (degeneration of dorsal columns, lateral corticospinal tracts, and spinocerebellar tracts) --> due to abnormal myelin.
With what lab findings is B12 deficiency associated?
1. Incr. serum homocysteine
2. Methylmalonic acid levels
What is the problem with prolonged B12 deficiency?
IRREVERSIBLE nerve damage.
What is the function of vitC?
2. Also facilitates iron absorption by reducing it to Fe2+ state.
For what reactions is vitC essential?
1. Hydroxylation of PROLINE and LYSINE in COLLAGEN synthesis.
2. Necessary for dopamine β-hydroxylase, which converts dopamine to NE.
In what condition is vitC used as ancillary treatment?
For methemoglobinemia by reducing Fe3+ to Fe2+.
What happens in vitC deficiency (scurvy)?
1. Swollen gums
5. Poor wound healing
6. Perifollicular + subperiosteal hemorrhages
8. Weakened immune hemorrhage
What happens in vitC excess?
5. Calcium oxalate nephrolithiasis
--> Can increase risk in predisposed individuals (e.g., those with transfusions, hereditary hemochromatosis).
What is vitD2?
Ergocalciferol --> ingested from plants.
What is vitD3?
Cholecalciferol --> consumed in milk - formed in sun-exposed skin (stratum basale).
What is the storage form of vitD?
25-OH D3 = storage form.
What is the active form of vitD?
What is the function of vitD?
1. Intestinal absorption of calcium and phosphate.
2. Incr. bone mineralization AT LOW LEVELS.
3. Incr. bone RESORPTION AT HIGH LEVELS.
What exacerbates vitD deficiency?
1. Low sun exposure
2. Pigmented skin
What happens in vitD excess?
3. Loss of appetite
5. Seen in GRANULOMATOUS DISEASES (Incr. activation of vitD by epithelioid macrophages).
What is the function of vitE (tocopherol/tocotrienol)?
Antioxidant --> protects erythrocytes and membranes from free radical damage.
E for Erythrocytes.
Of what anticoagulant can vitE enhance its effects?
What happens in vitE deficiency?
1. Hemolytic anemia
3. Muscle weakness
4. Posterior column + spinocerebellar tract demyelination
What is important to keep in mind about vitE deficiency?
Neurological presentation may appear similar to vitB12 deficiency, but WITHOUT:
1. Megaloblastic anemia
2. Hypersegmented neutrophils
3. Incr. serum methylmalonic acid levels
What is the function of vitK?
Cofactor for the γ-carboxylation of glutamic acid residues on various proteins required for blood clotting.
==> Synthesized by intestinal flora.
What happens in vitK deficiency?
1. Neonatal hemorrhage with incr. PT and incr. aPTT but normal bleeding time --> neonates have STERILE intestines and are unable to synthesize vitK.
2. Can also occur after prolonged use of broad-spectrum antibiotics.
Is there vitK in breast milk?
Not in breast milk; neonates are given vitK injection at birth to prevent HEMORRHAGIC DISEASE OF THE NEWBORN.
What is the function of zinc?
Essential for the activity of 100+ enzymes --> Important in the formation of zinc fingers (transcription factor motif).
What happens in zinc deficiency?
1. Delayed wound healing
3. Decr. adult hair (axillary, facial, pubic)
6. ACRODERMATITIS ENTEROPATHICA
==> May predispose to ALCOHOLIC cirrhosis
What is the limiting reagent in ethanol metabolism?
Which are the 2 main enzymes involved in alcohol metabolism?
1. Alcohol dehydrogenase
2. Acetaldehyde dehydrogenase
What kinetics does alcohol dehydrogenase utilize?
Ethanol increases NADH/NAD+ ratio in liver. What does this cause?
1. Pyruvate --> lactate (lactic acidosis).
2. Oxaloacetate --> malate (prevents gluconeogenesis --> fasting hypoglycemia).
3. Dihydroxyacetone phosphate --> Glycerol-3-phosphate (combines with fatty acids to make triglycerides --> Hepatosteatosis).
What else does increased NADH/NAD+ ratio do?
Disfavors TCA production of NADH --> Incr. utilization of acetyl-CoA for KETOGENESIS (-->ketoacidosis) + LIPOGENESIS (--> hepatosteatosis).
What is the action of fomepizole?
Inhibits alcohol dehydrogenase --> ANTIDOTE for methanol or ethylene glycol poisoning.
What is the action of disulfiram?
Inhibits acetaldehyde dehydrogenase --> acetaldehyde accumulates, contributing to hangover symptoms.
What happens in Kwashiorkor?
Protein malnutrition resulting in:
1. Skin lesions
2. Edema ==> Decr. plasma oncotic pressure.
3. Liver malfunction (fatty change due to decr. apolipoprotein synthesis)
==> Picture is small child with swollen belly.
What is the mnemonic for Kwashiorkor?
What happens in Marasmus?
Total calorie malnutrition resulting in EMACIATION:
1. Tissue + Muscle wasting.
2. Loss of subcutaneous fat
3. +/- edema.
MINERAL OIL INTAKE may cause ...?
FAT-SOLUBLE vitamin deficiencies.
VitA - Excess - Acute toxicity:
4. Blurred vision.
Vit A - Excess - Chronic toxicity:
2. Dry skin (eg scaliness).
3. Hepatic toxicity + Enlargement.
5. Pseudotumor cerebri.
==> Deficiency of neutral amino acids (eg tryptophan) TRANSPORTERS in proximal renal tubular cells + ON ENTEROCYTES ==> Neutral aminoaciduria + Decr. absorption from the GUT ==> Decr. tryptophan for conversion to NIACIN ==> PELLAGRA-LIKE SYMPTOMS.