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CMBM Exam 2 > Vitamins > Flashcards

Vitamins Flashcards

1
Q

Thiamin major functions

A

Vitamin B1
- helps form/break C-C bonds
- Oxidative decarboxylation; Pyruvate dehydrogenase (DH); important energy yielding reactions in CHO metabolism
• Pyruvate DH → acetyl CoA
• also α-ketoglutarate DH → succinyl CoA
• Branched chain amino acid DH
- Transketolase* in pentose phosphate pathway (critical for making ribose from glucose for DNA synthesis, as well as NADPH)

  • coenzyme: thiamine pyrophosphate (TPP)
  • energy metabolism
  • synthesis of DNA, RNA, and NADPH + H+
  • nerve function
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2
Q

Thiamin deficiency

A
  • Beriberi

- Wernicke-Korsakoff syndromes

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3
Q

Riboflavin major functions

A

Vitamin B2

  • energy metabolism (redox)
  • metabolism of folate, vitamin A, niacin, vitamin B6, and vitamin K
  • neurotransmitter metabolism
  • Functions as coenzyme, e.g. part of FAD → FADH in TCA cycle
  • FMN used in electron transfer proteins
  • Cofactor for many enzymes, oxygenases, oxidoreductases
  • Can carry 2 electrons, so many enzymes which use NAD(P)H as a cosubstrate have FMN or FAD as a cofactor to accept these electrons
  • Many metalloflavoenzymes with additional metal cofactor
  • Think REDOX! Oxidation-reduction enzymes
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4
Q

Riboflavin deficiency

A
  • ariboflavinosis
    • weakness
    • cracked lips
    • dark red tongue
    • dermatitis
    • normocytic anemia
    • confusion
      – in US usually seen with alcoholism
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5
Q

Niacin major functions

A

Vitamin B3

  • 2 forms
    • nicotinic acid
    • nicotinamide
  • coenzyme (NAD+ and NADP+)
    • critical in many different pathways as electron carriers
  • energy metabolism (redox)
  • protein synthesis
  • glucose homeostasis
  • cholesterol metabolism
  • DNA repair
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6
Q

Thiamin toxicity

A

None

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7
Q

Riboflavin toxicity

A

None

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8
Q

Niacin deficiency

A
  • Pellagra (Italian for raw skin)
    • Often back of neck (Casal’s necklace)
  • Trp metabolite levels in urine suggest deficiency
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9
Q

Niacin toxicity

A

(>35 mg/day) irritation from moderately high excess

  • skin inflammation
  • flushing
  • burning of face, arms and chest, stomach

(>3000 mg/day) Long term high doses

  • liver damage
  • irreversible liver failure
  • Such doses have been used as a cholesterol lowering drug, but must be watched extremely carefully due to these side effects
  • Very useful statin alternative – acts via G protein coupled receptor, reduces lipolysis, free fatty acids, VLDLs
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10
Q

Pantothenic acid major functions

A

Vitamin B5

  • Component of Coenzyme A and acyl carrier protein (Critical for MANY functions)
  • Used to carry acyl chains (acetyl CoA, Palmitoyl CoA, etc)
  • energy metabolism
  • heme synthesis
  • cholesterol, fatty acid, steroid, and phospholipid synthesis
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11
Q

Pantothenic deficiency

A

Hard to differentiate Pantothenate deficiency from other B vitamin deficiencies

  • skin problems
  • burning feet syndrome
  • digestive problems
  • dizziness
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12
Q

Pantothenic toxicity

A

None

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13
Q

Vitamin B6

A
  • coenzyme (PLP)
  • amino acid metabolism (transamination)
  • neurotransmitter and hemoglobin synthesis
  • glycogenesis
  • regulation of steroid hormone function
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14
Q

Vitamin B6 deficiency

A
  • microcytic hypochronic anemia
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15
Q

Vitamin B6 toxicity

A
  • neurological problems
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16
Q

Biotin major functions

A
  • coenzyme
  • energy metabolism (carboxylation)
    • carboxylase reactions in Fatty acid synthesis, essential for lipid metabolism, amino acid breakdown
  • regulation of gene expression
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17
Q

Biotin deficiency

A
  • depression
  • loss of muscle control
  • skin irritations
  • impaired glucose tolerance
  • mental dysfunction
  • nausea
  • anorexia
  • dermatitis
  • many others
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18
Q

Biotin toxicity

A

None

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19
Q

Folate major functions

A
  • coenzyme (THF)
    • Tetrahydrofolate (FH4) produced from folate, is a cofactor which is the major carrier of single carbon units in the cell
  • single-carbon transfers
  • amino acid metabolism
  • DNA and RNA synthesis
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20
Q

Folate deficiency

A
  • megaloblastic anemia
    • Causes enlarged red and white blood cells; abnormal nuclear maturation, but affects other dividing cells as well
  • symptoms most common in rapidly dividing cells (RBC, intestinal epithelium, fetal tissues)
    • Associated with neural tube defects in developing embryos (starts very early, before women are aware they are pregnant)
  • Some oral contraceptives and anticonvulsants can impair absorption or increase breakdown of folate
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21
Q

Folate toxicity

A

None

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22
Q

Vitamin B12 major functions

A
  • coenzyme
    • Coenzymes participate in enzyme-catalyzed molecular rearrangements in which an H atom and a second group on the substrate exchange places
    • methylcobalamin
    • adenosylcobalamin
  • homocysteine metabolism
  • energy metabolism
  • Acts in three different enzymatic reactions:
    • Intramolecular rearrangements
    • Ribonucleotide reductase (in some bacteria)
    • Methyl group transfers (methionine synthesis from homocysteine)
  • Regenerates FH4 from methyl folate, prevents folate deficiency symptoms
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23
Q

Vitamin B12 deficiency

A
  • megaloblastic anemia
    • Causes enlarged red and white blood cells; abnormal nuclear maturation, but affects other dividing cells as well
  • Serum B12 levels fall with folate deficiency, rise when folate returns to normal
  • can cause long-term, permanent damage to myelin sheath (peripheral neuropathy)
  • ‘Pernicious anemia’ a megaloblastic anemia due to lack of intrinsic factor secretion
  • elevated homocysteine levels, which
    are linked to cardiovascular disease due to interference with collagen maturation
  • deficiency is usually made on the basis of serum or plasma vitamin B-12 concentration, with deficiency currently defined as a concentration <148 pmol/L (200 pg/mL)
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24
Q

Vitamin B12 toxicity

A

None

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25
Q

Vitamin C major functions

A
  • antioxidant
    • First thing that is oxidized in plasma under oxidative stress
  • “recharging” enzymes
  • collagen synthesis
    • Proline → hydroxyproline
    • Lysine → hydroxylysine for collagen cross-linking
  • tyrosine, neurotransmitter, and hormone synthesis
    • synthesis of adrenal hormones, carnitine, catecholamine, drug metabolism, folate metabolism, stimulates iron uptake
  • protection from free radicals
  • can regenerate reduced Vitamin E
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26
Q

Vitamin C deficiency

A
  • scurvy
    • disrupted connective tissue in muscle, skin, blood vessels
    • Hemorrhagia, bleeding gums, weakness
    • Poor wound healing, bone healing
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27
Q

Vitamin C toxicity

A
  • gastrointestinal problems
    • indigestion
  • hypoglycemia
  • kidney stones
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28
Q

Choline major functions

A
  • phospholipid synthesis
    • in phospholipids, methyl donor
  • neurotransmitter synthesis
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29
Q

Choline deficiency

A
  • liver damage
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30
Q

Choline toxicity

A
  • fishy body odor
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31
Q

Vitamin-like compounds

A
  • inositol
  • choline
  • lipoic acid
  • PQQ- pyrroloquinoline quinone
32
Q

Lipoic acid

A
  • not a vitamin, but required for pyruvate decarboxylase

- animals can make this

33
Q

PQQ – Pyrroloquinoline quinone

A

methoxatin

- a redox cofactor for quinoproteins (like flavoproteins – dehydrogenases) possibly a vitamin – not sure yet

34
Q

Vitamin deficiencies: Primary deficiency

A

lack of adequate intake in diet
- Typical causes: poor nutrition/food habits, poverty, ignorance of
nutrition needs, insufficient food, lack of proper (vitamin-rich) foods, food fads, food taboos, vitamin destruction (storage, cooking), anorexia

35
Q

Vitamin deficiencies: Secondary deficiency

A

Poor availability or utilization of a vitamin due to environmental or physiological conditions
- Typical causes: poor digestions (achlorhydria; low gastric acid), malabsorption (diarrhea, infections), impaired utilization (drug therapy)

Even in developed world risk of vitamin deficiencies significant in:
• Any patient with digestion/malabsorption problems
• Chronic substance abuse (alcohol) bad diet inhibits uptake of vits
• Recent surgery, total parenteral nutrition
• Elderly, pregnant/breastfeeding, smokers, alcoholics, diabetics
• Some more specific, e.g. risk thiamine deficiency with high CHO diet

36
Q

Small amounts of what vitamins are made by bacteria in the terminal part of the small intestine and in the large intestine?

A
  • vitamin K
  • vitamin B12
  • biotin
37
Q

Vitamin A major functions

A
  • growth
  • reproduction
  • vision
  • cell differentiation
  • immune function
  • bone health
38
Q

Vitamin A deficiency

A

serum levels < 0.7 umol/L)

  • night blindness
  • xeropthalmia
  • hyperkeratosis

world-wide health problem
- affects 20-35% of all child mortality
(increased susceptibility to infection)
- supplementation alone can reduce preschool mortality 23-34% in developing countries
- Blinds 250,000 - 500,000 preschool children per year in developing countries
- Can worsen iron status, causing anemia
- Accompanies protein and Zinc malnutrition
- supplementation enhances effects of vaccines

39
Q

Vitamin A toxicity

A
  • blurred vision
  • birth defects (teratogenic)
  • liver damage
  • osteoporosis
  • headache
  • nausea
  • skin irritation
  • pain in joints

Retin A topical treatment for acne, Accutain (oral) – both can cause birth defects – this is retinoid toxicity
* risk can persist several months after stopping drug

40
Q

Vitamin D major functions

A
  • calcium homeostasis
  • bone health
  • cell differentiation
  • may modulate inflammation/ immune responses
41
Q

Vitamin D deficiency

A

serum 25-hydroxyvitamin D (25-OHD) concentration is less than 20 ng/mL

  • rickets
  • osteomalacia
  • osteoporosis
  • linked to type II diabetes, autoimmune diseases, and other chronic diseases (cardiovascular, cancer, etc)
  • Not a serious problem until industrialization of Europe (not enough exposure to sunlight)
42
Q

Vitamin D toxicity

A
  • hypercalcemia (deposition of Ca in soft tissues)

- large excesses can be lethal, there can be local tissue ‘intoxication’

43
Q

Vitamin E major functions

A
  • antioxidant
    • Vitamin E (α-tocopherol); A reducing reagent that scavenges oxygen and free radicals
    • LDLs contain significant amounts of Vitamin E to protect them from oxidation
  • cell membranes
  • eye health
  • heart health
44
Q

Vitamin E deficiency

A
  • neurological problems
    • rate depends on levels of ROS
    • neuromuscular problems; deficiency can lead to ataxia virtually identical to Freidreich’s ataxia
    • peripheral neuropathy
  • hemolytic anemia
  • retinitis pigmentosa
45
Q

Vitamin E toxicity

A
  • hemorrhage
  • Unlike other fat-soluble vitamins, E does not accumulate in liver to toxic levels
    • oxidized by ω-oxidation by cytochrome P450’s, as if it were a xenobiotic, conjugated and excreted in urine or bile
    • sebaceous glands secrete E to protect cutaneous lipids
46
Q

Vitamin K major functions

A
  • Critical role in gene regulation (including reproduction, embryogenesis, development, cell differentiation and proliferation)
  • Required for post-translational modification of many proteins which bind Ca++, including blood-coagulating proteins
  • cofactor (carboxylation)
    • carboxylases which add a gamma-carboxy group (an extra COO-) onto glutamates
  • blood clotting
  • bone health
  • tooth health
47
Q

Vitamin K deficiency

A
  • Vitamin K deficiency bleeding ( VKDB)
48
Q

Vitamin K toxicity

A
  • no known effects
49
Q

Vitamin A derived from

A
  • carotenoids

- plant pigments, e.g. β-carotene

50
Q

Vitamin A 3 forms

A
  • alcohol
  • aldehyde
  • acid
51
Q

Retinol

A
  • derived from vitamin A

- absorbed by rod cell in form of retinol binding protein

52
Q

Vitamin A RDA

A
  • 900 ug/day for men
  • 700 ug/day women
    • Usually expressed as “retinol activity equivalents” or RAE
53
Q

Vitamin D biosynthesis

A
  • a mixture of ergocalciferol (D2) and cholecalciferol (D3) in food
  • Derived from cholesterol-
    synthesized in skin when UV light is present
  • Liver converts D3 to 25-hydroxyvitamin D, kidneys then convert to 1,25-dihyroxyvitamin D (Calcitrol), the active form
    • an -OH group is added at carbon 25
  • Regulates Phosphorus and Ca levels in body
    • increases Ca uptake from diet, decreases Ca loss in urine, facilitates release of Ca from bones
54
Q

Vitamin D RDA

A
  • 10 ug/day (Children and adults)
  • 15 ug/day (age 51)
  • 20 ug/day (age 71)
55
Q

Vitamin K inhibitors

A
  • Coumarin / Wafarin
    • Coumarin in low doses (4-5 mg/day) inhibits vitamin K epoxide reductase and Vit K reductase – depletes Vit K
      and inhibits enzymes requiring this, ultimately blood clotting
    • Coumarin useful for patients with risk of deleterious blood clots
    • Wafarin (high concentration of the same stuff!) is used as a rodenticide

+ Hemorrhagic disease in cattle eating sweet clover hay – discovered Dicumarol (inhibited clotting)

56
Q

Water soluble vitamins

A 
- B Vitamins 
• Thiamine (Vitamin B1) 
• Riboflavin (B2) 
• Niacin (B3) 
• Pantothenic acid (B5) 
• Pyridoxine (Pyridoxal, pyridoxamine) (B6) 
• Cobalamin (B12) 
- Biotin (vitamin H) 
- Folic acid 
- Vitamin C (Ascorbic acid)
57
Q

Thiamine RDA

A
  • ~1.2 mg/day
58
Q

Berberi

A
  • Insufficient ATP production, decreased synthesis of DNA, RNA, proteins, fatty acids
  • Muscle tissue wasting, cardiovascular damage (often cause of death in beriberi)
  • CNS damage – confusion, loss of reflex
  • Edema
  • Occurs in sailors on meatless diets or polished rice
  • Currently seen in chronic alcoholism
59
Q

Wernicke-Korsakoff syndromes

A
  • Wernicke syndrome – usually associated with chronic alcoholism
    • Why? Poor diet, but also ethanol inhibits thiamine uptake
  • Known as ‘dry BeriBeri’, but progresses to ‘wet’ form as develop cardiac dilated hypermyopathy (loss of energy, fluid buildup)
    • pretty much reversible with supplementation (but how much to give? Not clear)
  • Severe deficiency involved CNS, Korsakoff encephalopathy (but since Wernicke already in place Wernicke-Korsakoff (WK) syndrome)
    • short term memory loss (irreversible)
  • Some people genetically predisposed to WK syndrome when diet is thiamine deficient, possibly due to mutation in tranketolase, but cause so far unclear
60
Q

Riboflavin

A
  • heat stable part of whey extract

- Intense yellow-green fluorescence

61
Q

Riboflavin RDA

A

~1.2 mg/day

- we store about 1-2 weeks worth, so regular uptake is important

62
Q

Niacin RDA

A
  • expressed as milligram niacin equivalents (NE)
    • corresponds to 1 mg pure niacin or 60 mg tryptophan (only a small amount of Trp will be made into niacin)
  • 16 mg NE/day, men
  • 14 mg NE/day, women
63
Q

Pellagra symptoms (severe)

A

Niacin deficiency

  • Fatigue
  • headache
  • apathy
  • depression
  • memory loss
  • dementia
  • pigmented skin rash after sun exposure
  • vomiting
  • diarrhea

+ Some diseases like Hartnup disease impair Trp absorption, can lead to niacin deficiency

64
Q

Pyridoxine

A
  • B Vitamin
  • A family of compounds – involved in > 100 transamination, decarboxylation and other reactions in the cell
    • required for function of glycogen phosphorylase (glycogenolysis), synthesis of heme, γ-aminobutyric acid
65
Q

Pyridoxal Phosphate (PLP)

A
  • Vitamin B6 is phosphorylated to form PLP
  • PLP is a prosthetic group for enzymes catalyzing reactions involving amino acid metabolism (isomerizations, decarboxylations, side chain eliminations or replacements)
  • deficiencies lead to dermatitis and disorders of protein metabolism)
66
Q

Pyridoxine RDA

A

~1.3 mg/day

- Store about 110 mg (men) 60 mg (women) in muscle, half-life about 25 days

67
Q

Pyridoxine deficiency

A
  • microcytic anemia
  • EEG abnormalities
  • epileptic seizures
  • depression
  • confusion
  • seborrheic dermatitis
  • possibly platelet and clotting problems

Some drugs such as penicillinamine or isozianid (for treatment of cystinuris,
or rheumatoid arthritis) can bind to pyridoxal/PLP, creating deficiency

68
Q

Pyridoxine toxicity

A
  • may cause peripheral neuropathy
  • dermatological lesions
  • May interact with some drug therapy (levodopa, phenobarbital, Dilantin)
69
Q

Biotin RDA

A
  • unclear; 30 ug/day
    adequate intake
  • Some anticonvulsants inhibit uptake (e.g. carbamazepine)
70
Q

Vitamin B12 structure

A
  • Cobalamin contains a corrin ring system and a cobalt (it is synthesized by only a few microorganisms)
71
Q

Vitamin B12 RDA

A
  • Most ‘potent’ vitamin known (required in smallest amounts)
    adult humans require about 3 ug/day
  • metformin impairs B12 uptake
72
Q

Homocysteine

A
  • made by removing terminal –CH from Methionine
  • It can be reconverted back to Met using Tetrahydrofolate + B12
  • Or it can be converted to Cys using B6 (pyridoxine)
  • elevated serum levels of Hcy can be indicative of low B6, B12, or THF
73
Q

Intrinsic Factor (IF)

A
  • secreted from parietal cells in response to hormones
  • B12 can ONLY be absorbed in intestines when complexed to IF
  • IF-B12 binds to a specific receptor in the ileum and absorbed
  • Liver stores about 2-2.5 mg – can last 6-10 years in absence of B12 in diet
74
Q

Folate RDA

A
  • 3 ug/kg/day
  • 200 ug for men
  • 180 ug for women (400 ug for pregnant women)
  • long cooking can destroy 90% in food
75
Q

Vitamin E

A
  • 15 mg/day
    • many Americans may only get about 8 mg/day
  • Only plants can make vitamin E
76
Q

Vitamin C RDA

A
  • 10 mg/day prevents scurvy minimally
  • ~ 60 mg/day to fully saturate tissue
  • Approximately 200 mg/day is saturating

CMBM Exam 2 (13 decks)

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