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
2
Q
Thiamin deficiency
A
- Beriberi
- Wernicke-Korsakoff syndromes
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
4
Q
Riboflavin deficiency
A
- ariboflavinosis
- weakness
- cracked lips
- dark red tongue
- dermatitis
- normocytic anemia
- confusion
– in US usually seen with alcoholism
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
6
Q
Thiamin toxicity
A
None
7
Q
Riboflavin toxicity
A
None
8
Q
Niacin deficiency
A
- Pellagra (Italian for raw skin)
- Often back of neck (Casal’s necklace)
- Trp metabolite levels in urine suggest deficiency
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
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
11
Q
Pantothenic deficiency
A
Hard to differentiate Pantothenate deficiency from other B vitamin deficiencies
- skin problems
- burning feet syndrome
- digestive problems
- dizziness
12
Q
Pantothenic toxicity
A
None
13
Q
Vitamin B6
A
- coenzyme (PLP)
- amino acid metabolism (transamination)
- neurotransmitter and hemoglobin synthesis
- glycogenesis
- regulation of steroid hormone function
14
Q
Vitamin B6 deficiency
A
- microcytic hypochronic anemia
15
Q
Vitamin B6 toxicity
A
- neurological problems
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
17
Q
Biotin deficiency
A
- depression
- loss of muscle control
- skin irritations
- impaired glucose tolerance
- mental dysfunction
- nausea
- anorexia
- dermatitis
- many others
18
Q
Biotin toxicity
A
None
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
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
21
Q
Folate toxicity
A
None
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
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)
24
Q
Vitamin B12 toxicity
A
None
25
Vitamin C major functions
- 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
26
Vitamin C deficiency
- scurvy
* disrupted connective tissue in muscle, skin, blood vessels
* Hemorrhagia, bleeding gums, weakness
* Poor wound healing, bone healing
27
Vitamin C toxicity
- gastrointestinal problems
* indigestion
- hypoglycemia
- kidney stones
28
Choline major functions
- phospholipid synthesis
* in phospholipids, methyl donor
- neurotransmitter synthesis
29
Choline deficiency
- liver damage
30
Choline toxicity
- fishy body odor
31
Vitamin-like compounds
- inositol
- choline
- lipoic acid
- PQQ- pyrroloquinoline quinone
32
Lipoic acid
- not a vitamin, but required for pyruvate decarboxylase
| - animals can make this
33
PQQ – Pyrroloquinoline quinone
methoxatin
| - a redox cofactor for quinoproteins (like flavoproteins – dehydrogenases) possibly a vitamin – not sure yet
34
Vitamin deficiencies: Primary deficiency
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
Vitamin deficiencies: Secondary deficiency
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
Small amounts of what vitamins are made by bacteria in the terminal part of the small intestine and in the large intestine?
- vitamin K
- vitamin B12
- biotin
37
Vitamin A major functions
- growth
- reproduction
- vision
- cell differentiation
- immune function
- bone health
38
Vitamin A deficiency
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
Vitamin A toxicity
- 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
Vitamin D major functions
- calcium homeostasis
- bone health
- cell differentiation
- may modulate inflammation/ immune responses
41
Vitamin D deficiency
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
Vitamin D toxicity
- hypercalcemia (deposition of Ca in soft tissues)
| - large excesses can be lethal, there can be local tissue ‘intoxication’
43
Vitamin E major functions
- 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
Vitamin E deficiency
- 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
Vitamin E toxicity
- 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
Vitamin K major functions
- 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
Vitamin K deficiency
- Vitamin K deficiency bleeding ( VKDB)
48
Vitamin K toxicity
- no known effects
49
Vitamin A derived from
- carotenoids
| - plant pigments, e.g. β-carotene
50
Vitamin A 3 forms
- alcohol
- aldehyde
- acid
51
Retinol
- derived from vitamin A
| - absorbed by rod cell in form of retinol binding protein
52
Vitamin A RDA
- 900 ug/day for men
- 700 ug/day women
* Usually expressed as “retinol activity equivalents” or RAE
53
Vitamin D biosynthesis
- 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
Vitamin D RDA
- 10 ug/day (Children and adults)
- 15 ug/day (age 51)
- 20 ug/day (age 71)
55
Vitamin K inhibitors
- 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
Water soluble vitamins
```
- 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
Thiamine RDA
- ~1.2 mg/day
58
Berberi
- 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
Wernicke-Korsakoff syndromes
- 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
Riboflavin
- heat stable part of whey extract
| - Intense yellow-green fluorescence
61
Riboflavin RDA
~1.2 mg/day
| - we store about 1-2 weeks worth, so regular uptake is important
62
Niacin RDA
- 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
Pellagra symptoms (severe)
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
Pyridoxine
- 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
Pyridoxal Phosphate (PLP)
- 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
Pyridoxine RDA
~1.3 mg/day
| - Store about 110 mg (men) 60 mg (women) in muscle, half-life about 25 days
67
Pyridoxine deficiency
- 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
Pyridoxine toxicity
- may cause peripheral neuropathy
- dermatological lesions
- May interact with some drug therapy (levodopa, phenobarbital, Dilantin)
69
Biotin RDA
- unclear; 30 ug/day
adequate intake
- Some anticonvulsants inhibit uptake (e.g. carbamazepine)
70
Vitamin B12 structure
- Cobalamin contains a corrin ring system and a cobalt (it is synthesized by only a few microorganisms)
71
Vitamin B12 RDA
- Most ‘potent’ vitamin known (required in smallest amounts)
adult humans require about 3 ug/day
- metformin impairs B12 uptake
72
Homocysteine
- 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
Intrinsic Factor (IF)
- 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
Folate RDA
- 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
Vitamin E
- 15 mg/day
* many Americans may only get about 8 mg/day
- Only plants can make vitamin E
76
Vitamin C RDA
- 10 mg/day prevents scurvy minimally
- ~ 60 mg/day to fully saturate tissue
- Approximately 200 mg/day is saturating
