Vitamins Flashcards
1
Q
Vitamin Deficiencies
A
result from inadequate supply
2
Q
Vitamin Insufficiencies or vitamin Dependencies result from
A
result from abnormal
metabolism with an adequate supply
3
Q
Vitamin toxicity ( Fat soluble) can result if
A
can result if over-ingested
4
Q
Vitamins physiological functions
A
- Serve primarily as cofactors of enzymatic
reactions in body - Some function as hormones (Vit A & D)
- Some function as transcription regulators (Vit A)
** Must be obtained from external sources
5
Q
Vitamins that serve as transcription factors
A
Vitamin A
6
Q
Vitamins that serve as hormones
A
Vit A and D
7
Q
Vitamins metabolism
A
1.Reduced serum levels may not indicate a
deficiency that interrupts cellular function
2.Normal values may not reflect adequate function
2A) Clinical expression of Vit abnormalities
2B) Clinical symptoms of Vit deficiencies: nonspecific
in early as well as in mild chronic stages
➡ Deficiencies difficult to diagnose initially
8
Q
Fat soluble vitamins
A
A, E, D, K
9
Q
Water soluble vitamins
A
B vitamins: thiamine, riboflavin,
niacin, B6, B12,
folate, pyridoxine,
pantothenic acid &
others
➢Biotin
➢Vitamin C
➢Carnitine
10
Q
Laboratory measurements of vitamins
A
➢ vitamin precursors
➢ vitamin
➢ vitamin metabolites
➢ some biochemical function with and
without vitamin (Schilling, etc.)
Blood (serum/plasma) or urine
* Immunoassay, HPLC, CPB
- RIA, MEIA, and FPIA
11
Q
Immunoassays of vitamins
A
HPLC, CPB
RIA, MEIA, FPIA
12
Q
FAT soluble vitamins
types
Absorbed as part of
what must be present for Absorption
what conditions are they deficient
A
-A,D,E,K
-Absorbed as part of the chylomicron
* Fat must be present for absorption
* Chronic malabsorptive states
13
Q
Fat soluble Vitamins come from what sources and where are they stored
A
Dietary sources
animal & plant products—varies with
vitamin
Stored in liver and fat tissue
14
Q
Deficiencies of fat soluble vitamins
Vitamin A, E, and D+K storage
May be difficult to
A
Deficiencies: develop slowly
- Vit A storage: 1 year
- Vit E storage: several months
- Vit D & K: storage days or weeks
may be difficult to diagnose; vague symptoms
15
Q
Fat soluble vitamins disorders
A
Bile and pancreatic function,
bowel mucosa
mpaired bile flow,
* Pancreatic disease
* Chronic bowel inflammatory conditions
* Fistula
* Small bowel obstruction
* Alcohol liver disease
* Cryptosporidium infection
16
Q
New acquired form of lipid soluble vit deficiency
- A,D,E,K
A
✴ Lipase inhibitor: Xenical
✴ Ingestion of non-bioavailable fat substitutes: Olester
✴ Patient after bilopancreatic diversion for obesity
17
Q
Water soluble vitamins
At least how many water soluble vitamins
Moderate excess intake is
Most are stored for
Deficiencies develop more rapid then
A
- At least 9 water soluble vitamins
- Moderate excess intake is almost immediately excreted in the urine
- Most are stored for <2 months
➢Deficiencies develop more rapidly than fat soluble vitamin
deficiencies
18
Q
Exceptions is vitamin
A
-B-12
-can be stored in the liver for up to 12 months.
19
Q
Vitamin A
has how many active forms and what are there names
* Derived from dietary carotenoids (β-carotene)
A
Three biologically active forms
➢Retinol, Retinal, Retinoic acid
20
Q
Vitamin A dietary source
A
➢animal and plant
➢butter, al-livcream, whole milk, whole milk
cheeses, egg yolk
➢dark green leafy vegetables, yellow vegetables,
yellow fruit & fortified margarine
21
Q
Retinol is carried by
A
Chylomicrons in the lymphatics to the liver where retinol binds to RBP and pre-Albumin
Retinol + RBP/ Pre-albumin attaches to RBP-receptor and allows Retinol + cRBP into the cell.
22
Q
Functions of vitamin A
A
➢Vision (most clearly defined role)
➢Growth
➢Reproduction
➢Mucus secretion
➢Immune system functions
➢Epithelial cell development, differentiation,
regulation.
23
Q
Vitamin E: Tocopherol has several isomers but
A
a form is most studied
24
Q
Vitamin E: Tocopherol dietary sources
A
➢Vegetables oils
➢Wheat germ, rice germ,
➢Leafy green vegetables,
➢Legumes & nuts
* Transported: w/ chylomicrons &
VLDL (aTTP)
* Stored primarily in adipose tissue
25
Vitamin E: Tocopherol functions
➢Antioxidant
➢Protects cell membrane (RBC) from
oxidation of lipids in the membrane.
➢Therapeutically to prevent hemolytic
anemia. (premature newborns)
➢Anti-aging, cardio and neuro protection
26
Vitamin K: hydroquinone
has several structures and they are
K1, K2, K3
27
Vitamin K Dietary sources
➢cabbage, cauliflower, green leaves of
alfalfa, spinach, liver, soy beans and
vegetable oil.
➢Intestinal bacteria
--> 50% from each source
*Absorption is with chylomicrons
28
Vitamin K (hydroquinone) functions
* Normal coagulation
➢Required for synthesis of Factor II, VII, IX,
X, protein C & S
✓Acts as a cofactor in Vit-K dependent
carboxylation of glutamic acid
29
Vitamin K1 is
Phylloquinone
30
Vitamin K2
Menaquinone-4
31
Vitamin K3
Menadione
32
Two forms of Vit D
Vitamin D3= cholecalciferol
Vitamin D2= Calciferol
33
Vitamin D3
➢Produced in skin from UV
activation of 7-dehydrocholesterol
➢Prohormone converted by liver to calcidiol
à hydroxylated to calcitriol (active form
34
Vitamin D2
*Vit D 2 : calciferol (dietary form)
➢Hydroxylated to calcitriol in the same way as D
35
Dietary sources of Vitamin D
➢Fish liver oil
➢Fortified milk
➢Irradiated foods
( Ionizing Radiation)
➢Smaller amounts in butter, egg yolk, liver, certain fish (esp. salmon and sardin
36
Vitamin D functions
➢Calcitriol enhances Ca2+ uptake from the GI and increases the release of Ca2+ from
bone into blood
37
Vitamin A deficiency lead to
Decreased vision and Decreased Immune system function
38
Vitamin A toxicity
---> upon what
symptoms
Upon overdose
❑ Symptoms:
* Dermatologic disorders
* Bone pain
* Renal disorders
* Intracranial
hypertension
* Hemorrhage
* Teratogen
39
Total Vitamin A assay
Retinol(RBP) assay
B-Carotene
* Total Vit A:
➡Fluorometry or HPLC
* Retinol (RBP):
➡Immunoassay
* β-Carotene:
➡Extraction of β-carotene,
* measure directly @ 450 nm
** Light sensitive
40
Vitamin E Deficiency
* Rare
* Neurological signs
- Ataxia
- Peripheral neuropathy
* Macrocytic megaloblastic Anemia
41
Vitamin E Assay
* HPLC
* GC-IDMS
* Photometry or Fluorimetry
* TLCG
à separate tocopherols &
tocotrienols.
42
Vitamin E assay reaction
Tocopherol + FeCl3
-----> Tocopheryl quinine + Fe2+ + a,a-dipyridyl [ Red].
43
Vitamin K deficiency
* ~ 3 weeks to develop
* Hemorrhage secondary to reduced
prothrombin and other coagulation factors
* ecchymoses, epitaxis, intestinal
hemorrhage
44
Vitamin K Assay
* Seldom measured directly
* PT & APTT
à Both will be prolonged in a deficiency,
but thrombin time will be normal
* Direct measurement:
immunoassay or HPLC (rare)
45
Vitamin D deficiency
* bone malformations
--> à Rickets in children and osteomalacia in adults
46
Vitamin D Assays
* Immunoassay
* HPLC
* LC with Mass Spec (LCMS)
** Normal values still being debated
* <50 nmol/L considered low
47
water soluble vitamins
Vitamin C and B
48
Vitamin C
-Distributed throughout what
- Deficiency may take several blank to
- High concentrations in
- Excreted in urine as blank
* Distributed throughout tissues
* Deficiency may take several months to develop symptoms
* High concentration in CSF
* Excreted in urine as oxalate
49
Plasma Vitamin C concentration is lower then
CSF
50
Oxalate is the metabolite of
Oxalate is the metabolite of Vitamin C --~50% of urinary oxalate is from
Vitamin C
51
Ascorbic Acid dietary sources
-Found primarily in citrus fruits & vegetables: oranges, lemons, limes,
tomatoes, grapefruit
- Other vegetables and fruits: green peppers, broccoli, leafy green vegetables, potatoes,
strawberries
-Heat and oxygen labile
52
Vitamin C is high in what foods
found primarily in citrus fruits & vegetables: oranges, lemons, limes,
tomatoes, grapefruit
Highest in those foods when they are fresh & uncooked
53
Many plants and animals can synthesize what but humans cant
Plants and many other animals can synthesize Vitamin C, but humans cannot—
must be ingested.
Protein and glucose ?
54
Vitamin C- Functions
1. Functions as an electron transfer molecule for enzymes involved in
collagen formation and stabilization
2. Antioxidant
3. Involved in catecholamine synthesis
4. Cholesterol metabolism
5. Synthesis: Carnitine, Steroid
6. Uptake of non-heme iron
55
Vitamin C function in Collagen and formation and stabilization
via hydroxylation of proline & lysine which are required to allow the formation of the triple helix and
the cross linking of the collagen chains). (Most well-described function and clinically demonstrated
in the Scurvy which is a disease of impaired collagen synthesi
56
Vitamin C roll in Catecholamine synthesis and what type of vitamin C is involved
tyrosine conversion to the catecholamines
via dopamine β-hydroxylase. Adrenal
(medulla) have much higher concentration
of Vit C
57
Vitamin C involvement in Uptake of non-heme iron
in the gut is facilitated by asobic acid through the
nonenzymatic reduction of Fe 3+ to Fe2+
58
Vitamin C- Deficiency
It may take how many months to develop
Vitamin C is distributed throughout tissues, a deficiency may take several months to exhibit
symptoms.
59
Vitamin C deficiency can result in
Deficiency results in SCURVY
Impaired collagen synthesis
Breakdown of connective tissues
-Gum and tooth
disease
-Bone disease
-Poor wound healing
60
Vitamin C symptoms
- weakness, irritability, pains in joints/muscles
* Bleeding into skin, GI tract & urinary tract
61
Vitamin C plasma value
less then 13 micro meters
62
Vitamin C assays
* HPLC is currently the predominant laboratory method.
* Both serum & leukocyte assays available
63
What vitamin C assay is the best
Leukocyte assay is probably Best
Because of limited stability of ascorbic acid in plasma and serum (better in whole blood).
After only 1 day at room temp, serum ascorbic acid measurements are significantly
diminished and are undetectable by the day 2. Similarly, serum stored at 4 ºC shows
significant decreases in ascorbic acid levels after 3-5 days.
---> serum and plasma measurements do not correlate very well with tissue vitamin C
levels.
64
Vitamin C
what levels vary
* Serum levels vary
- There is an inter laboratory variability with an average CV of 15% across multiple studies. This
variability is most likely related to differences in the differential detection of the many ascorbic
acid isomers/metabolites
65
Vitamin C amount associated with scurvy
less then 0.24 mg/dl associated with scurvy
greater them 0.14 mg/dl will be cleared by the kidneys
66
Vitamin B2
what the name
is what color vitamin
what are activators
Riboflavin
* Yellow-pigmented vitamin
- activators of FMN, FAD +
67
Vitamin B2 functions
– Serves as a cofactor in a variety of oxidative reactions:
Fatty acid oxidation
TCA cycle reactions
Oxidative phosphorylation in the respiratory chain
– Important in metabolism of iron, pyridoxine, and folic acid
– May help protect from oxidants
68
Vitamin B2 Dietary Sources
➢ Found in milk
➢ Organ meats, such as liver
➢ Other meats,
➢ Leafy green vegetables
69
Riboflavin deficiencies result in
Dermatologic changes
Mouth lesions
Glossitis (smooth tongue)
Eyelid spasms & conjunctival congestions
Hematologic dyscrasias
70
Riboflavins better measurement
* Measurement of RBC riboflavins & flavins
- (FMN, FAD) are better than serum
71
Riboflavin and its two cofactor active forms are
Riboflavin and its two cofactor-active forms riboflavin 5’ phosphate mononucleotide (FMN) and
flavin adenine dinucleotide (FAD +) (ßthe most water soluble) exhibit fluorescence.
* FAD + is orange fluorescence;
* Riboflavin & Riboflavin 5’ phsophate fluoresce yellow-gre
72
Riboflavin has what activity in RBCs
* Glutathione reductase activity (coefficient) in RBC (EGRAC)
73
Pyridoxine
Group of compounds are structurally related to
Group of compounds structurally related to pyridoxal phosphate (P5P, PLP)
74
Riboflavin is what number of B vitamin
Vitamin B2
75
Functions of Pyridoxine
- Important co-factors for catalysts in transamination (transferase) and
decarboxylation of amino acids
- Active in > 60 enzyme systems
76
Pyridoxine Dietary sources
-Primarily in meat, poultry, fish
-Also in sweet potatoes
-Other vegetables
77
Best known function of the pyridoxine cofactors are
Best known functions of the pyridoxine cofactors
are their roles in the conversion of tryptophan
to serotonin, tryptophan to nicotinic acid and
metabolites (niacin)
78
Pyridoxine deficiencies
symptoms are
* Weakness
* Abdominal pain, vomiting
* Seizures
79
Pyridoxine: Deficiencies
Conditions associated with deficiencies include
-Alcoholism
-Pregnancy
-Certain drug therapies: Ca ++ channel blockers, oral contraceptives,
isoniazid, steroids, penicillamine
80
Pyridoxine: Deficiencies
Measurements is usually by what
HPLC
81
Niacin ( nicotinic acid)
Function
Coenzyme
The active cofactor forms: collectively called the ‘pyridine nucleotides’
Niacin is a component of the coenzymes NAD+ & NADP+
NAD + & NADP+: involved in oxidation-reduction reactions
Example: glutamate dehydrogenase, LDH & G6PDH
82
Pyridoxine is what B vitamin
vitamin B6
83
Niacin( Nicotinic acids) are involved in what type of reactions
NAD + & NADP+: involved in oxidation-reduction reactions
Example: glutamate dehydrogenase, LDH & G6PDH
84
Niacin (nicotinic acid) Dietary source
-Meats, poultry, fish
-Grains (except corn), esp. whole grains
-Flours, cereals
-Nuts, legumes
-Anything rich in tryptophane is typically a good source of niacin
--NAD + & NADP+ can also be synthesized from liver tryptophane
85
NAD and NADP can also be synthesized from
The liver
86
-Anything rich in tryptophane is typically a good source of
Niacin
87
Niacin Deficiency
causes what condition
Early symption
* Niacin deficiency causes a condition called “pellagra”
* Early symptoms include lethargy, anorexia, weakness, digestive disturbances,
weight loss, dermatitis
88
Niacin - Deficiency
Late symptoms
and Pellagra is characterized by
* Late symptoms include mucus membrane inflammation
à Result in diarrhea, urethritis and vaginitis
à Mental disturbances with disorientation
** Pellagra is sometimes hallmarked by the ‘3 D’s—Diarrhea, Dermatitis, Dementia
89
Niacin Toxicity
* Symptoms of toxicity include:
Cutaneous flushing, gastric irritation, liver dysfunction with jaundice, hyper uricemia,
impaired glucose tolerance
* Niacin is sometimes prescribed in high doses to treat elevated LDL cholesterol
90
Niacin is what number of B vitamin
Vitamin B3
91
Thiamine function and number of B vitamin
B1
* Function:
--As thiamine pyrophosphate, it is a cofactor in enzymatic decarboxylation of
ketoacids in the formation of ketols
--Major carbohydrate pathways
--Metabolism of branched chain amino acid
92
How does Thiamine function in the Carbohydrate pathway
Pyr---> Acetyl CoA
93
Thiamine Dietary sources
--Yeast, wheat, whole grain and enriched breads, cereals
* Highly water soluble & easily leached from foodstuffs during washing or
boiling
94
Thiamine deficiency
symptoms
Alcoholic & Elderly
* anorexia, alcoholism, vomiting & diarrhea, edema, cardiac failure
---> Mg ++ deficiency(alcoholism): impairs thiamine activation
----> Associated with poor appetite, fatigues and peripheral neuritis
95
Thiamine is associated with what type of people
* elderly adults with psychiatric disorders
96
Thiamine deficiency
what type of therapy
(Loop Diuretic –elderly adults take this sometimes)
97
Servere Deficiency of Thiamine presents as a what
neuropathy (beriberi)
-Wet [heart & circulatory system]
-Dry [neuronal damage]
--> loss of muscle strength
---> eventually muscle paralysis
98
Biotin is part of the
Biotin is what sensitive and poorly what
* Biotin is part of the B complex (B7 )
** Biotin is heat sensitive and poorly soluble in water
99
Biotin acts as
* Acts as a coenzyme in pathways of gluconeogenesis, FA synthesis and AA
metabolism
coenzyme for carboxylation & carboxyl group exchange
100
enzymes that rely on Biotin
acetyl CoA, propionyl CoA, pyruvate carboxylase, methyl malonyl
oxaloacetic transcarboxylase (Impt as coenzymes in some of these enzyme rxns/activities)
101
Biotin is inhibited by
Inhibited by raw egg whites in diet (binds to avidin in egg whites)
102
Biotin dietary sources
Found in many foods, especially liver and other organ meats, kidney, milk, egg yolk,
yeast, nuts, legumes
103
Biotin deficiencies
✦ Dermatitis
✦ Neurologic changes, mental changes
✦ Nausea & anorexia
✦ Alopecia: autoimmune skin disease
✦ Impaired immunity
✦ Anemia
✦ Peripheral vasoconstriction
✦ Coronary ischemia
104
Biotin Deficiencies
Autoimmune skin disease that leads to hair loss
Alopecia
105
Pantothenic acid (B3/B5)
Essential what
Involved in what types of metabolism
* Essential growth factor
* Involved in fatty acid metabolism
106
Metabolically, pantothenic acid is converted to what
4-p-pantothenine which is bound to coenzyme A
or another acyl carrier protein. CoA complex functions like ”acyl group transfer
enzyme” (COO- )
107
Pantothenic Acid (B3/B5)
Dietary sources
liver & other organ meats, milk, eggs, fish (especially salmon), peanuts and other
legumes, mushrooms, whole grains
108
Pantothenic Acid (B3/B5)
what is not known
Pantothenic acid deficiency has been induced experimentally and signs of deficiency include
apathy, depression, increased infections, burning sensations, and muscle weak
109
Vitamin B12 and Folate
how do they interact and assayed
Vit B 12 and folate interact
metabolically
à a deficiency in either results
in megaloblastic anemia
110
Vitamin B12 functions
synthesis of
folate
111
Vitamin B12:
name
is what structure
Cobalamin
Vit B 12 is a tetrapyrrol ring structure with a central cobalt atom
112
Vitamin B12: Cobalamin
Functions
1. Important in hematopoiesis
2. Acts as an adenosyl cobalamin (Coenzyme B12),
functions in the formation of CNS myelin sheath
3. Amino acid synthesis
esp. branched-chain ketoacid metabolism
4. Folate synthesis
113
Folate synthesis is required for
Required for synthesis of Purine & Pyrimidine needed for DNA synthesis
114
Vit B 12 : Cobalamin
Dietary sources
how is vitamin B12 absorbed
Vitamin B12 type one one name
--Meat, eggs, milk
--> Vegetarians are at risk for deficiency
* Vit B 12 absorbed in GI tract after complexing with intrinsic factor (IF)
* Vit B 12 transported in serum by transcobalamins I(cobalophilin), II, III.
115
Intrinsic factor comes from
gastric parietal cells
116
Vitamin B12 deficiencies
Result in what symptoms due to what
what types of anemia
* Result in neurologic symptoms due to myelin sheath degeneration
* Megaloblastic anemia due to impaired DNA synthesis, which results from folate
deficiency
117
hereditary VitB12 is known as
Imerslund Syndrome
118
Older adults have higher incidence of Vit B12 deficiency due to
prob. due to poor
nutrition/ absorption
119
Vitamin B12 measurements and Evaluation
Levels measured by immunoassay
* Once deficient confirmed, necessary to determine the cause of Vit B 12
deficiency
à often associated with defects in secretion of intrinsic factor
* Function test: traditional Schilling Test (not performed often
120
Schillings test is for what and steps
Vitamin B12
1.) The Schilling test evaluates absorption of an oral dose of radioactive B-12 by measurement of urinary excretion of the radiolabeled vitamin.
2.) First--A large injection of B-12 is first administered to bind all B-12 binding sites.
3.) Then the oral radioactive dose of B-12 is administered.
If little radiolabeled vitamin is excreted (<10%), this generally indicates either malabsorption or lack of intrinsic factor.
4.) Wait 3-5 days for all radiolabeled B-12 to clear from body.
5.) Repeat test, but include an oral dose of IF (intrinsic factor) with the radioactive B-12.
6.) If the oral dose of IF causes increased absorption and excretion of the radiolabeled, then it is labeled a true pernicious anemia ( lack of IF).
7.) If it is not corrected it is an intestinal malabsorption problem, such as tropical sprue of D. latum infection
121
Folic Acid is also known as
pteroylglutamic acid
122
Folate is necessary for
what is necessary for folate metabolism
-Folate is necessary for normal DNA synthesis
* Vit B 12 is necessary for the metabolism of folate, converting THF to 5’,10’methyl-THF form
required for DNA synthesis
123
Folic Acid - pteroylglutamic acid
Dietary sources
Primarily found in green leafy vegetables
Fruits
Organ meats
Boiling & use of large amounts of water result in vitamin destruction ( or washing away)
124
Folic acid Dietary concerns
American diet may be inadequate in folate needs during adolescence, pregnancy and lactation
Rapid depletion may occur with increased need
Growth in adolescence, poor teen diet may result in deficiency
125
Individuals planning families should wait to have adequate what
Individuals planning families should be sure to have adequate folate for one year prior to pregnancy (some say males, too).
Folate is part of prenatal vitamin supplement
126
Folate Deficiency results in
Characterized chemically-
Hematological Characteristics-
results in megaloblastic anemia due to abnormal DNA synthesis
* Megaloblastic Anemia:
Characterized chemically by low erythrocyte folate and increased
homocysteine levels
Hematological Characteristics: macroovalocytes, hypersegmented
neutrophils, and megaloblastic marrow
127
Classic Vitamin B12 assay
-Competitive Protein Binding Assays.
-The intrinsic factor was used as the binder and Co 57 as the radiolabel
128
Vitamin B12
current assays
competitive binding immunoassay (Ab binder);
some form of FPIA or chemiluminescent IA
Boiling or chemical destruction of endogenous binders is required
129
For Vitamin B12 use what samples and protect from
Fasting samples
* Must use serum: heparin binds Vit B 12
* Protect from light= Vit B 12 is photolytic
130
Recent food intake increases what
Vitamin B12 serum
131
Vitamin B12 storage
4 o C for
24 hours; -20 o C if > 24 hrs
132
For Classic folate assay use
classic was CPB with β-
lactoglobulin as a binder and I125 as radiolabel
133
Current method for Folate
-Current is immunoassay with Ab as binder
(FPIA or MEIA)
**Boiling or use of chemical inhibitors required to destroy
endogenous protein binders
or blocking may be used. (Endogenous binders
are albumin & FBP)
134
Folate assays what samples are used
-Both Serum and RBC hemolysate are used as samples
* Fasting samples
135
Folate Assay
Storage of serum specimens
4o C for 24 hours; -20 o C if > 24 hrs
136
Reference values
Serum folate 1.9—14 ng/ml
RBC folate 200—1000 ng/ml
137
Additional Assays: Vit B12 & Folate
-Serum & urinary methylmalonic acid
Will be increased in Vit B12 deficiency, but normal in folate deficiency
* Homocysteine
Will be increased in both Vit B12 and folate deficiency
138
Carnitine (Bt)
types
L-carnitine & Acylcarnitines
---> ‘conditionally essential’ nutrient (AA)
139
Carnitine (Bt)
Dietary resources
Average diets provide
Strict Vegetarian diets provide
Found in meat, poultry, fish and dairy products
Plants contain little, except peanut butter, asparagus and avocados
Average diets provide > half of human requirement; most is absorbed
“Strict vegetarian diets” provide ~10% of requiremen
140
Carnitine metabolism
requires what for synthesis
where is the synthesis
New synthesis requires N-tri-methyllysine residues of proteins;
--> rate determined by the availability
Synthesis: Liver, Brain, Kidney.
Storage: Muscle
141
Carnitine: Metabolism
Uptake from gut via
Excreted in
Carnitine Transport Protein
urine (free & esterified form)
142
Carnitine Function
Facilitates entry of
Facilitates entry of long-chain FA into mitochondria for energy
production
143
Carnitine: Primary Deficiency
results in
type of genetic disorder
Children symptoms
Rare
* Results in muscle weakness and fatigue
* Usually an “autosomal recessive disorder”
* Children: cardiomyopathy, hypoglycemia, elevated ammonia, muscle
weakness
144
Administration of large doses of carnitine (temporarily) reverses what
primary carnitine deficiency
Administration of large doses of carnitine (temporarily) reverses
the disorder (which is a result of a mutation of the organic cation
transporter “OCNTN2”
145
Other causes of primary carnitine deficiency
without cardiomyopathy are not clearly understood and “do
not always respond to carnitine supplements
146
Carnitine Deficiency, Acquired
* Inadequate intake
* Increased urinary loss
* Pregnancy and breast feeding: éé demand
* Infants, children, and patients on long-term parenteral nutrition
“most vulnerable groups”
147
Secondary deficienciey results in
Patients on “hemodialysis” may lose
Muscle dysfunction
Patients on “hemodialysis” may lose carnitine in dialysis fluid (not yet
recommended supplementation)
148
Carnitine: Other
Carnitine therapies are
are sometimes used with disorders of ammonia
metabolism, liver disorders
149
Valproate is uses to
Valproate [used to treat epilepsy] is associated with liver toxicity: Carnitine
sometimes used in the management of liver injury caused by valproate.
Some studies of Alzheimiers dlsease
150
L-Acetyl- Carnitine
somewhat beneficial in various trials of HIV-associated neuropathy
Some studies show benefits in treatment with carnitine for diabetes nepthropathy
151
Vitamin Supplementation
-Vitamin supplementation may sometimes be warranted in nutritional
deficiencies
* No evidence exists to show intakes in excess of what is needed for
general health is useful
* Megadoses of vitamins have not shown to prevent common cold or
cancer or heart disease
