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Culture Documents
Vitamins A, D, E, K
Absorption dependent on ileum and
pancreas
Accumulate in body fat, more potential for
toxicity
Fat malabsorption conditions may cause
deficiency
Cystic fibrosis, celiac sprue, mineral oil intake
Vitamin A (Retinol)
Found: liver, leafy vegetables
Functions: antioxidant, constituent of retinal
visual pigment
Deficiency: night blindness, dry skin
Excess: head ache, arthralgias, fatigue, skin
changes, sore throat, alopecia
Teratogenic: cleft palate, cardiac problems
Remember bear hunter who eats liver!
Vitamin D
Found: Fortified milk
Function: Increases intestinal absorption of
Vitamin D, continued
D2
Found in plants, pharmacological form
D3
Found in milk, formed in sun exposed skin
25-OH D3
Storage form
1,25-(OH)2D3 (Calcitriol)
Active form
Vitamin E
Found: Vegetable oils, nuts, leafy
vegetables
Function: Antioxidant, protects RBCs and
membranes from free radical damage
Deficiency: Increased fragility of RBCs,
muscle weakness, neurodysfunction
Vitamin K
Found: Leafy vegetables, some fruits
Function: Necessary for synthesis of
Vitamin B1 (thiamine)
Function: Component of thiamine
Beriberi (dry)
Polyneuritis, symmetrical muscle wasting
Beriberi (wet)
High-output cardiac failure (dilated cardiomyopathy)
edema
Vitamin B2 (riboflavin)
Function: Cofactor in oxidation and
Vitamin B3 (niacin)
Function: Constituent of NAD, NADP, used in
absorption)
Malignant carcinoid syndrome (increased
tryptophan metabolism
INH (anti-TB) (decreased B6)
Vitamin B5 (pantothenate)
Function: Component of CoA (cofactor in
Vitamin B6 (pyridoxine)
Function: Converted to pyridoxal,
Folic Acid
Function: Converted to tetrahydrofolate
methotrexate
Biotin
Function: Cofactor for carboxylation
Minerals, 98
Zinc
Function: Involved in activity of 100+
Malnutrition, 98
Kwashiorkor
Protein deficiency
Skin lesions, liver malfunction (fatty change),
edema, anemia
Malnutrition, 98
Marasmus
Total calorie deficiency
Tissue and muscle wasting, loss of
Ethanol Metabolism, 98
NAD+, NADP+
Require Vitamin B3 (niacin) for production
NAD+
Catabolic processes, carry reducing equivalents
as NADH
NADP+
Anabolic processes, supply reducing equivalents
as NADPH
NADPH also used in respiratory burst, P-450
FAD+
Requires Vitamin B2 (riboflavin) for production
Metabolism, 101
reactions
Aerobic metabolism
Produces 32 (heart/liver) 30 (muscle) ATP per
glucose
Anaerobic metabolism
Produces 2 ATP per glucose
Glucokinase
Liver and pancreas -cells, low affinity (high Km)
Pyruvate dehydrogenase
Deficiency, 103
Back up of substrate (pyruvate, alanine),
leads to lactic acidosis
Congenital and acquired (B1 deficiency)
forms
Neurologic deficits
Treat by increasing intake of ketogenic
nutrients (high fat, lysine, leucine)
Glucose-6-Phosphate
Dehydrogenase Deficiency, 106
G6PD produces NADPH, necessary to
keep glutathione reduced, which detoxifies
free radicals/peroxides
Decreased NADPH leads to hemolytic
anemia due to damage from oxidizing
agents
X-linked recessive,
most common
enzyme deficiency
Glucose-6-Phosphate
Dehydrogenase Deficiency, 106
Oxidizing agents include fava beans,
sulfanamides, primaquine, anti-TB drugs
Affected individuals have malarial
resistance
Heinz bodies
Bite Cells
From phagocytic removal of Heinz bodies by
spleen
Glucose-6-Phoshate
Dehydrogenase Deficiency, 106
Disorders of Fructose
Metabolism, 106
Fructose intolerance
Hereditary deficiency of aldolase B
Autosomal recessive
Fructose-1-phosphate accumulates, leading to
Disorders of Fructose
Metabolism, 106
Essential fructosuria
Defect in fructokinase
Autosomal recessive
Benign, asymptomatic
Disorders of Galactose
Metabolism, 107
Classic galactosemia
Absence of galactose-1-phosphate
uridyltransferase.
Autosomal recessive
Toxic damage from galactitol
Failure to
thrive, jaundice,
hepatomegaly, infantile
cataracts, mental retardation
Exclude galactose and lactose
from diet
Disorders of Galactose
Metabolism, 107
Galactokinase deficiency
Autosomal recessive
Galactitol accumulates if galactose is present in
diet
Galactose appears in blood
and urine, infantile cataracts,
failure to track objects, lack of
social smile
Hyperammonemia, 108
Acquired (liver disease) or hereditary
(urea enzyme deficiencies)
Results in excess NH4+, depletes ketoglutarate, inhibits TCA cycle
Tremor, slurring speech, somnolence,
vomiting, cerebral edema, blurred vision
Treat with benzoate, phenylbutyrate
Ornithine Transcarbamoylase
Defiency, 108
Most common urea cycle disorder
X-linked recessive
Interferes with elimination of ammonia
May present in first days of life
Excess carbamoyl phosphate converted
to orotic acid
Orotic acid in blood and urine,
decreased BUN, hyperammonemia
Phenylketonuria, 109
Decreased phenylalanine hydroxylase
or tetrahydrobiopterin cofactor.
Tyrosine can not be synthesized,
becomes essential
Autosomal recessive
Increased phenylalanine
leads to excess
phenylketones in urine.
Phenylketonuria, 109
Mental retardation, growth retardation,
seizures, fair skin, eczema, musty body
odor
Treat by increased tyrosine and
decreased phenylalanine in diet
Maternal PKU, (deficiency in pregnancy)
causes mental retardation, growth
retardation, microcephaly, heart defects
Alkaptonuria, 109
Congenital deficiency of homogentisic acid
oxidase in degradative pathway of tyrosine
Autosomal recessive
Dark connective tissue, pigmented sclera,
urine turns black on standing, arthralgias
Albinism, 109
Albinism, 109
Can result from lack of migration of
neural crest cells.
Increased risk of skin cancer
Homocystinuria, 100
Autosomal recessive
3 forms, all result in excess homocysteine
1. Cystathionine synthase deficiency
2. Decreased affinity of
cystathionine synthase for
pyridoxal phosphate (treat
with increased B6 in diet)
3. Homocysteine
methyltransferase deficiency
Homocystinuria, 110
Cystine becomes essential
Increased homocysteine in urine, mental
retardation, osteoporosis, tall stature,
kyphosis, lens subluxation,
atherosclerosis (MI and stroke)
Cystinuria, 110
Hereditary defect of renal tubular amino
acid transporter for cysteine, ornithine,
lysine, arginine in proximal convoluted
tubule.
Excess cystine in precipitates, forms
cystine kidney stones.
Autosomal recessive
Treat with acetazolamide to
alkalinize urine.
Adenosine Deaminase
Deficiency, 111
Excess ATP and dATP imbalances
nucleotide pool (feedback inhibition of
ribonucleotide reductase)
Prevents DNA synthesis
Decreased lymphocyte count
Major cause of severe combined
immunodeficiency disorder
Lesch-Nyhan Syndrome,
111
Absence of HGPRT leads to defective
purine salvage pathway
Excess uric acid production
X-linked recessive
Autosomal recessive
Increased orotic acid in urine,
megaloblastic anemia, failure to thrive
Treat with oral uridine
Insulin, 112
Synthesized in pancreas cells
Released in response to ATP from
glucose metabolism (depolarizing K+
channels)
Anabolic effects:
Insulin, 112
Inhibits glucagon release by pancreas
cells
Insulin dephosphorylates
Serum C-peptide only present with
endogenous protein
insulin use
Insulin, 112
Insulin moves glucose into cells
Some cells do not need insulin, use a
glucose transporter
skeletal muscle
Glycogen, 112
Branches: (1,6) bonds
Linkages: (1,4) bonds
Glycogen phosphorylates
Skeletal muscle
Hepatocytes
Glycogen is stored and undergoes
Findings
Deficient enzyme
Severe fasting
hypoglycemia,
increased glycogen in
liver, increased blood
lactate, hepatomegaly
Glucose-6-phosphate
Pompes (II)
Cardiomegaly
Lysosomal -1,4
glucosidase (acid
maltase)
Coris (III)
Debranching enzyme
McArdles (V)
Exercise
1st (seconds) Stored ATP, creatine
Pancreatic lipase
Degradation of dietary lipase in small
intestine
Lipoprotein lipase
Degradation of TG in chylomicrons and
VLDL
Hepatic TG lipase
Degradation of TG in IDL
Chylomicron
Delivers dietary TGs to tissue
Delivers cholesterol to liver as chylomicron
Lipoprotein, 118
VLDL
Delivers hepatic TGs to tissue
Secreted by liver
B-100, C-II, E
Hypertriglyceridemia
Increased VLDL
Elevated TG
Hepatic overproduction of VLDL
IDL
Formed by degradation of VLDL
Delivers TGs and cholesterol to liver, degraded to LDLs
B-100, E
LDL
Delivers hepatic cholesterol to tissues
Formed by lipoprotein lipase modification of
VLDL in tissue
Taken up by target cells via receptor-mediated
endocytosis
B-100
Familial dyslipidemia IIa
Increased LDL
Elevated cholesterol
Autosomal dominant, absent/decreased LDL
receptor
HDL
Mediates reverse cholesterol transport from
tissues to liver.
Repository of apoC and apoE
Secreted from liver and intestine
Abetalipoproteinemia, 118
Hereditary inability to synthesize
lipoproteins, because of deficiency in
apoB-100 and apoB-48
Autosomal recessive, appears early in life
Failure to thrive,
steatorrhea,
acanthocytosis, ataxia,
night blindness