Flashcards in Metabolism 90-96 Deck (27):
1
Oxidative step of HMP shunt
Irreversible
G6P--G6P dehydrogenase--> ribulose 5 Phosphate
Rate limiting!!
2
G6P dehydrogenase defiency
X linked recessive -MOST COMMON HUMAN ENZYME DEFICIENCY
NADPH keeps glutathione reduced
Leads to hemolytic anemia when stressed
(Ex: fava beans, sulfonamides, primaquine, antiTB drugs, INFECTION)
Peripheral smear: Heinz bodies (denatured Hg) and Bite cells (removal of Heinz bodies by splenic macrophages)
3
Essential Fructosuria
Defect in fructokinase
Benign, asymptomatic condition.
Fructose in blood and urine
4
Fructose intolerance
Defect in aldolase B
Autosomal recessive
Fructose 1 phosphate accumulates --> decreased phosphate
INHIBITS GLYCOGENOLYSIS AND GLUONEOGENESIS
Urine dipstick negative (tests for glucose only)
Tx: decrease intake of fructose and sucrose
5
Galactokinase deficiency
Hereditary deficiency of galactokinase
Galactitol accumulates
S/s when INFANT BEGINS FEEDING
Galactosemia, galactosuria and infantile cataracts
Failure to tracks objects or develop a social smile
6
Classic galactosemia
Absence of galactose 1 phosphate uridyltransferase--phosphate depletion
Autosomal recessive
Accumulation of galactitol behind the lens of the eye
Failure to thrive, jaundice, hepatomegaly, infantile cataracts, intellectual disability
E. COLI SEPSIS IN NEONATES
To: exclude galactose and lactose
7
Lactase deficiency primary, secondary and congenital
Primary: age dependent decline after childhood (black, Indians and Asians)
Secondary: loss of brush border due to gastroenteritis, autoimmune disease
Congenital: rare, due to defective gene
8
Essential amino Acids
PVT TIM HaLL
Phenylalanine
Valine
Threonine
Tryptophan
Isoleucine
Methionine
Histidine
Leucine
Lysine
9
Basic Amino Acids
Histidine, lysine and arginine
Are and Lys are increased in histones
10
HMP shunt
Source of NADPH (necessary for reductive reactions)
Yields ribose
NO ATP used or produced
Two phases occur in the cytoplasm
1. Oxidative: irreversible
2. Non-Oxidative: reversible
Sites - liver, adrenal ctx, RBC's
11
Urea cycle components of urea
NH3, CO2
Aspartate donates NH2
12
Rate limiting enzyme of urea cycle
CPS I
Activated by N-acetylglutamate
13
Ornithine transcarbamylase deficiency
X linked recessive
Orotic acid in blood and urine
Decreased BUN
NO megaloblastic anemia vs orotic aciduria
HYPERAMMONEMIA
TX: low protein diet, biotin
14
Ammonia transport in the blood
Amino acid is transferred onto glutamate, which then transfers ammonia onto Pyruvate, forming alanine
Alanine transfers ammonia to the liver, where it undergoes the urea cycle
15
HYPERAMMONEMIA
S/s tremor, vomiting, slurring of speech, somnolence, cerebral edema, blurring of vision
Acquired (liver disease)
Hereditary (due to ornithine transcarbamylase deficiency or Nacetylglutamate synthase deficiency)
--result is excess NH3, which depletes alpha ketoglutarate, interrupting the TCA cycle
Tx: limit protein in diet
Lactulose
Rifaximin
Benzoate, phenyl acetate, phenylbutyrate
16
N acetyl glutamate synthase deficiency
Cofactor for carbamoyl phosphate synthetase I
HYPERAMMONEMIA
NEONATES: poor feeding, developmental delay
(Same presentation as CPS I deficiency)
17
AA precursor nitric oxide, urea and creatinine
Arginine
18
AA precursor heme
Glycine --(B6)-->porphyrin --> heme
19
AA precursor for GABA and glutathione
Glutamate --(B6)-->GABA
Glutamate -->glutathione
20
Tryptophan derivatives
-(B2, B6)-->Niacin-->NAD/NADP
--(BH4, B6)-->serotonin -->melatonin
21
Phenylalanine derivatives
--(BH4)-->tyrosine--(BH4)->Dopa --(B6)-->dopamine --(vitC)->NE--(SAM)->EPI
22
Phenylketonuria
Decreased phenylalanine hydroxylase (or decreased BH4 cofactor)
Tyrosine becomes essential
S/s seizures, fair skin, eczema MUSTY BODY ODOR
Increased phenylalanine
Autosomal recessive
23
Maternal PKU
Lack of proper dietary therapy during pregnancy
S/s microcephaly, intellectual disability, growth retardation, congenital heart defects
24
Maple syrup urine disease
Blocked degredation of branched amino acids (leucine, isoleucine and valine) "I Love Vermont maple syrup"
Causes increased alpha ketoacids in the blood (esp. Leucine)
S/s SEVERE CNS defects, intellectual disability, death
Tx; restriction of branched AA's in diet, thiamine supplementation
25
Alkaptonuria
Congenital deficiency of homogenisate oxidase (degradation of tyrosine to maleylacetoacetic acid)
Homogentisic acid accumulates in tissue
Autosomal recessive
Bluish-black connective tissue and sclerae
Urine turns black on prolonged exposure to air
Debilitating arthralgias
26
Homocyteinuria
Excess homocysteine due to:
1. Cystathionine synthase deficiency
--decreased methionine, INCREASED CYSTEINE, B12 and folate in diet
2. Decreased affinity of cystathionine synthase for PLP
--Tx: increased B6 and cysteine in diet
3. Methionine synthase deficiency
--Tx: increased methionine in diet
S/S intellectual disability, Marranos habits, DOWN AND INWARD LENS SUBLUXATION (vs. Marfans-upward)
27