Metabolism 90-96 Flashcards Preview

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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

Cystinuria

Auto recessive
Defect of renal PCT and intestinal aa transporter: prevents absorption of cystine, ornithine, lysine, arginine (COLA)
Excess cysteine--> recurrent hexagonal cysteine stones
Tx: urinary alkalinization (acetazolamide) and chelating agents (penicillamine)