Metabolism 90-96

Question 1

Oxidative step of HMP shunt

Answer 1

Irreversible
G6P–G6P dehydrogenase–> ribulose 5 Phosphate
Rate limiting!!

Question 2

G6P dehydrogenase defiency

Answer 2

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)

Question 3

Essential Fructosuria

Answer 3

Defect in fructokinase
Benign, asymptomatic condition.
Fructose in blood and urine

Question 4

Fructose intolerance

Answer 4

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

Question 5

Galactokinase deficiency

Answer 5

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

Question 6

Classic galactosemia

Answer 6

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

Question 7

Lactase deficiency primary, secondary and congenital

Answer 7

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

Question 8

Essential amino Acids

Answer 8

PVT TIM HaLL
Phenylalanine 
Valine
Threonine
Tryptophan 
Isoleucine
Methionine
Histidine
Leucine
Lysine

Question 9

Basic Amino Acids

Answer 9

Histidine, lysine and arginine

Are and Lys are increased in histones

Question 10

HMP shunt

Answer 10

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

Question 11

Urea cycle components of urea

Answer 11

NH3, CO2

Aspartate donates NH2

Question 12

Rate limiting enzyme of urea cycle

Answer 12

CPS I

Activated by N-acetylglutamate

Question 13

Ornithine transcarbamylase deficiency

Answer 13

X linked recessive 
Orotic acid in blood and urine 
Decreased BUN
NO megaloblastic anemia vs orotic aciduria
HYPERAMMONEMIA
TX: low protein diet, biotin

Question 14

Ammonia transport in the blood

Answer 14

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

Question 15

HYPERAMMONEMIA

Answer 15

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

Question 16

N acetyl glutamate synthase deficiency

Answer 16

Cofactor for carbamoyl phosphate synthetase I
HYPERAMMONEMIA
NEONATES: poor feeding, developmental delay
(Same presentation as CPS I deficiency)

Question 17

AA precursor nitric oxide, urea and creatinine

Answer 17

Arginine

Question 18

AA precursor heme

Answer 18

Glycine –(B6)–>porphyrin –> heme

Question 19

AA precursor for GABA and glutathione

Answer 19

Glutamate –(B6)–>GABA

Glutamate –>glutathione

Question 20

Tryptophan derivatives

Answer 20

• (B2, B6)–>Niacin–>NAD/NADP

- -(BH4, B6)–>serotonin –>melatonin

Question 21

Phenylalanine derivatives

Answer 21

–(BH4)–>tyrosine–(BH4)->Dopa –(B6)–>dopamine –(vitC)->NE–(SAM)->EPI

Question 22

Phenylketonuria

Answer 22

Decreased phenylalanine hydroxylase (or decreased BH4 cofactor)
Tyrosine becomes essential
S/s seizures, fair skin, eczema MUSTY BODY ODOR
Increased phenylalanine
Autosomal recessive

Question 23

Maternal PKU

Answer 23

Lack of proper dietary therapy during pregnancy

S/s microcephaly, intellectual disability, growth retardation, congenital heart defects

Question 24

Maple syrup urine disease

Answer 24

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

Question 25

Alkaptonuria

Answer 25

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

Question 26

Homocyteinuria

Answer 26

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)

Question 27

Cystinuria

Answer 27

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)