2nd half of biochem path

Question 1

Pyruvate dehydrogenase complex deficiency

Answer 1

(requires B1, B2, B3, lipoic acid and B5)

Causes a build-up of pyruvate that gets shunted to lactate (LDH) and alanine (ALT)

Neurological defects, lactic acidosis, high serum alanine

Tx: intake of ketogenic nutrients in favor of glucogenic: i.e. high fat content and high lysine and leucine

Question 2

Rotenone poisoning

Answer 2

Inhibits Complex I of OxPhos

Question 3

Antimycin

Answer 3

Inhibits Complex III of OxPhos

Question 4

Cyanide

Answer 4

Inhibits Complex IV of OxPhos

Question 5

CO

Answer 5

Inhibits Complex IV of OxPhos

Question 6

Oligomycin

Answer 6

Inhibits Complex V of OxPhos (ATP synthase)

Question 7

Glucose-6-phosphate dehydrogenase deficiency

Answer 7

NADPH is needed to keep glutathione reduced (protects against oxidative damange esp. in RBCs, such agents include sulfonamides, primaquine, INH)

XL-R African populations (malarial resistance)
Heinz bodies and bite cells

Question 8

Essential fructosuria

Answer 8

AR defect in fructokinase
Benign, no trapping in cells
Fructose in blood and urine

Question 9

Fructose intolerance

Answer 9

AR defect in aldolase B (F1P accumulates in cells, trapping P thus inhibiting glycogenolysis and gluconeogenesis)

Symptoms post honey, fruit, juice, no glucosuria
Hypoglycemia, jaundice, cirrhosis, vomiting

Tx: decreased intake of fructose and sucrose

Question 10

Galactokinase deficiency

Answer 10

AR; galacticol accumulates if galactose in diet (mild)

Sy: galactosemia, galactosuria, infantile cataracts (no tracking or smile)

Question 11

Classic galactosemia

Answer 11

AR deficiency in gal-1-P uridyltransferase
Accumulation of galacticol in lens)
Sy: begin with infant feeding (lactose in milk); FtT, jaundice, hepatomegaly, infantile catarcts, intellectual disability, E. coli (lactose fermenter)

Tx: remove galactose and lactose

Question 12

Sorbitol can also mediate peripheral neuropathy

Answer 12

Can mediate peripheral neuropathy, cataracts and retinopathy b/c in DM patients, glucose converted to sorbitol by aldose reductase. this is because these tissues lack Sorbitol dehydrogenase present elsewhere

Question 13

Hyperammonemia

Answer 13

Can be caused by deficiency of urea cycle enzymes:
E.g.: arginase, argininosuccinase, argininosuccinate synthetase, ornithine transcarbamylase I

Result: excess ammonia, inhibits TCA cycle

Tx: limit protein, lactulose, rifamixin, benzoate, phenylacetate, phenylbutyrate

Causes: tremor, slurred speech, somnolence, vomiting, cerebral edema, burred vision

Question 14

Ornithine transcarbamylase deficiency

Answer 14

XLR, most common urea cycle d/o (others are AR)
First days of life, carbamoyl phosphate sunged to pyrimidine synthesis so elevated orotic acid
low BUN despite symptoms of hyperammonemia

Question 15

Phenylephrine derivatives

Answer 15

Tyrosine Thyroxine
Dopa Melanin
Dopamine
NE
Epi

Question 16

Tryptophan derivatives

Answer 16

Niacin NAD+ NADP+

Serotonin Melatonin

Question 17

Histidine

Answer 17

Histamine

Question 18

Glycine

Answer 18

porphyrin heme

Question 19

Glutamate

Answer 19

GABA and Glutathione

Question 20

Arginiene

Answer 20

Cr Urea NO

Question 21

Phenylketoneuria (PKU)

Answer 21

AR defect in phenylalanine hydroxylase or low tetrahydrobiopterin
Y becomes essential, high F and phenylketonuria

Intellectual disability, growth retardation, seizures, fair skin, eczema, musty odor

Tx: reduce F intake, give Y and BH4
Avoid aspartame; screen newborns

Question 22

Maple syrup urine disease

Answer 22

AR blocked degradation of branching AAs (isoleucine, leucine and valine) due to less alpha-ketoacid dehydrogenase

leucine in blood

Severe CNS defects, intellectual disability and death

Tx: no I,L,V supplement thiamine

Question 23

Alkaptonuria

Answer 23

Homigentisate oxiadase deficiency in degredation of Y to fumarate

AR: pigment

Blue/black CT, cartilage, sclera, arthralgias

Question 24

Homocysteinuria

Answer 24

Causes (AR):

Cystathionine sythase def. (restrict methionine; giv cysteine, B6/9/12)

Low B6 or cysteine

Metionine synthase def. (give methionine)

All cause: homocysteinuria, osteoporosis, marfanoid, downward lens subluxation, CV thrombi, kyphosis, intellectual disability

Question 25

Cystinuria

Answer 25

Defect in PCT transport of cystine, ornithine, lysine and arginine (COLA)
Hexagonal xtals
Tx: alk urine (Kcitrate, acetozolamide)
AR

Question 26

Systemic 1˚ carnitine deficiency

Answer 26

toxic accumulation of LCFAs

Weakness, hypotonia, hypoketoic hypoglycemia

Question 27

MCAD

Answer 27

can’t break down FAs to Acetyl-CoA
Acyl-carnitines in blood with hypoketoic hypoglycemia

Vomiting, lethargy, seizure, coma, liver dz

Avoid fasting