Metabolism Flashcards
Benign appearance of fructose in blood and urine. Name enzyme deficiency and disease?
Essential Fructosuria
Fructokinase
Symptoms after consuming fruit, juice, honey. Hypoglycemia, jaundice, cirrhosis + vomiting
Fructose Intolerance
Def Aldolase B
-Fructose-1 phosphate accumulates, decreases phosphate available for gluconeogensis + glycogenolysis
Infantile cataracts, possible failure to track objects or to develop a smile. Disease, enzyme, what accumulates
Galactokinase deficiency
Galactitol accumulates - relatively mild
FTT, jaundice, HM, infantile cataracts, intellectual disability, possible E coli sepsis in neonates. Disease, enzyme, treatment
Classic Galactosemia
Absent galactose-1-phosphate uridyltransferase – galactitol accumulates (esp in lens of eye)
Tx: exclude galactose and lactose (glucose + galactose)
Enzyme that converts glucose to sorbitol
Location with primarily this enzyme
Aldose reductase
The lens
Enzyme that converts sorbitol to fructose
Sorbitol dehydrogenase
Dx lactase deficiency
Decrease stool pH
Inc breath Hydrogen content
Hyperammonemia in neonate, poorly regulated respiration and body temp. Poor feeding, dev delay, intellectual disability. Def? Cofactor for what?
N-acetylglutamate synthase deficiency
Required cofactor for CPS-1 (mitochondria, urea cycle)
Elevated orotic acid in blood and urine, dec BUN, syx of hyperammonemia. First few days of life, or can be later. No megaloblastic anemia. Enzyme, inheritance, and ddx
Ornithine transcarbamylase deficiency (most common urea cycle disorder)
X-linked recessive
Body can’t eliminate NH4, converts excess carbamoyl phosphate to orotic acid
Ddx: Orotic Aciduria (pyrimidine synthesis, has megaloblastic anemia)
Intellectual disability, growth retardation, seizures, fair skin, eczema, musty body odor. Enzyme (2), what becomes essential, dx, tx
PKU
Def in phenylalanine hydroxylase OR its cofactor BH4 (tetrahydrobiopterin)
Tyrosine becomes essential
Dx w/ clinical picture + excess phenylalanine leads to increase phenylketones in urine (phenylacetate, phenyllacetate, phenylpyruvate)
Tx: avoid phenylalanine (in aspartame), increase tyrosine + BH4 supplementation
Severe CNS defects, intellectual disability, and death. Urine with maply syrup/burnt sugar smell. Enzyme + dx + tx
Maple Syrup Urine Disease
Dec alpha-ketoacid dehydrogenase (B1) – cant break down branched amino acids (Isoleucine, Leucine, Valine)
Inc alpha-ketoacids in blood (esp leucine)
Tx: restrict these AA in diet, give thiamine
Dark connective tissue, brown pigmented sclera, urine turns black w/ prolonged air exposure to air. Name, enzyme, pathway, possible complication
Alkaptonuria (Ohchronosis)
Homogentisate Oxidase (degrades tyrosine to fumarate)
Accumulate homogentisic acid in tissues (pigment forming)
Can have debilitating arthralgias - homogentisic acid toxic to cartilage
Ethanol Metabolism
______ to ______ to ______
2 enzymes
Ethanol → Acetylaldehyde → Acetate
- Alcohol Dehydrogenase (cytosol)
- Acetylaldehyde Dehydrogense (mito)
Fomepizole MOA, Use
Blocks alcohol dehydrogenase
Use w/ ethelyene glycocol or methanol poisoning
Disulfram MOA, Use
Blocks acetylaldehyde dehydrogenase (accumulate acetylaldehyde)
To discourage alcoholics from relapsing
Ethanol metabolism kinetics?
Zero-order (constant amount per unit time)
Limiting reagant for EtOH metabolism?
NAD+
Ethanol metabolism effects on other pathways (3)
- pyruvate → lactate (lactic acidosis)
- oxaloacetate → malate (can’t do gluconeogenesis → fasting hypoglycemia)
- dihydroxyacetone → glycerol-3-phosphate (combines w/ fatty acids and makes TGs – fatty liver, hepatosteatosis)
Chronic EtOH disfavors what type of metabolism, and favors what?
High NADPH/NAD+ ratio disfavors TCA (and production of NADPH)
-favors use of acetyl-CoA for ketogenesis + lipogenesis
Function of Pyruvate Dehydrogenase Complex? What stimulates it?
Mitochondrial enzymes complex, links glycolysis + TCA Stimulated by exercise 1. Inc NAD+/NADH ratio 2. inc ADP 3. inc Ca2+
Required Enzymes and cofactors for PD complex?
TLC for No Body
- thiamine (B1) + pyrophosphate
- Lipoic acid
- CoA (B5 - pantothenic acid)
- NAD+ (niacin, B3)
- FAD+ (riboflavin, B2)
Formula of PD complex
Pyruvate + NAD+ + CoA → acetyl-CoA + CO2 + NADH
What other complex requires TLC for No Body?
alpha-ketoglutarate dehydrogenase
- converts alpha ketoglutarate to succinyl-CoA (TCA cycle)
MOA of arsenic? Clinical presentation
Arsenic inhibits lipic acid
s/s: vomiting, rice water stools + garlic breath
Neuro defects, lactic acidosis, increased serum alanine in infancy? Disease, mechanism, tx
Pyruvate Dehydrogenase Deficiency
Build up of pyruvate, shunted to lactate (LDH) and alanine (ALT)
Tx: inc ketogenic nutrients (high fat + onLy pureLy ketogenic amino acids → Lysine + Leucine)
4 fates of pyruvate
- alanine (via ALT + B6): amino acids from muscle to liver
- acetyl-CoA (via pyruvate dehydrogenase w/ TLC,NB): glycolysis to TCA
- oxaloacetate (via pyruvate carboxylase w/ Biotin): can replenish TCA or be used in gluconeogenesis
- lactic acid (via lactic acid dehydrogenase w/ B3) - end of anaerobic glycolysis (+ Cori Cycle)
What does the urea cycle do?
converts excess nitrogen (NH3) from amino acid catabolism to urea → excretion by kidneys
What other pathways are affected by hyperammoniunemia?
excess NH4+ depletes alpha-ketoglutarate
inhibits TCA cycle
4 ways to treat hyperammonemia
- Dec protein in diet
- Lactulose: acidifies GI tract, traps NH4+
- Rifaximin: dec NH4+ making bacteria in gut
- Benzoate or Phenylbutyrate: bind amino acids and increase excretion
When to screen for PKU and why
2-3 days after birth, bc will be normal first few days due to mom’s enzymes
Maternal PKU findings in infant
microcephaly, intellectual delay, congenital heart defects, and growth retardation
Intellectual disability, osteoporosis, marfanoid habitus and inc homocysteine in urine
Homocystinuria
Complications of homocystinuria
osteoporosis kyphosis marfanoid habitus down and in lens subluxation thrombosis atherosclerosis
3 causes of homocysteinuria
- cystathione synthase deficiency
- decreased affinity of cystathione synthase for cofactor (B6- pryidoxal phosphate)
- homocysteine methyltransferase def (aka methionine synthase)
Tx Cystathionine Def
- Dec methionine
- Inc Cysteine and B12 and folate in diet
* *push pathway away from deficienct enzyme
Tx affinity problem w/ cystathione + B6
Lots of B6 and cysteine in diet
Tx methionine synthase def (and other name for enzyme)
methionine synthase aka homocysteine methyltransferase
tx: inc methionine in diet
What’s defective in cystinuria?
What occurs?
defective amino acid transporter in distal PCT and intestine
Excess cystine in urine → preciptates urinary cystine stones (hexagonal)
amino acids missing in cystinuria
COLA - can't reabsorb Cysteine Ornithine Lysine Arginine
How to dx cystinuria
urinary cyanide-nitroprusside test
what is cystine?
2 cysteines connected w/ di-sulfide bond
How to tx cystinuria (big picture and 2 ways)
Dec solubility of stones, good hydration
- alkinize urine (potassium CITRATE or Acetazolamide)
- Chelating agents (penicillamine)
hypochromic megaloblastic anemia, neuro syx, growth retardation, high levels of orotic acid in urine
Orotic Aciduria
Cause of orotic aciduria?
problem with pyrimidine synthesis
1. orotate phosphoribosyl transferase and OMP decarboxylase
Tx oritic aciduria
Uridine supplementation
-converted to UMP and inhibits CPS-II
