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Flashcards in Metabolism Deck (40):

rate limiting enzyme of glycolysis

-- inhibited by ATP, citrate
-- stimulated by AMP and fruc-2,6-BP


rate limiting enzyme of gluconeogenesis

--stimulate by ATP, AcetylCoA
-- inhibited by AMP, fruc-2,6-BP


rate limiting enzyme of TCA cycle

isocitrate dehydrogenase
- stimulated by ADP
- inhibited by ATP, NADH


rate limiting enzyme of glycogenesis

glycogen synthase
+ G6P, insulin, cortisol
- epi, glucagon


rate limiting enzyme of glycogenolysis

glycogen phosphorylase
+ epi, glucagon, AMP
- G6P, insulin, ATP


rate limiting enzyme of HMP shunt



rate limiting enzyme of cholesterol synthesis

HMG-CoA reductase
+ insulin, thyroxine
- glucagon, cholesterol


electron transport inhibitors

rotenone, cyanide, antimycin A, CO
-- directly inhibit electron transport, causing a decreased proton gradient and block of ATP synthesis


ATP synthase inhibitors

-- directly inhibits mitochondrial ATP synthase, causing increased H+ gradient. No ATP is produced because electron transport stops


uncoupling agents

2,4-dinitrophenol, aspirin, thermogenin in brown fat
-- increase permeability of mito membrane, causing decreased H+ gradient and increased O2 consumption. electron transport continues without ATP synthesis, produces heat.


Von Gierke Disease (type I)

glycogen storage disease with severe fasting hypoglycemia, increased glycogen in liver, increased blood lactate and hepatomegaly
-- G6Phosphatase deficient
-- treat with frequent oral glucose/cornstarch, avoid fructose and galactose


Pompe Disease (type II)

glycogen storage disease with cardiomyopathy and systemic findings leading to early death
-- lysosomal alpha 1,4 glucosidase (acid maltase) deficient
-- Pompe trashes the Pump (heart liver muscle)


Cori disease (type III)

milder form of type I (Von Gierke) glycogen storage disease with normal blood lactate levels
-- debranching enzyme (1,6 glucosidase) deficient
-- gluconeogenesis is inact


McArdle disease (Type V)

glycogen storage disease with increased glycogen in muscle, but cannot break it down, leading to painful muscle cramps, myoglobinuria after exercise, and arrthythmias 2/2 electrolyte abnormalities
-- skeletal muscle glycogen phosphorylase deficiency
-- McArdle = Muscle


Fabry disease

-- alpha galactosidase A deficiency
-- ceramide trihexoside builds up
-- X linked inheritance
-- peripheral neuropathy, angiokeratomas, CV/renal disease


Gaucher disease

-- most common lysosomal storage disease
-- glucocerebrosidase deficiency --> glucocerebroside buildup
-- hepatosplenomegaly, pancytopenia, aseptic necrosis of the femur, bone crises, Gaucher cells (lipid laden resembling crumpled tissue paper)
-- treat with recombinant enzyme


Neimann-Pick Disease

-- sphingomyelinase deficiency leads to buildup of sphingomyelin
-- progressive neurodegeneration, HSmegaly, cherry red spots on macula, foam cells (lipid-laden macrophages)
-- "No man picks his nose with his sphinger (sphingomyelinase)"


Tay-Sachs Disease

-- hexosaminidase A deficiency --> buildup of GM2 ganglioside
-- progressive neurodegeneration, developmental delay, "cherry-red" spots on macula, lysosomes with onion skin, no HSmegaly
--Tay SaX (heXosamindase)


Krabbe disease

-- galactocerebrosidase deficiency --> buildup of galactocerebroside and psychosine
-- peripheral neuropathy, developmental delay, optic atrophy, globoid cells


Metachromatic leukodystrophy

-- arylsulfatase A deficiency --> buildup of cerebroside sulfate
-- central and peripheral demyelination with ataxia, dementia


Hurler Syndrome

-- alpha-L-iduronidase deficiency leading to heparan sulfate and dermatan sulfate buildup
- Dont give Hurler Harry a cookie - developmental delay, gargoylism, Hurler, HSmegaly, airway obstruction, corneal clouding


Hunter syndrome

-- XR iduronate sulfase deficiency leading to heparan sulfate and dermatan sulfate buildup
-- milder Hurler syndrome +aggressive behavior and NO corneal clouding
-- Hunters see clearly (no corneal clouding) and aim for the X (X-linked recessive)



inhibits lipoic acid, a cofactor needed for pyruvate dehydrogenase complex
-- leads to vomiting, rice-water stools and garlic breath


G6PD deficiency

decreased NADPH in RBCs leads to hemolytic anemia after oxidative stress because NADPH cannot keep glutathione reduced, which in turn cannot detoxify free radicals
-- more common in blacks
-- Heinz bodies and bite cells seen


essential fructosuria

benign condition due to defect in fructokinase
-- fructose appears in the blood and urine


fructose intolerance

hereditary deficiency in aldolase B leads to F-1P to build up, which results in inhibition of glycogenolysis and gluconeogenesis
-- hypoglycemia, jaundice, cirrhosis and vomiting following consumption of fruit, juice or honey
-- reducing sugar found in urine
-- treat with decreased fructose and sucrose


galactokinase deficiency

hereditary deficiency leads to buildup of galactitol
-- relatively mild condition with galactose in blood and urine
-- infantile cataracts, lack of tracking, dont develop social smile


classic galactosemia

absence of galactose-1-phosphate uridyltransferase leads to buildup of galactitol
-- failure to thrive, jaundice, hepatomegaly, infantile cataracts, intellectual disability
-- exclude galactose and lactose from diet


ornithine transcarbamylase deficiency

most common urea cycle disorder
-- X-linked recessive
-- excess carbamoyl phosphate is converted to orotic acid
-- findings: increased orotic acid in blood and urine, decreased BUN, symptoms of hyperammonemia, no megaloblastic anemia



due to decreased phenylalanine hydroxylase or decreased tetrahydrobiopterin cofactor
-- tyrosine becomes essential, phenylketones found in urine
-- intellectual disability, growth retardation, seizures, fair skin, eczema, musty body odor
-- treat with decease phenylalanine and increased tyrosine in diet



congenital deficiency of homogentisate oxidase in the degradative pathway of tyrosine to fumarate
-- AR benign disease with dark connective tissue, brown pigmented sclera with urine that turns black when exposed to air
-- can have disabling arthralgias



3 forms, all resulting in excess homocysteine
-- increased homocysteine in urine, intellectual disability, osteoporosis, tall stature, kyphosis, downward lens subluxation, thrombosis and atherosclerosis



hereditary defect of renal and intestinal AA transporter for cystine, ornithine, lysine, and arginine (COLA)
-- excess cystine in the urine can lead to hexagonal cystine stones
-- urinary cyanide-nitroprusside test is diagnostic
-- treat with urinary alkalinization and good hydration


maple syrup urine disease

-- blocked degradation of branched AA (isoleucine, leucine and valine)
-- increased alpha ketoacids in the blood, esp those of leucine
-- severe CNS defects, intellectual disability and death
-- treat with restriction of ILV in diet, and thiamine supplementation


5 cofactors required for alpha-ketoacid dehydrogenase, pyruvate dehydrogenase, and alpha-ketoglutarate dehyrogenase

Tender Loving Care For Nancy
- thiamine pyrophosphate
-coenzyme A


type I hyperchylomicronemia

increased chylomicrons, TG and cholesterol
-- AR lipoprotein lipase deficiency or altered apolipoprotein C-11
- causes pancreatitis, HSmegaly, and eruptive/pruritic xanthomas (no increased atherosclerosis)


type IIa familial hypercholesterolemia

- increased LDL, cholesterol
- AD, absent or defective LDL receptors
- hetero - 330mg/dL, homo - 700+
- accelerated atherosclerosis, tendon xanthomas, and corneal arcus


type IV hypertriglyceridemia

- elevated VLDL, TG
- AD, hepatic overproduction of VLDL
- causes pancreatitis


orotic aciduria

inability to convert orotic acid to UMP in pyrimidine sythesis
- presents with megaloblastic anemia resistant to folate and B12, growth retardation and neuro abnormalities
- no hyperammonemia signs like ornithine transcarbamylase deficiency (urea cycle d/o)
- supplement with uridine


propionic acidemia

- propionyl CoA caboxylase deficiency that leads to the buildup of propionic acid in the breakdown of branched chain amino acids (valine, isoleucine, threonine, methionine)
- presents with poor feeding, lethargy, hypotonia, dehydration and anion gap acidosis during the first few days of life