Biochem Flashcards
Chronic Granulomatous dz = deficiency in
Nicotinamide Adnein Dinucleotide phosphate oxidase
Child with Cardiomyopathy, glossitis, hypotonia, elevated creatine kinase. Low Leukocyte and maltase levels. Exercise intolerance
Pompe dz
Absent alpha-1,4-glucosidase (cant hydrolyze glycogen, AKA acid maltase)
Glycogen accumulates
Child with bad eye sight, tall, awkward gait, scoliosis
Homocystinuria
Defect in cystathionine synthase (homocystein -> cystationine)
Marfan features + sublaxation of the lensCan have atherosclerosis
ar
I-cell dz
Failure to phosphorylate mannose-6-P residues = exocytosis of lysosomal enzymes
Deficient in N-acetylglucosamine
Child with FTT, vomitting associated with milk, jaundice, bilateral clouding of eye lenses, hepatomegaly, developmental delay
Galactosemia, ar
Galactose-1-P uridyltranserferase deficiency
Avoid galactose and milk (lactose)
Galactokinase deficiency causes less severe symptoms
Dz such as syphilis target a specific intracellular antigen in their host
Cardiolipin. Phospholipid in the inner mitochondrial membrane.
Virilized female neonate with hypotension and hyperkalemia
21-hydroxylase deficiency
Virilized female neonate with hypertension and hypervolemia
11beta-hydroxylase deficiency
Female teenager that does not undergo normal sexual maturation during puberty. Excessive aldosterone causes hypertension and hypokalemia
17alpha-hydroxylase deficiency
Unable to convert progesterone and pregnenolone to cortisol, test, and estrogen
Severe fasting hypoglycemia, high blood lactate, hepatomegaly. Usually presents around 6 mo when feedings are spread out
Von Gierke dz
Glucose 6 P deficiency
Tx - frequent oral glucose. Avoid fructose and galactose
childhood with hepatomegaly, hypoglycemia, weakness, hypotonia. Milder form of von Gierke with short outer chains
Cori dz Debranching enzyme (alpha-1,6-glucosidase) deficiency Gluconeogenesis is intact
Exercise intolerance, painful cramps, myoglobinuria
McArdle dz
Defecient in muscle glycogen phosphorylase (myophosphorylase)
Tx - Vit B6
Peripheral neuropathy of hands/feet (burning parathesia, temperature intolerance), angiokeratomas (red papules on abdomen, scrotum, decreased sweating), cardio/renal dz
Fabry dz
alpha galactosidase A deficiency
Ceramid trihexoside accumulation
X linked
Hepatosplenomegaly, osteoporosis, bone crisis, lipid-laden macrophages
Gaucher dz
Glucocerebrosidase defeciency (beta-glucosidase)
Glucocerebroside accumulates
Tx - recombinant glucocerebrosidase
Progressive neurodegeneration, hepatosplenomegaly, foam cells, cherry-red spot on macula
Niemann-Pick dz
Sphingomyelinase deficiency
Sphingomyelin accumulation
Neurodegeneration, developmental delay, cherry-red spot on macula
Tay-Sachs dz
Hexosaminidase A deficiency
GM2 ganglioside accumulates
Peripheral neuropathy, developmental delay, optic atrophy, globoid cells
Krabbe dz
Galactocerebrosidase deficiency
Galactocerebroside and psychosince accumulate
Central and peripheral demyelination, ataxia, and dementia
Metachromatic leukodystrophy
Arylsulfatase A deficiency
Cerebroside sulfate accumulates
Developmental delay, gargoylism, airway obstruction, corneal clouding, hepatosplenomegaly
Hurler syndrome
alpha-L-iduronidase deficiency
Heparan sulfate, dermatan sulfate accumulates
Mild hurler syndrome plus aggressive behavior. NO corneal clouding
Hunter syndrome
Iduronate sulfatase deficiency
Heparan sulfate, dermatan sulfate accumulate
XR
Urine turns dark over time, black cartilage. Brownish gray deposits in sclerae, ears. Arthralgia, nephrolithiasis in severe cases
Alkaptonuria
Deficiency in homogentisic acid oxidase
Defect in tyrosine degredation
Endocrine hormones using cAMP pathway
FLAT ChAMP
FSH, LH, ACTH, TSH CRH, hCG, ADH (V2), MSH, PHT calcintonin, GHRH, glucagon
Endocrine hormones using cGMP pathway
BAD GramPa (vasodilators) BNP, ANP, EDRF (NO)
Endocrine hormones using IP3 pathway
GOAT HAG
GnRH, Oxytocin, ADH (V1), TRH, Histamine (H1), Angiotensin II, Gastrin
Endocrine hormones using Intracellular receptor pathway
PET CAT on TV
Progesterone, Estrogen, Testosterone, Cortisol, Aldosterone, T3/T4, Vit D
Endocrine hormones using Receptor tyrosine kinase pathway
Insuline, IFG1, FGF, PDGF, EGF (growth factors)
Endocrine hormones using nonreceptor tyrosine kinase pathway
PIGGlET (JAK/STAT pathway)
Prolactin, Immunomodulators, GH, G-CSF, Erythropoietin, Throbopoietin
Infant with FTT, seizures, sweet smelling urine
Maple Syrup Urine dz
Defect in alpha-keto acid dehydrogenase
Restrict branched chain amino acids: Isoleucine, Leucine, Valine
Building block of fatty acid synthesis
Malonyl CoA
Patient with bright red vessels and the smell of bitter almonds on their breath
Cyanide poisoning
inhibits cellular respiration, ETC
Tx with nitrate and sulfate
Vitamin deficiency in alcoholism
Thiamine
High serum lactate and low pH (lactic acidosis)
Teenage girl with amenorrhea and a recently enlarged clitoris. Elevated testosterone:DHT
5alpha-reductase deficiency
Male internal genitalia, ambiguous external genetalia
Elevated testosterone and LH with low DHT
Function of Vitamin K
Carboxylation of glutamic acid residues
Asymptomatic patient with incidental finding of fructosuria
Essential fructosuria
Deficiency in Fructokinase
Fructose - F1P
Patient with jaundice, hepatomegaly, vomiting, lethargy, convulsions, and hypoglycemia following fructose ingestion
Hereditary fructose intolerance Deficiency in Aldolase B F1P -> dihydroxyacetone-P Can lead to renal/liver failure Avoid fructose and sucrose
Non essential amino acids
Aspartic acid, glutamic acid, arginine
Patient with oval shaped slightly depigmented nevus and angiofibroma with intellectual disability. MRI with multiple nodules of glial proliferation.
Tubersous Sclerosis
AD, tuberin and hamartin proteins
Chr 9 and 16
Strong association iwth tumors and typical ashy leaf spot on skin.
Baby with microcephaly, limb dislocations and fistulas of the heart associated with inhibition of cell migration
Fetal alcohol syndrome
Kid with n/v, encephalopathy, jaundice following a infection and OTC aspirin use
Reye syndrome
transiently impaired metabolism of fatty acids by hepatic mitochondria
Inheritance pattern of VHL
AD
Chr 3
Lack of menarche, breast tissue and female external genitalia but vagina ends in a blind pouch
Androgen insensitivity
Cafe au lait spots, neurofibromas, lisch nodules (pigmented iris hamartomas). Skeletal defects (scoliosis, vertebral defects)
Neurofibromatosis type 1
AD, chr 17
Fluoroquinolones target
DNA gyrase
Michaelis-Menten constant increases and maximum reaction rate does not change
Competitive inhibitor
Constant Michaelis-Menten constant and decreased max reaction rate
Non competitive inhibitor
Regulator of the RLS in glycolysis
Citrate
RLS is F6P -> F16BP by phosphofructokinase
Bilateral acoustic neuromas
Neurofibromatosis type 2
AD, chr 22
skeletal abnormalities, restricted joint movement, coarse facial features, psychomotor impairment. Death in first decade
I cell dz (mucolipidosis II)
Lysosomal enzymes are usually translated and N-glycosylated in RER and the trafficked to Golgi. In Golgi, N-acetlyglucosamine-1P transferase Phosphorylates Mannose 6P to target to lysosome. Exocytosis in deficiency
Digoxin toxicity is made worse by
Hypokalemia
Recurrent infections and negative nitroblue tetrazolium dye reduction test.
Chronic granulomatous Dz
Deficiency in nicotinamide adenine dinucleotide phosphate oxidase
Retardation, short stature, hypotonia, hyperphagia, obesity, small hands/feet, hypogonadism
Prader-Willi
Deletion of Paternal chr 15
Lysosomal proteins are tagged by Mannose 6 P in which organelle?
Golgi
This isn’t done properly in I cell dz and results in exocytosis of lysosomal proteins
Physical and mental retardation, megalocytic anemia, elevated urinary orotic acid levels, FTT, hyperammonemic encephalopathy in first weeks of like
Hereditary orotic aciduria
Defect in uridine 5’ mono phosphate
Tx - uridine supplementation
Pathophysiology of ehlers-danlos
Deficiency in procollagen peptidase - cleaves terminal pro peptides from pro collagen in extra cellular space. Impairment causes soluble collagen that doesn’t cross link.
Also defect in lysl hydroxylase crosslinking
Normally RAS proteins are only active when bound to?
GTP
Initial step in gluconeogenesis after 12-18 hours of starvation
Pyruvate -> oxaloacetate -> phosphoenolpyruvate by pyruvate carboxylase
Severe fatigue, splenomegaly, early satiety/discomfort, hepatomegaly, anemia, bone marrow fibrosis
Primary myelogibrosis
Megakaryocytic hyperplasia -> marrow replacement by collagen deposition
Jak2 mutation
why give amyl nitrite in cyanide poisoning?
cyanide inhibits cytochrome c Oxidase in the ETC. inhaled amyl nitrite oxidizes ferrous iron (fe2+) to ferric (fe3+) in hemoglobin transforming it to methemoglobin. methemoglobin cannot bind oxygen, but has high affinity for cyanide sequestering it away from the mitochondria
pericolicular hemorrhages, myslgia, subperiostial hematoma, gingivitis
scurvy
give ascorbic acid
function of the zinc finger motif
dna binding domain found in many transcription factors. intracellular receptors for steroids, thyroid hormones, and vit DEKA act as transcription factors and contain zinc fingers
what causes the hemorrhage and necrosis of mamillary bodies in thiamine deficiency?
impaired glucose utilization in CNS due to decreased pyruvate DH, alpha ketogluterate DH, and erythrocyte transketolase activity.
marcanoid habitus, poor vision, and thombolic occlusions is? and treat with?
homocystinuria
supplement with pyridoxine (b6) and restrict methionine
epinepherine is made in the adrenal medulla by
phenylethanolamine-N-methyltransferase. this enzyme is activated by cortisol
monomeric subunits of hemoglobin are stucturally analogous to
myoglobin
symmetrical peripheral neuropathy in distal limbs with sensory and motor impairment
dry beri beri (b1)
symmetrical peripheral neuropathy with sensory and motor involvement plus cardiac involvement
wet beri beri (b1)
healthy kid fasting for 1day with vomiting, lethargy. and extreme weakness. low glucose, no acetoacetate, high AST/ALT
hypoketotic hypoglycemia due to defect in beta oxidation
usually due to a defect in acyl-CoA DH
cannot free FAs of ketone bodies
tx by avoiding fasting
which hormone can maintain blood glucose levels duing starvation by binding an intracellular receptor?
cortisol
stimulates release of heat shock proteins and increases transcription of enzymes required for gluconeogenesis
Dx of Fabry dz increases risk of what during adulthood?
cerebrovascular events
cardiac dz
renal failure due to Gb3 buildup in glomerulous and DCT
pt with erythrocytosis due to a lys to met substitution in residue 82 in beta hemoglobin
familial erythrocytosis
reduces hemoglobin binding with 2,3-bisphosphoglycerate causing increased oxygen affinity in hemoglobin.
during replication, which polymerase replaces RNA primers with DNA?
DNA Pol I
DNA pol III = elongation
tetrahydrobiopterin (bh4) is a cofactor for the synthesis of?
serotonin, tyrosine, and DOPA (NE, DA, and epi) precursor.
form of PKU
in the TCA cycle, GTP is synthesized during?
succinyl-CoA to succinate by succinyl coa synthetase. GTP is now a available to be used by PEP carboxylase to convert OAA to PEP during fasting
sickle cell is due to which mutation?
glutamic acid to valine at residue 6 in beta globin
what are the steps in base excision repair?
glycosylases recognize abnormal base and vleaves the base
endonuclease cleaves 5’ site
lyase completes extraction of the remaining sugar phosphate group
dna polymerase fills the gap
ligase seals the nick
cytosine is deaminated into
uracil
adenine is deaminated into
hypoxanthine
guanine is deaminated to
xanthine
previously well nourished patients have hepatic reserves of which vitamin that can last for several years despite dietary deprivation
cobalamin (b12)
all other water soluble vitamins are quickly depleted
which sequela will develop if there is a left shift on the hemoglobin dissociation curve
low tissue oxygen content will trigger erythrocytosis in response to increased epo
in nitrite poisoning what happens to the partial pressure of arterial oxygen?
it will be unchanged but there will be a dusky change in the skin color due to methemoglobinemia and there will be functional anemia
pt with recurrent blistering on the back of the hands and forearms that heal with hyperpigmentation after rupturing.
porphyria cutanea tarda
deficient in uroporphyrinogen decarboxylase
this is a late derangement causing photosensitivity due go a cumulation of porphyrinogens
assoc with alcohol use, smoking, hep c, hiv
orogressive neurologic deterioration and elevated prolactin in a PKU patient that has been supplemented with tyrosine
deficiency of dihydrobiopterin reductase which is a cofacgor in phe to tyrosine
g6pd is the RLS in pentose phosphate pathway. when this enzyme is absent, what other pathway is inhibited?
cholesterol, fatty acid, and steroid synthesis
NAPDH from PPP is required for anabolic reactions
in a reperfusion injury (or acute compartment syndrome) which enzyme is most likely to neutralize these toxic molecules
superoxide dismutase
but also glutathione peroxidase and catalase
In ligands (ie phenylepherine) bind a G protein receptor, what is activated?
Phospholipase C -> synthesizes IP3 and DAG
DAG -> activates Protein Kinase C
IP3 -> increases intracellular calcium with activates Protein kinase C
In HbS, the glutamic acid -> valine change has what effect on the hemoglobin?
This leads to an alteration in the beta globin surface that interacts with a complimentary site on another Hb and the normal hydrophobic interaction is disrupted between hemoglobin molecules.
Same pathology is seen in HbC
A pt has dark brown soft gallstones composed of calcium bilirubinate with variable amounts of cholesterol. What enzyme contributed to the pathogenesis?
Pigment stones - calcium salts and unconjugated bilirubin
Usually secondary to E. coli or helminth infection in biliary tract causing increased beta-glucoronidase activity
Can also be seen in chronic hemolytic anemia
neonate with hypotonia and vomiting and elevated urine methylmalonic acid and propionic acid
organic acidemia, ar
defect in methylmalonyl-CoA causing metabolic acidosis and hypoglycemia, hypertketonemia, amd hyperammonemia
pathophhs in a typical fat fertile forty pt
cholesterol stones
when more cholesterol than bike salts, cholesterol precipitates out
cholesterol 7 alpha hydroxylase synthesizes bike acid salts - when inhibited (fibrates) more cholesterol precipitates
pt with xanthomas, premature atherosclerosis and accumulation of chylomicrons and VLDL remnants
familial dysbetalipoproteinemia
defective apoE
pt with acute pancreatitis lipemia retinalis, xanthomas, and accumulates chylomicrons
familial chylomicronemia syndrome
defect in lipoprotein lipase, apoC-2
pt with premature atherosclerosis, tendon xanthomas, xanthelasmas with elevated LDL
familial hypercholesterolemia
defect in LDL receptor, apoB-100
pt with coronary disease, pancreatitis, and dm with elevated VLDL
familial hypertriglyceridemia
polygenic protein defect
fair skinned kid, blue eyes, musty body odor
PKU
defect in tyrosine synthesis causes low melanin
high levels of fructose2,6BP inhibits? activates?
alanine to glucose (glucogenesis) is inhibited
activates PFK1 to facilitate glucolysis (f6p to f16bp)
what is the end product of sorbitol metabolism in the lens of a healthy individual?
fructose
sorbitol is formed by aldolase reductase
defect in DM leads to cataracts
scurvy causes hypoactivity of an enzyme in which organelle?
RER
alpha chains of collagen are synthesized in the RER and retained there for bydroxylation of proline and lysine by their respective hydroxylases. vitamin c is a required cofactor for both reactions. deficiency leads to impaired triple helix stability and formation of covalent crosslinks
kid with abdominal mass that demonstrates highly developed SER on bx. this tissue likely responds to which endocrine?
ACTH and other endocrines that stimulate steroid and phospholipid biosynthesis. pt likely has an adrenal mass (acth stimulates gluccorticoids, mineralcorticoids, and androgens)
in a patient with DKA, there is increased activity of?
glycerol kinase
phosphorylates glycerol from adipose tissue to g3p. it will be further converted to DHAP which can enter glycolysis or gluconeogenesis
secondary structure of proteins is dependent on?
hydrogen bonds (alpha helix vs beta sheet)
primary structure of proteins is dependent on?
covalent linkage between amino acids
tertiary structure of proteins is dependent on?
ionic bonding, hydrophobic interactions, hydrogen bonds, and disulfide bonds
in a person with folic acid deficiency, supplementation with shat will reduce wrythroid precursor cell apoptosis?
thymidine
thymidylate aynthetase can produce dihysrofolate
this is the de novo pathway of dTMP
thymidine supplementation will also activate the salvage pathway
pt with anemia, dysphagia, and disfigured nails (spoon nails, koilonychia)
iron deficiency anemia
dysphagia is due to esophageal webs (plummer-vinson)
microcytic, hypochromic
supplement with iron and vit c can be added to improve andorption
which step of mrna processing only occurs in the cytoplasm?
interaction with p bodies
these are involved in mrna regulation, storage, and turnover
hnrna modification and splicing of introns occurs in the nucleus
heme synthesis occurs where in erythrocytes?
mitochondria and cytoplasm of erythrocytes
mitochondria are required for the first and final steps
only occurs in erythrocyte precursors that still have a nucleus and mitochondria
in rna processing what sequences do snrps recognize?
5’ splice site - GU
3’ splice site - AG
between HbA, HbS, and HbC which is the least negative? most negative?
least HbC = glutamate to lysine (positive)
most HbA = glutamate (negative)
HbS is a glutamine to valine (neutral)
symptoms of HbC?
asymptomatic and often mild hemolytic andmia and splenomegaly
sometimes RBCs do not produce ATP why?
RBCs can skip a ATP producing step by using bisphosphoglycerate mutase. they do this to create 2,3BP in times of hypoxemia to increase heme affinity for oxygen
a pt with intellectual disability dies from a seizure. autopsy shows pallor of substantia nigra, locus ceruleus, vagal nucleus dorsalis. condition?
PKU
phenylalanine hydroxylase deficiency
Thyroid hormone increases?
glycogenolysis, gluconeogenesis, and lipolysis
Amiodarone is used to treat supreventricular arrhythmia. How does it work?
Longer effective refractory period due to blocking of voltage-gated channels
Class III antiarrhytmic- sotalol, ibutilide, bretylium
A hypercapnic COPD patient will accumulate which enzyme in their lungs?
Carbonic anhydrase
Target of anti-smith Abs?
SLE marker
targets snRNP/snRNA complexes in the nucleus
a Hb with a decreased P50 will have what characteristic?
Higher oxygen affinity
Decreased O2 unloading in the tissues will lead to erythrocytosis
In the fed state, which metabolite will inhibit beta oxidation of fatty acids?
Malonyl-CoA ( made by acetyl-CoA carboxylase in the cytoplasm, RLS in fatty acid synthesis)
Where does beta oxidation of fatty acids occur?
Mitochondrial matrix. The matrix is impermeable to fatty acids and requires carnitine to shuttle the metabolites in. Malonyl-CoA inhibits carnitine acyltransferase
A pt with acidosis will have stimulation of renal ammoniagenesis. Why?
Renal tubular cells metabolize glutamine to glutamate, generate ammonium that is excreted in the urine and bicarb absorbed into the blood.
A baby with a deficiency in tetrahydrobiopterin is hypotonic and has intellectual disability because?
Deficiency in serotonin, tyrosine, DOPA (NE, epi precursor)
Serotonin is made from?
Tryptophan
What molecule is responsible for increasing the rate of reaction during skeletal muscle contraction?
Calcium
Activates Phosphorylase kinase which regulates glycogen phosphorylase in glycogen break down
A pt has multiple xanthomas, family history of cardiac dz, lipid laden macrophages, and lacks ApoE3/ApoE4
Familial dysbetalipoproteinemia
Impaired chylomicron remnant uptake by liver cells
What molecule increases following activation of Phospholipase c?
Calcium
DAG -> PKC -> increases intracellular Ca
In collagen, every 3rd residue is?
Glycine
A pt with acute mesenteric ischemia presents with lactic acidosis due to decreased activity of which enzyme?
Pyruvate dehydrogenase
Inhibited by accumulation of NADH so pyruvate is converted to lactate.
Alkaptonuria is due to a defect in?
homogetisic acid dioxygenase
Defect in tyrosine to fumarate
“ochronosis”
Under no physiologic stressors, what can be synthesized by the somatic cells of a healthy adult?
Glutamic acid (transamination of alpha-ketoglutarate)
Disulfiram reactions are caused by accumulation of?
Acethaldehyde
albinism is caused by?
mutation in tryosinase. Impaired conversion of tyrosine to melanin
I hepatocytes how does insulin increase glycogen synthesis?
Protein phosphatase
Insulin binds a transmembrane protein -> tyrosine kinase becomes activated -> phosporylates Insulin receptor substrate 1 (IRS1) -> activates phosphatidylinositol-3-kinase (PI3K) activates protein phosphatase -> dephosphorylates glycogen synthase making the enzyme active to initiate glycogen synthesis
As a bruise turns from dark blue to green, which enzyme is active?
Heme oxygenase degrades heme into biliverdin, CO, and ferric iron
Biliverdin = green
What enzyme turns a bruise from green to yellow?
Biliverden reductase
Biliverden (green) -> bilirubin (yellow)
What is the function of dopamine hydroxylase?
DA -> NE
deficiency = ptosis, orthostatic hypotensioin, hypoglycemia, hypothermia
Following nitrate exposure, which arterial blood value will remain normal?
Partial pressure of oxygen in the arterial blood (represents the amount of oxygen disolved in the plasma
Methemoglobin won’t be albe to bind oxygen causing a functional anemia
toddler with fever, vomiting, sleepiness. Increased blood ammonia, increase urine orotic acid
Ornithine transcarbamylase deficiency
Urea cycle disorder
The excess in carbamoyl phosphate stimulates pyrimidine synthesis leading to an increase in urinary orortic acid
n/v and coma are induced by the hyperammonemic state
Tachypnea due to cerebral edema secondary to the ammonia buildup (respiratory alkalosis)
Southwestern blots detect what type of substance?
DNA - binding proteins such as transcription factors, nucleases, and histones
(c-Jun, c-Fos are nuclear transcription factors that bind DNA via a leucine zipper m
What is the function of transketolase?
Pentose phosphate pathway enzyme. Found in the cytosol. Uses thiamine as a cofactor
What is the function of ornithine transcarbamylase?
Catalyzes the addition of ornithine to cavamoyl phosphate to form citrulline in the urea cycle. Occurs in mitochondria
A new born presents with lethargy, vomiting, hypotonia. Labs demonstrate metabolic acidosis with a large anion gap, ketosis, hypoglycemia. Elevated propionic acid in the plasma and urine. Which amino acids are contributing to this?
Catabolism of isl, val, met, and threonine (IVMT), odd numbered fatty acids, and cholesterol side chains form propionic acid. This is normall converted to methylmalonic acid -> methylmalonyl CoA -> succinyl CoA which enters the TCA cycle
Likely deficient in propionyl CoA carboxylase (propionic acid -> methylmalonyl CoA) causing accumulation of propionic acid
2 y/o presents with neurological syx, hepatosplenomegaly, and a cherry-red macula. PCP expects the child will not survive past 3 years. What is the function of the enzyme that is deficient in this pt?
Converts sphinomyelin to ceramide
Neimann Pick dz
Hepatosplenomgaly, progressive neurodegeneration, Cherry-red spot on macula
Accumulation of sphingomyelin and cholesterol in parenchymal and reticuloendothelial cells.
Lipid laden Macrophages
How do you differentiate between Neimann Pick and Tay Sachs?
Tay Sachs will NOT have hepatosplenomegaly
Both have a cherry red macula
Which tissues will be affected in a pt with osteogenesis imperfecta?
Type I Collagen
Bone, tendons, skin, eyes, ears, teeth
Spontaneous bone fx, slow wound healing, blue sclerae, hearing impairment, joint laxity
Marfanoid habitus with upward displaced lens. CV complication?
Aortic regurgitation due to dilation of aortic root, aortic dissection, MVP
Marfan’s, Mutation in fibrillin gene on chr 15
Essential for elastin in aorta, suspensory ligaments of the eye, and other connective tissues
Acetyle CoA is an allosteric activator of a mitochondrial enzy that catalyzes an irreversible step in gluconeogenesis. What is the product of the reaction?
Oxaloacetate
pyruvate -> oxaloacetate-> PEP
Pyruvate carboxylase is activated by acetyl-CoA and requires biotin and ATP
When desmopressin binds the V2 receptor, what is the result?
Stimulation of adenylyl cyclase (Gs)
desmopressin = ADH analog
Immigrant child presents with anemia and low pyruvate kinase acitivity on his RBC’s. Why does he have splenomegaly?
Red pulp hyperplasia
deficiency causes hemolytic anemia due to lack of ATP to maintain RBC structure. The red pulp of the spleen is involved in removal of damaged RBC’s.
During gluconeogenesis phosphoenolpyruvate carboxykinase uses GTO to synthesize phosphoenolpyruvate to Oxaloacetate. Where does the GTP come from?
GTP is synthesized by succinyl-CoA synthetase during conversion of succinyl-CoA to succinate in the citric acid cycle
During periods of extended fasting, which enzymes are responsible for maintaining glucose levels as well as positive for urine ketones?
Hormone sensitive lipase
Found in adipose tissue and drives the break down of triglycerides into free fatty acids and glycerol to provide substrates for hepatic gluconeogenesis and ketone body formation.
Activated in response to catecholamines, glucagon, ACTH but inhibited by insulin
What rxn does Glucose 6P dehydrogenase catalyze?
glucose-6-Phosphate to 6-Phosphogluconate
What is the goal of the HMP shunt?
Generate lots of NADPH so that glutathione reductase can maintain glutathione in a reduced state. Glutatione protects RBCs from oxidative stress (source of the problem in G6PD deficiency)
As hemoglobin loads oxygen, what molecule is released?
Protons
Haldane effect = as oxygen binds to hemoglobin H+ and CO2 are released from hemoglobin
Bohr effect = High levels of H+ and CO2 facilitate oxygen offloading in the periphery
8 y/o presents with developmental delay, FTT, and episodic seizures. Labs; elevated lactate. What should be supplemented in his diet that won’t exacerbate his lactate levels?
Lysine
Pt has pyruvate dehydrogenase complex deficiency causing lactic acidosis and neurological defects. Cannot convert pyruvate to acetyl-CoA causing shunting to lactic acid. Metabolism of ketogenic aa’s (lysien, leucin) provide energy in the form of acetyl-coA without increasing lactate
Which enzyme has 5’ to 3’ exonuclease ability?
DNA Pol I
Removes RNA primers in the lagging strand
A pt with lead poisoning has similarity to what other disease?
Inherited defect of the heme synthesis pathway can cause acute intermittent porphyria (abdominal pain, skin sensitivity to light, neuropathy)
“Inherited deficiencies in this enzyme lead to photosensitivity and peripheral neuropathy”
A 6 y/o boy presents with a stagger and frequent falls, abnormally high arch of the feet, and dysrhythmia. Uncle had similar symptoms at 12 y/o. Dx and molecular mechanism?
Friedreich ataxia - trinucleotide repeat (GAA)
Unstable repeats impede gene transcription
Decreased production of fataxin at the transcription stage.
High arch = pes cavus
Which enzyme is the rate-determining enzyme in renal gluconeogenesis?
Fructose-1,6-bisphosphatase
Which substrate is used by NADPH oxidase to produce reactive products?
Oxygen
Phagocytes use NADPH oxidase to convert Oxygen to reactive oxygen species (ie Superoxide)
A pt with cirrhosis secondary to HCV presents with encephalopathy. Which substance would be elevated in his astrocytes?
Glutamine
ammonia crosses the BBB and excess glutamine will accumulate within astrocytes. This decreases the availability for conversion to glutamate in the neurons -> disruption of excitatory neurotransmission -> tremors
3 year old with an unremarkable perinatal course presents with bilateral leg stiffness and involuntary movements, cognitive and motor developmental delay. FHx is negative. PE - bilateral spastic paresis of the lower extremities. Labs - elevated arginine in plasma and CSF. The deficient enzyme normally produces?
Urea
Dx = arginase deficiency
Arginase produces urea and ornithine from arginine.
Deficiency = progressive spastic diplegia, growth delay, and abn movements
Tx - arg free, low-protein diet
Unlike other urea cycle disorder - mild or no hyperammonemia
3 year old with cognitive and motor delay dies and at autopsy has pallor of substantia nigra, locus ceruleus, and vagal nucleus dorsalis. Deficiency of which enzyme?
Phenylalanine hydroxylase or tetrahydrobiopterin (cofactor)
PKU
64 y/o male presents with: Bicarb - 12 pH - 7.2 PaCO2 - 26 Lactic acid - 3x normal CT = distal ileal wall thickening and lack of enhancement with IV contrast. Decreased activity of which enzyme?
Pyruvate dehydrogenase
Dx = acute mesenteric ischemia
In hypoxia pyruvate is converted to lactate dehydrogenase
In aerobic conditions pyruvate is converted to acetyl coenzyme A by Pyruvate dehydrogenase
18 y/o male presents with progressive skin rash x 1 yr. Burning sensation over palms and soles exacerbated by stress. Sweats mimimally. PE - clusters of non-blanching red papules in the gluteal, inguinal, and umbilical areas. Labs - no alpha-galactosidase A. Dx and likely to develop?
Fabry disease
Likely to develop renal failure
X-linked, defiency in alpha-galactosidease A and accumulates sphingolipid globotriaosylceramide.
Syx = neuropathic pain and angiokeratomas in youth. Adulthood see glomerular, cardiac, and CV complications
3 year old presents with fatigue and difficulty walking due to fatigue. Mild heart murmur. Glucose - 37 Creatin kinase - 304 Urine protein + Muscle bx - very low carnitine She has a deficiency in synthesizing?
Acetoacetate
Carnitine deficiency impairs fatty acid transport from cytoplasm to mitochondria preventing Beta-ox of fatty acids into acethyl CoA. Leads to cardiac and skeletal myocyte injury (lack ATP from TCA cycle). Impaired ketone production by the liver during fasting
Carbamoyl phosphate synthetase I (CPS I)
Location, pathway, source of nitrogen?
Mitochondria
Urea cycle
Ammonia
Carbamoyl phosphate synthetase II (CPS II)
Location, pathway, source of nitrogen?
Cytosol
Pyrimidine synthesis
Glutamine
Describe pyrimidine synthesis
Carbamoyl phosphate -> orotic acid by CPS II
Orotic acid + PRPP -> UDP
UDP can become dUDP (and eventually dTMP, this requires tetrahydrafolate) or CTP
Describe orotic aciduria
ar
defeciency in UMP synthase
can’t convert orotic acid to UMP leads to elevated orotic acid in the urine, no hyperammonemia
(hyperammonia is in OTC deficiency), megaloblastic anemia (not responsive to B12 supplement)
Supplement with dietary uridine
Describe purine synthesis
PRPP -> IMP (inhibited by 6-mercapto
IMP can be converted in GMP and AMP
Which amino acids can be used as building blocks in purine and pyrimidine synthesis?
Glycine
Aspartate
Glutamine
(And also tetrahydrafolate)
Gout is associated with overactivity in which pathway?
Purine salvage pathway
HGPRT enzyme is very important in the purine salvage pathway. Deficiency leads to?
Lesch-Nyhan syndrome
Overproduce uric acid. Presents with syx of: gout, intellectual disability, self-mutilation (lip biting), aggressive behavior, chorea
Tx - allopurinol
What is adenosine deaminase deficiency?
Defect in Purine salvage pathway
SCID
Deficiency in B and T cells, severe recrruent infections, FTT, no thymic shadow on CXR
RLS enzyme in purine synthesis
glutamine PRPP aminotransferase
RLS enzyme in pyrimidine synthesis
CPS II
Which residues make histone + charged?
Lysine, arginine
Key findings in Ornithine Transcarbamylase (OTC) defieciency
Orotic acid in urine + hyperammonia
IF ammonia level is WNL = Orotic aciduria (this will also have megaloblastic anemia)
Pt with a defect in PRPP synthetase will develop?
Gout
Which hormone can maintain blood glucose levels during prolonged fasting by binding an intracellular receptor?
Cortisol - binds an intracellular receptor and translocates to the nucleus and binds hormone responsive DNA elements - alternate gene expression to augment hepatic glucose production and limit peripheral glucose utilization. Maintains glucose homeostasis
Glucagon binds a transmembrane receptor and epi is a major back up hormone
When Gq is activated what will be activated?
Phospholipase C -> hydrolyzes PIP to form DAG and IP3
IP3 activates PKC -> increases intracellular Ca2+
In the glycolysis pathway which substrate will have the fastest rate of metabolism
Fructose - 1 - Phosphate
In the liver Fructose -> F1P and is rapidly metabolized because it bypasses PFK1 (the RLS of glycolysis)
Glucose, mannose, galactose enter glycolysis prior to PRK-1 and are subjected to the RLS
If cells were lysed and spun down until only cytosolic proteins are in the supernatent, what would be found in the sample of a healthy liver cell?
Transketolase
Cytosol = glycolysis, fatty acid synthesis, pentose phosphate pathway
In mitos = Beta ox, TCA cycle, decarboxylation of pyruvate
Transketolase is in pentose phosphate pathway and uses thiamine (B1) as a cofactor to shuttle 2C fragments between sugar molecules
A 4 day old presents with hypotonia and difficulty feeding. Elevated methylmalonic acid levels. What laboratory changes would be seen?
Increased Urine propionic acid, urine ketones, and serum ammonia
Decreased serum glucose
Methylmalonic acidemia = complete or partial deficiency of methylmalonyl-CoA mutase.
Complete def = lethargy vomiting and tachy in a newborn. Labs = hyperammonemia, ketotic hypoglycemia, and metabolic acidosis
Dx = elevated urine methylmalonic acid and propionic acid.
A pt has a deficiency in tetrahydrobiopterin synthesis. What else is likely to be deficient?
Serotonin
BH4 (tetrahydropterin) is a cofactor in the synthesis of tyrosine, DA, and serotonin
Can also be caused by dihydropteridine reductase deficiency.
Intelectual disability is the hallmark and results in NT deficiency and hyperphenylalanemia
Tx - low Phe diet and BH4 supplementation
2 y/o presents with easy bruising and hyperextensible skin.
Bx - adefect in extracellular processing of callagen.
Which step in synthesis is impaired?
N-term Propeptide removal
Ehlers-Danlos
procollagen peptidase deficiency causing impaired cleavage of terminal propeptides in the extracellular space.
Pts have joint laxity, hyperextensible skin, and tissue fragility due to formation of soluble collagen that does not properly crosslink
What are the steps in collagen synthesis
Collagen is a triple helix of alpha chains with a Gly-X-Y sequence (usually proline)
- N-term signal sequence facilitates ribosomal binding to the RER
- in the RER, signal sequence is cleaved and reveals the pro-alpha-cahin. Pro and Lys at the Y positions are hydroxylated
- Disulfide bonds are formed between alpha strands to form procollagen
- Procollagen is transported through Golgi into the extracellular space. The N and C term propeptides are cleaved by procollagen peptidases converting procollagen into less soluble tropocollagen
- Tropocollagen self-assemmbles into collagen fibrils. Lysly oxidase creates covalent crosslinks b/w collagen fibrils to form collagen fibers
Which molecule increases rate of reaction during muscle contraction?
Ca2+
A 22 y/o man presents with blistering on the back of his hands and forearms x years. Can develop large blisters that become hyperpigmented after rupturing. Vesicles and erosions on the dorsum of both hands. What is the enzyme deficiency?
Uroporphyrinogen decarboxylase
Early deficiency in porphyrin synthesis causes neuropsych without photosensitivity
Late step derangements = photosensitivity
Dx = Porphyria cutanea tarda - most common of the porphyras. Last step derangement. Usually acquiredmanifesting in the presence of susceptibility factors (alcohol, smoking, hydrocarbons, hepC, HIV).
An alocholic presents with necrosis of the mammillary bodies and gray matter surrounding the 3rd and 4th ventricles. Brain findings are associated with a decrease in?
RBC transketolase activity
Wernicke encephalopathy = ophthalmoplegia, ataxis, and confusion.
Chronic thiamine deficiency (B1) impairs glucose utilization in the CNS due to decreased activity of enzymes that require B1 as a cofactor.
Can dx a pt with thiamine deficiency if their baseline RBC transketolase activity is low, but increases after thiamine supplementation
Which enzyme is essential for the conversion of fructose-6-P to ribose-5-P in nucleic acid synthesis?
Transketolase
Pentose phosphate pathway
Transketolase is part of the nonoxidative branch (reversible) is responsible in pqart for the interconversion of ribose-5-P(nucleotide precursor) and Fructose-6-P (glycolysis intermediate)
A pt has an inability to oxidize very long chain fatty acids (VLCFA) and phytanic acid. Where is the defect?
Peroxisomes
Rare inborn error of metabolism.
These fatty acids are oxidized by beta oxidation (branched chain fatty acids such as phytanic acid) within peroxisomes. Commonly lead to neuro defects and improper CNS myelination
What biochemical feature explains the stretch and recoil of elastin?
Interchain cross-links involving lysine
Rubber-like property of elastin is due to the extensive cross-linking between elastin monomers which is facilitated by lysyl oxidase. Pts with alpha1-antitrypsin deficiency can develop early-onset lower lobe predominant emphysema due to excessive alveolar elastin degradation
Which molecule activates gluconeogenesis by increasing the activity of pyruvate carboxylase when it is abundant?
Acetyl-CoA
A pt presents with easy bruising and hyperextensible skin. Which step in collagen synthesis is impaired?
N-terminal propeptide removal
Ehlers-Danlos
Procollagen peptidase deficiency
Why does a pt with HbS have worse syx than a pt with HbC?
HbS allows hydrophobic interaction among hemoglobin molecules
Causes HbS polymerization of erythrocyte sickling
glutamic acid -> valine causes hydrophic interactions
40 y/o woman presents with fatigue x 3 months. She had a positive PPD 7 months ago and has been compliant with tx.
Hgb - 9
HCT - 28%
MCV - 72
Bone marrow stains with prussian blue. What enzyme is inhibited?
gamma-aminolevulinae synthase
Isoniazid inhibits pyridoxine phosphokinase causing B6 deficiency. Pyridoxine (B6’s) acitve form is the cofactor for gamma-aminolevulinate synthase which catalyzes the RLS in heme synthesis. Leads to sideroblastic anemia
Actin filaments in the I band are bound to structural proteins at which line?
Z line
Myosin filaments in the A band are bound to structural proteins in the?
M line
An RA pt with subQ nodules will likely have IgM Ab against?
The Fc portion of human IgG = rhematoid factor
Cartilage components serve as autoantigens that activate Cd4+Tcells which in turn stimulate B-cells to secrete Rheumatoid factor
Infant is born with flaccid lower extremities and absent ankle reflexes bilaterally. XR shows poorly developed lumbar spine and sacrum. The mother reports poor prenatal care. What probably happened?
Uncontrolled DM
Caudal regression syndrome = sacral agenesis causing lower extremity paralysis and urinary incontinence. Commonly associated with poorly controlled maternal DM
What is the most helpful way to monitor dz progression in a pt with ankylosing spondylotis?
Chest expansion - involvement of the thoracic spine and costovertebral and costosternal junctions can limit chest wall expansion -> hypoventilation
Other complications - ascending aortitis -> aortic dilation -> aortic insufficiency; anterior uveitis (pain, blurred vision, photophobia, and conjuntival erythema)
What post synaptic changes would be seen in myasthenia gravis
Reduced motor end-plate potential
A myasthenia gravis pt is treated but later presents with abd cramping, nausea, sweating, and diarrhea. What should she be given for the side effects?
Scopolamine
MG tx = cholinesterase inhibitors, immunosuppressants, and possible thymectomy.
Muscarine overstimulation leads to the side effects
A pt with MG presents with a thymic mass. This organ has the same embryologic origin as?
Inferior parathyroid glands
3rd pharyngeal pouch
A pt has lung cancer presents with hypercalcemia. Bone scan is negative for lytic lesions. What other finding is likely to be elevated in this pt.
Parathyroid hormone-related protein
Causes humoral hypercalcemia
PTHrP causes increased bone resorption and decreased renal excretion of calcium.
Ras is active when bound to ?
GTP
Cherry red Macula + normal abdominal exam
Tay Sachs
GM2 ganglioside accumulation
Even if only one of the 4 heme molecules are bound to CO, what happens?
Left shift because the other 3 hemes have a increased oxygen ability and decreased ability to unload O2 in the tissues
Excessive ingestion of egg whites can lead to a deficiency in?
Biotin (B7), avidin binds up biotin
Cofactor for carboxylase enzymes in (pyruvate -> OAA)
Syx = mental status change, myalgia, anorexia, derm changes
What are P bodies?
Cytoplasmic protein that plays an important role in mRNA translation, regulation, and degradation.
All other mRNA procesing steps occur in the nucleus
Pt presents with hypoglycemia after prolonged fasting and inappropriately low levels of ketones. What enzyme is he deficient in?
Impaired Beta oxidation
Acyl-CoA dehydrogenase deficiency most likely
G6PD is the RLS in the pentose phosphate pathway and catalyzes the conversion of?
G^P -> 6-phosphogluconolactone
Metabolism of 1g of: protein Carb Alcohol Fat Is how many calories
Protein - 4 cal
Carb - 4 cal
Alcohol - 7 cal
fat - 9 cal
Marfanoid kid with bilateral lens subluxation dies from a cerebrovascular accident. Kid would have benefited form?
Pyridoxine supplementation
Homocystinuria, cytathione synthatase deficiency, ar
Most common COD = thromboembolism
Respond to Pridoxine (B6) supplementation and methionine restriction
Activation of Gq dependent phospholipase C will cause a rise in?
Ca2+
PLC -> IP3, DAG -> PKC -> increased intracellular Ca2+
Scurvy syx are due to a defect in?
Proline and lysine hydroxylation in pro-collagen
Hydroxyproline and hydroxylysine are essential in collagen cross-linking
Propionic acid is derived from the metabolism of which aa’s?
Val, Ile, Met, and Thr
Also odd number fatty and cholesterol side chains
Defeciency of propionyl CoA carboxylase (propionyl CoA -> methylmalonyl CoA) causes propionic acidemia
Where is Glut 4 expressed?
Skeletal tissue and adipocytes. only glucose transporter that is responsive to insulin
GLUT 2 - Brain, intestine, RBC, kidney, liver, pancreas contastant expression
Why is frucotse metabolized quickly?
It enters glycolysis as G3P but it bypasses the glycolysis RLS PFK-1
Fructose comes from sucrose
Fructose is the only monosaccharide that bypasses PFK1
Organophosphates inhibit?
Cholinesterase. Accumulation of AcH in the synaptic terminal
Salivation, lacrimation, diaphoresis, bradycardia, bronchospasm
New born presents with vomiting and lethargy soon after breast feeding, jaundice, E. coli sepsis, renal disfunction (acidosis), cataract, hemolytic anemia. Dx?
Galactosemia
Defect in Galacotse -1-P uridyl transferase
Restrict breast feeding (Lactose = Galactose + glucose), switch to soy milk. Can improve cataracts, renal, and liver fxn
Soy = sucrose (glucose + fructose)
Pt presents with neuro syx and recurrent ab pain and responds to infusion of hemin. Dx and hemin downregulates?
Acute intermittent porphyria
AD, porphobilinogen deaminase deficiency
Hemin downregulates hepatic aminolevulinate synthase (RLS in heme synthesis)
In pKU, which aa becomes essential?
Tyrosine
Increased blood ammonia + urine orotic acid?
Ornithine transcarbamylase deficiency
Increased urine orotic acid but NL ammonia?
Uridine monophasphate synthetase deficiency
Also megaloblastic anemia that does not respond to b12 or Folate
What is on the 3’ end of tRNA?
CCA, sequence recognition for proteins and the OH group is the aa binding site
Look for a small RNA (70-90 residues) with lots of modified bases (hihydrouridine, ribothymidine)
What type of diet puts pts at risk for B12 deficiency?
Vegan
B12 is from animal products (meat, fish, dairy)
Need complete absence for 4-5 years before becoming symptomatic
Increased PRPP activity causes?
Gout
What signaling system does glucogan use in liver cells?
Adenylate cyclase
Activates adenylate cyclase -> converts ATP to cAMO -> activates Protein kinase A
PKA phosphorylates proteins in the regulatory regions of DNA
Function of carnitine?
Shuttles Acyl CoA (oxidized from fatty acid) into the mitochondria so that it can enter the TCA cycle Deficiency impares fatty acid transport from the cytoplasm into mitochondria (prevents Beta ox), decreases ketone production See myopathy (high creatine kinase, weakness, cardiac myopathy) and hypoketotic hypoglycemia.
Acetoacetates is?
Ketone body
Low in Primary carnitine deficiency
High in DKA
Cytosolic processes
Glycolysis
Fatty acid synthesis
Pentose phosphate pathway (transketolase)
Which 3 rxs are dependent on thiamine?
- alpha-ketoglutarate -> succinyl-CoA (alpha-Ketoglutarate dehydrogenase complex (TCA)
- Also Pyruvate -> acetyl CoA (pyruvate dehydrogenase) in glycolysis
- Transketolast (pentosephosphate pathway)
Ab highly specific for RA?
IgG against citrullinated peptides
Inflammation facilitates the conversion of Arginine to citulline which alters the shape of the protein
Which tissues cannot use ketones for energy?
RBCs (lack mitochondria)
Major amino acid responsible for transferring nitrogen to the liver:
Alanine (pyruvate + NH2)
Transfers amino groups to alpha-ketoglutarate to form glutamate. Glutamate is broken into urea by the liver.
Glutamine also because it is converted to alanine
Pts with defects in peroxisomes will have defects in?
Very long cains and branched fatty acids will not be able to undergo beta-ox
Zellweger syndrome - unable to form CNS myelin (hypotonia, seizures)
Alkaptonuria is caused by?
ar lack of homogentisic acid
Defect in tyrosine -> fumerate metabolism
Accumulation of homogentisic acid
Black urine, cartilage
Why would a DM pt be prescribed Fructose 2,6 bisphosphate
Activates PFK-1 to increase glycolysis
Inhibits F1,6-BPase (decrease gluconeogenesis)
Insulin activates the PFK-2 complex leading to increased Fructose-2,6-BP levels to augment glycolysis and inhibit gluconeogenesis (decreased alanine -> glucose)
How does isonizid cause fe deficient anemia?
Inhibits pyridoxine phosphokinase -> B6 deficiency
B6 is a cofactor for gamma-aminolevulinate synthase (RLS in heme synthesis) -> sideroblastic anemia
A lesch-nyhan pt will have increased activity of which enzyme?
PRPP
Defective HGPRT (purine salvage pathway)
X-linked
In TCA, GTP is synthesized from?
succinyl-CoA synthetase
succinyl CoA to succinate
GTP is used by phophoenol pyrubate carboxykinase during gluconeogenesis (phophoenolpyruvate from oxaloacetate)
Why does hyperammonemia cause neurologic syx?
Glutamine carries ammonia across the BBB and glutamine accumulates in the astrocytes. This decreases the amount of glutamine available for conversion to glutamate in the neurons
What are the chronic myeloproliferative disorders and what is the underlying pathology?
Polycytemia vera, essential thrombocytosis, primary myelofibrosis
Mutation in Janus Kinase 2 (JAK2), a cytoplasmic tyrosine kinase that becomes constitutively active and activates transcription proteins (STAT) in the absence of cytokines
tx - ruxolitinib (JAK 2 inhibitor)
What makes cyanide toxic?
Binds ferric iron (Fe3+) inhibiting cytochrome c oxidase in the mitochondria
Disrupts ETC
syx - reddish skin discoloration, tachypnea, HA, tachycardia, n/v, confusion, weakness
tx - inhaled amyl nitrite (increases fe3+ on Hgb to generate methemoglobin which has high affinity for cyanide sequestering it away from the mitos). Oh Hydroxycobalamin and sodium thiosulfate (break cyanide into nontoxic metabolites that are excreted in the urine)
Causes of anion gap metabolic acidosis
MUDPILES Methanol Uremia DKA Propylene glycol Isoniazid/Iron Lactic acidosis Ethylene glycos (antifreeze) Salicyclates (Aspirin)
Why does sickling occur in HbS?
Hydrophobic interaction among Hgb disrupts the normal nonpolar interactions between the Hgb tetramers
What is the fxn of leptin?
Acts on the arcuate nucleus of hypothalamus to inhibit production of neuropeptide Y (to decrease appetite) and stimulate production of alpha-MSH (increase satiety).
Mutation in leptin recepter = hyperphagia and obesity
Bloom syndrome is a mutation in?
Helicase
ar
BLM gene
Growth retardation, facial anomalies, photosensitive skin rash, immunodeficiency due to DNA breaks
Syx of Vitamin A toxicity?
Intracranial HTN (papilledema), skin changes, hepatosplenomegaly
Syx of Niacin deficiency?
3 D’s of pellagra
Dementia
Dermatitis
Diarrhea
Pt has pyruvate kinase deficiency. Why do they have splenomegaly?
Red pulp hyperplasia
Pyruvate kinase deficiency causes hemolytic anemia due to failure to generate ATP. Splenic hyperplasia occurs due to increased work of the splenic parenchyma which must remove the damaged RBCs
Lynch syndrome is?
Defect in mismatch repair
AD, MutS MutL
Colon, endometrial, and ovarian cancers
Following tx for Giardia, pt returns with steatorrhea. Why?
Secondary lactase deficiency
Occurs after inflammatory or infectious processes due to microvilli damage in the SI
Which enzyme synthesizes Epinepherine?
Phenylethanolabmine-N-methyltransferase (PMNT)
NE -> epi
Activated by cortisol
RLS in catecholamine synthesis?
tyrosine -> DOPA
Tyrosine hydroxylase
DOPA -> DA -> NE -> epi
In acute mesenteric ischemia there is lactic acidosis causing an anion gap acidosis. This is due to decreased activity of?
Pyruvate dehydrogenase
pyruvate -> acetyl co-A
Fxn of Pyruvate carboxylase?
Converts pyruvate to oxaloacetate in gluconeogenesis
Aortic root dilation and dissection is the most common COD in?
Marfan
Fibrilin-1 defect
Accumulation of molonyl-CoA inhibits?
Beta-oxidation of fatty acids in the well-fed state
beta ox occurs in the mitochondrial matrix
Malonyl-CoA inhibits carnitine acyltransferase to prevent the transfer of acyl groups into the mitochodria and prevent the breakdown of fatty acids
Neiman Pick causes an accumulation of?
Sphingomyelin
Cherry red macula, neuronal deficiencies, and splenomegaly
Sphingomyelinase deficiency
Lipid-laden foam cells
A pt has hypercalcemia, hyponatremia, and NL Parathyroid levels. Why?
Thiazide diuretics
What is a cofactor in OAA -> aspartate in the liver?
Pyridoxine
Transmination rx aa -> alpha keto acid.
Pyridoxine is a cofactor in transamination and decarboxylation rxns
alpha galactosidase deficiency
Fabry dz
Burning palms + renal failure, angiokeratomas and telangiectasis
X linked
Globotriaosylceramide accumulation
Pt with xanthomas and lipid laden macrophages. Lacks ApoE3 and ApoE4. What process is impaired?
Chylomicron remnant uptake by liver cells Familial dysbetalipproteinemia (type III), ar elevated cholesterol and triglycerides
Which mutation would allow a strain of E. coli to produce galactosidase despite being grown on a glucose only media?
Operator locus
Lac operon is regulated by two mechanisms:
1. Negative - repressor binding to the operator locus
2. Positive - cAMP-CAP binding upstream of the promoter
Constitutive expression of lack genes due to: impair binding of the repressor protein to the operator region
What property allows elastin to stretch and recoil?
Interchain cross-links with lysine
Lysyl oxidase
Which intracellular pathway is activated by Growth Hormone?
JAK-STAT pathway
GH -> binds to surface receptor -> activates JAK-STAT -> STAT goes to the nucleus and induces IGF-1 gene transcription
Cytokines and hematopoeitic factors also use the JAK-STAT pathway
Action of Vitamin C?
hydroxylation of proline and lysine residues in collagen synthesis
Which enzyme neutralizes toxic free radicals following muscle reperfusion?
Superoxide dismutase
If SOD can’t keep up -> acute compartment syndrome
Aldolase B deficiency
Hereditary fructose intolerance, ar
See hypoglycemia, FTT, jaundice, hepatomegaly when an infant is switched from breast feeding to solid foods
F1P accumulation inhibits gluconeogenesis -> hypoglycemia
Tx - restrict fructose and sucrose
Child presents with FTT and abudant quantities of multi-branched polysaccharides with abn short outer chains in the hpatocytes
Cori dz
Deficient in debranching enzyme
Unable to degrade a-1,6-glycosidic branch points
