Biochem Flashcards
Fabry’s disease
lysosomal storage disease
a-galactosidase A def->ceramide trihexoside
peripheral neuropathy, cardiovascular/renal disease
angiokeratomas on butt
Gaucher’s disease
lysosomal storage glucocerebrosidase def->glucocerebroside most common hepatosplenomegally, aseptic necrosis, anemia, thrombocytopenia Gaucher's cells (macrophages)
Niemann-Pick disease
lysosomal storage
phingomyelinase->sphingomyelin
progressive neurodegeneration, cherry red spot on macular foam cells
thrombocytopenia and worsening cognitive decline
Tay-Sachs
lysosomal
hexosaminidase A->GM2 ganglioside
progressice neurodegeneration, cheey red spot on macula, lysosomes with onion skin,
no hepatosplenomegaly
Krabbe’s disease
lysosomal
galactocerebrosidase->galactocerebroside
peripheral neuropathy, optic atrophy
affects myelin sheaths and occurs in very young
Metachromatic leukodystrophy
lysosomal
arylsulfatase A->cerebroside sulfate
central and peripheral demyelination with ataxia and dementia
Hurler’s syndrome
lysosomal
a-L-iduronidase->heparin sulfate, dermatan sulfate
gargoylism, corneal clouding
resembles dwarfism
Hunter’s syndrome
lysosomal
iduronate sulfatase->heparan sulfate, dermatan sulfate
mild Hurler’s and aggressive behavior, no corneal clouding
Von Gierkes (type I)
glycogen storage
glucose-6-phosphatase
severe fasting hypoglycemia, increased glycogen in liver and increased blood lactate
Pompe’s (type II)
glycogen
lysosomal a-1,4-glucosidase
cardiomegaly (Pompe’s trashes the pump)
Cori’s (type III)
glycogen debranching enzyme (a-1,6-glucosidase) milder form of type I with normal blood lactate
McArdle’s (type IV)
glycogen
skeletal muscle glycogen phosphorylase
increased glycogen in muscle, painful muscle cramps
5 substances needed to make a purine
glycine, aspartate, glutamine (GAG AAs)
tetrahydrofolate, CO2
purines are Pure As Gold (A, G)
4 substances needed to make a pyrimidine
aspartate, glutamate, CO2 and ATP (last 3 from carbamoyl phosphate)
CUT the PY
what is the rate limiting step in purine synthesis
carbamoyl phophate synthetase II
what is the rate limiting step in pyrimidine synthesis
glutamine PRPP amidotransferase
what are the carbon sources in purine and pyrimidine synthesis
purine: glycine, tetrahydrofolate, CO2
pyrimidine: aspartate and CO2
inhibits ribonucleotide reductase in purine synthesis
hydroxyurea
inhibits dihydrofolate reductase in purine synthesis
methotrexate and trimethoprim
inhibits thymidylate synthase in purine synthesis
5-fluorouracil
inhibits inosine monophosphate dehydrogenase in pyrimidine syntheses if guanine
mycophenolate
inhibits PRPP amidotransferase in pyrimidine synthesis
6-mercaptopurine
characteristic findings in orotic aciduria
inability to convert orotic acid to UMP
increase orotic acid in urine
no increase in ammonia (no hyperammonemia)
failure to thrive
megaloblastic anemia that cannot be corrected with B12 or folate
Tx: oral uridine administration
a boy with self mutilating behavior, intellectual disability and gout
Lesch-Nyhan syndrome
deficiency in HGPRT that increases uric acid
TX: allopurinol
orotic acid in the urine plus elevations in serum ammonia
OTC deficiency
megaloblastic anemia does not improve with B12 or folate
orotic aciduria
deficiency causes SCID
adenosine deaminase
silent mutation in DNA
tRNA wobble, same amino acid
missense DNA mutation
changed AA but similar protein structure
nonsense DNA mutation
early stop codon
DNA polymerase III reads and proofreads
reads: 5’-3’
proofreads 3’-5’ exonuclease
nucleotide excision repair
endonucleases repairs damaged bases due to UV light (pyrimidine dimers)
mutated in xeroderma pigmentosum
base excision repair
glycosylases recognize and remove damaged bases, then endonucleases remove sugar, polymerase adds new base, ligase joins
mismatch repair
corrects mismatch in newly synthesized strands
defect causes hereditary nonpolyposis colorectal cancer (HNPCC)
bloom syndrome
mutation of helicase
ataxia telangiectasia
dsDNA repair defect
stop codons
UGA
UAA
UAG
polyadenylation signal
AAUAAA
what amino acid frequently has more coding sequences in mRNA than are represented in final peptide
methionine (start codon normally spliced out)
lac operon regulation
CAP: binds when glucose is absent and promotes B-galactosidase transcription
lac operon: bound unless lactose is present. prevents transcription
where does aminoacyl-tRNA synthetase bind tRNA
the CCA at 3’ end
hypophosphatemic rickets
formerly vit D resistant rickets. x-linked dominant disorder where proximal tubule cannot reabsorb phosphate, so you get a rickets like presentation
myopathy and CNS disease with muscle biopsy that shows ragged red fibers. Seen in the maternal family line
mitochondrial myopathies
blotting procedures
Down South: southern is DNA with DNA probe
rude yankees: northern is RNA with DNA probe
western cattle: protein with Ab probe
ELISA
direct: known Ab to identify Ag
indirect: known Ag to identify Ab
target present = color change
promoter region
- 25 TATA box (Hogness)
- 75 CAAT box
Kluver-Bucy syndrome
bilateral amygdala lesion that leads to hyperorality, hypersexuality, and disinhibited behavior. hyperdocility and curiosity also seen
enzyme that catalyzes peptide bond formation in ribosome
peptidyl trasnferase
ATP yield
32 ATP if malate-aspartate shuttle is used (heart and liver)
30 ATP if glycerol-3-phosphate shuttle is used (muscle and brain)
clinical consequence of glycolytic enzyme deficiency
hemolytic anemia (RBC swelling and lysing)
enzymes responsible for increasing and decreasing intracellular levels of fructose-2,6-bisphosphotase
phosphofructokinase-2 (increases F-2,6-BP)
induced by insulin
fructose bisphosphotase (decreases F-2,6-BP)
induced by glucagon
regulators of pyruvate kinase
ATP and alanine are negative
F-1,6-BP is positive
RLS glycolysis
phosphofructokinase-1 (PFK-1)
+ AMP and F-2,6-BP
- ATP and citrate
RLS gluconeogenesis
F-1,6-BP
+ATP
- AMP and F-2,6-BP
RLS TCA cycle
isocitrate dehydrogenase
+ ADP
- ATP and NADH
RLS glycogen synthesis
glycogen synthase
+ glucose, insulin
- epinephrine, glucagon
RLS glycogenolysis
glycogen phosphorylase
+ AMP, epinephrine, glucagon
- insulin, ATP
RLS HMP shunt
G-6-PD
+ NADP+
- NADPH
RLS de novo pyrimidine synthesis
carbamoyl phosphate synthetase II
RLS de novo purine synthesis
glutamine-PRPP amidotransferase
- AMP, IMP, GMP
RLS urea cycle
carbamoyl phosphate synthetase I (mitochondria)
+ N-acetylglutamate
RLS fatty acid synthesis
acetyl-CoA carboxylase (ACC)
+ insulin, citrate
- glucagon, palmitoyl-CoA
RLS fatty acid oxidation
carnitine acyltransferase I (carnitine palmitoyl transferase-I)
- malonyl-CoA
RLS ketogenesis
HMG-CoA synthase
RLS cholesterol synthesis
HMG-CoA reductase
+ insulin, thyroxine
- glucagon, cholesterol
irreversible enzymes in gluconeogenesis
pyruvate carboxylase
PEP carboxykinase
F-1,6-BP (RLS)
glucose-6-phophatase
energy available to fuel endergonic reactions
glucose>pyruvate>ATP>AMP>adenosine
Gibbs free energy
dG = dH-TdS
how does glucagon increase glycogenolysis
glucagon-> cAMP -> protein kinase A -> + glucagon phosphorylase kinase -> + glycogen phosphorylase (RLS)
glycogen phosphorylase deficiency
McArdle’s
glucose-6-phophatase deficiency
Von Gierke’s
lactic acidosis, hyperlipidemia, hyperuricemia (gout)
Von Gierke’s
a-1,6-glucosidase deficiency
Cori’s
a-1,4-glucosidase deficiency
Pompe’s
cardiomegaly
Pompe’s (infantile)
diaphragm weakness leading to respiratory failure
Pompe’s (adult)
increased glycogen in liver, severe fasting hypoglycemia
Von Gierke’s
hepatomegaly, hypoglycemia, hyperlipidemia (normal kidneys, lactate, and uric acid)
Cori’s
painful muscle cramps, myoglobinuria with strenuous exercise
McArdle’s
severe hepatosplenomegaly, enlarged kidneys
Von Gierke’s
what is potential fates of pyruvate
acetyl CoA
oxaloacetate
alanine
lactate
what is purpose of Cori cycle
take lactate from RBC and muscles to liver to regenerate glucose. requires 6 ATP
what is purpose of alanine cycle
transport amine groups to the liver
ALT and AST play a role here
what is required by all aminotransferases
B6 (pyridoxal phosphate)
major regulatory enzymes in TCA
citrate synthase
isocitrate dehydrogenase
a-ketoglutarate dehydrogenase
energy output of TCA
3 NADH, 1 FADH2, 1 GTP = 10 ATP for each acetyl CoA
multiply by 2 for each glucose molecule
what substances cause uncoupling of ATP synthesis by increasing the permeability of the inner mitochondrial membrane
aspirin
2,4-DNP
thermogenin
what tissues use the pentose phosphate shunt
RBC
liver
adrenal cortex
mammary glands
symptoms of classic galactosemia
failure to thrive, mental retardation, jaundice, hepatomegaly, infantile cataracts
deficiency of galactokinase
galactokinase deficiency
results in build up of galactitol in blood and urine-> infantile cataracts
deficiency of aldolase B
fructose intolerance
F-1-P accumulates and causes a decrease in phosphate -> inhibition of glycogenolysis and gluconeogenesis
hypoglycemia, jaundice, cirrhosis, vomiting
deficiency of lactase
lactose intolerance
deficiency of galactose-1-phosphate uridyltransferase
classic galactosemia
accumulation of toxic substances
deficiency of fructokinase
essential fructosuria
asymptomatic
fructose in blood and urine
why does ethanol metabolism cause hypoglycemia
NAD+ is regenerated by the liver by transferring pyruvate -> lactate and oxaloacetate -> malate
this shuts down gluconeogenesis
hallmark features of kwashiokar
FLAME fatty liver anemia malnutrition edema
when does synthesis of ketone bodies occur
when production of acetyl CoA exceeds the capacity of the TCA cycle
refeeding syndrome
drop in Mg, K and phosphate due to cells taking up these vitamins from the blood. can cause arrhythmias
which deficiency causes familial hypercholesterolemia
def of LDL receptors
which deficiency causes hyperchylomicronemia
lipoprotein lipase def or altered C-II
abetalipoproteinuria
mutation in microsomal triglyceride transfer protein (MTP) decreases B-48 and B-100
activates LCAT
apo A-1
mediates chylomicron secretion
apo B-48
mediates VLDL secretion
apo B-100
binds to LDL receptor
apo B-100
cofactor for lipoprotein lipase
apo C-II
mediates uptake of remnant particles
apo E
repository for apoC and apoE
HDL
basic AA
Arg, Lys, His
Histidine is actually neutral at body pH
acidic AA
Asp and Glu
what is most common urea cycle deficiency
orntithin transcarboxylase deficiency: first enzyme in loop. Buildup of carbamoyl phosphate that leads to hepatoencephalopathy (tremor, slurring speech, somnolence, cerebral edema, blurring vision)
vit B6 is needed as a cofactor to make
dopamine, niacin, histamine, porphyrin (heme) and GABA
what AA is precursor for: histamine porphyrin NO GABA s-adenosyl-methionine creatine niacin/serotonin
histidine glycine arginine glutamate methionine arginine tryptophan
PKU
deficiency of phenylalanine hydroxylase or the tetrahydrobiopterin cofactor
musty odor due to aromatic amino acid buildup (phenylalanine)
mental retardation, growth retardation, seizures, fair skin, eczema
Alkaptonuria
deficiency of homogentisic acid oxidase
buildup of tyrosine: dark urine and connective tissue
brown pigmented sclera
albinism
defect in tyrosinase (melanin production) or defective tyrosine transporters
can also be a failure of neural crest cells to migrate
homocystinuria
3 forms:
cystathionine synthase def.
decreased affinity of cystathionine synthase for pyridoxal phosphate (B6)
homocysteine methyltransferase def (requires B12)
mental retardation, downward lens subluxation, atherosclerosis
SAM
transfers methyl units
needed for conversion of NE to epi
requires B12 and folate
cystinuria
renal amino acid transporter defect: staghorn calculi in kidney from excess AA.
maple syrup urine disease
blocked branched amino acid breakdown (isoluecine, leucine, valine) due to a-ketoiacud dehydrogenase deficiency
severe CNS defects
Hartnup disease
defective neutral amino acid transporter on renal and intestinal cells. tryptophan excretion
leads to pellagra (niacin deficiency)
G- rods in a neonate with pneumonia
E. coli
G+ cocci in neonate with pneumonia
group B strep
G+ cocci in pairs
strep pneunomiae
G+ cocci in clusters
s. aureus
iron poisoning
peroxidation of membrane lipids
acute: gastric bleeding, hypovolemic shock
chronic: metabolic acidosis, scarring of GI system (obstruction)
zinc deficiency
lack of zing fingers, a transcription factor motif
delayed wound healing, decreased adult hair, anosmia, dysgeusia
rash around eyes, mouth, anus (acrodermatitis enteropathica)
impaired night vision and infertility
lead poisoning
inhibits ferrochelatase
decrased IQ, hearing problems, lead lines, wrist and foot drop, anemia
treat with succimer and EDTA
dimercaprol if really bad
mercury poisoning
accumulates in kidney and brain
acrodynia: peeling of fingertips
abdominal pain
bluish-colored lines on the gingivae
lead poisoning (Burton’s lines)
fat soluble vitamins are dependent on what for absorption
ileum and pancreas
vit D
D2 = orgocalciferol (plants)
D3 = cholecalciferol (milk and sun exposure)
25-hydroxycholecalciferol (converted by 25 hydroxylase)
1,25-(OH)2D3 (calcitriol) is active form (converted by 1ahydroxylase)
vit A use
measles and AML, subtype M3 in developing world
high levels of vit A
liver and leafy vegetables
vit E
alpha tocopherol
prevents non-enzymatic oxidation
def: muscle weakness, posterior column and spinocerebellar tract demyelination
symptoms of vit A toxicity
visual impairment, fatigue, ataxia, HA, increased intracranial pressure, dry skin, alopecia, hepatotoxicity, athralgia
scurvy symptoms
sore, spongy gums, loose teeth
fragile blood vessels: hemorrhages
swollen joints, impaired wound healing
anemia
vit c hydroxylates which AA
lysine and proline
vit B1 needed as cofactor for
pyruvate dehydrogenase (glycolysis to TCA)
a-ketoglutarate dehydrogenase
transketolase (HMP shunt)
branched chain amino acid dehrydrogenase
thiamine deficiency
damage to medial thalamus and mammillary bodies
cerebral atrophy
Wernicke-Korsakoff syndrome
Wernicke: acute encephalopathy, oculomotor dysfunction, gait ataxia
Korsakoff: memory loss, confabulation, apathy
long term consequence of Wernicke
beriberi
thiamine deficiency
wet: heart: high-ouput cardiac failure, edema
dry: polyneuritis, muscle wasting (wrist drop)
riboflavin
B2 cofactor for oxidation and reduction 2 forms: flavin mononucleotide (FMN) flavin adenine dinucleotide (FAD) def: cheolosis
niacin
B3 2 forms: NAD and NADP derived from tryptophan def: pellagra (dermatitis, dementia, diarrhea) INH causes deficiency
vit B6
pyridoxal phosphate
cofactor in transamination, decarboxylation, and glycogen phosphorylase
def: convulsions, neuropathy, sideroblastic anemia
INH causes def
vit B7
biotin
carboxylation enzymes
B9
folic acid
converted to tetrahydrofolate (THF)
deficiency: alcoholism and pregnancy, medications
most common def. in US
B12
cobalamin
cofactor for homocysteine methyltransferase and methylmalonyl-CoA mutase
abnormal myelination in deficiency
use Schilling test to detect etiology of def.
pernicious anemia
immune destruction of parietal cells and Ab to IF that leads to decrease in B12 levels
pt presents with convulsions and irritability. what vit def?
vitamin B6
peripheral neuropathy, glossitis
B12, B6
neural tube defects
folate
dermatitis, diarrhea, dementia
B3 (niacin)
megaloblastic anemia
B12, folate
pernicious anemia
B12
used in oxidation/reduction rxns
B2 (riboflavin), B3
used in carboxylation rxns
biotin
requires intrinsic factor for absorption
B12
used by pyruvate dehydrogenase and a-ketoglutarate dehydrogenase
B1 (thiamine)
can be used to elevate HDL and lower LDL
B3 (niacin)
deficiency can be caused by isoniazid use
B6 (pyridoxine), B3 (niacin)
cobalt is found in vitamin
B12 (cobalamin)
critical for DNA synthesis
folate (B9), B12
most common vit def in US
folate
hypersegmented neutrophils
B12 or folate def
dilated cardiomyopathy, edema, and polyneuropathy
B1 (wet beriberi thiamine def)
