metabolism Flashcards
mitochondria
beta oxidation acetyl CoA production TCA cycle ox phos ketogenesis
cytoplasm
glycolysis fatty acid synthesis HMP shunt protein synthesis (RER) steroid synthesis (SER) cholesterol synthesis
both mito and cyto
heme synthesis
urea cycle
gluconeogenesis
kinase
uses ATP to add phosphate
phosphorylase
adds inorganic phosphate onto substrate w/o ATP
phosphatase
removes phosphate
dehydrogenase
catalyzes oxidation-reductions rxn
hyrdoxylase
adds hydroxyl (-OH)
Carboxylase
transfers CO2 w/help of biotin
mutase
relocates fnx grp w/in molecule
glycolysis rate-limiting step enzyme
phosphofructokinase
gluconeogenesis rate-limiting step enzyme
fructose 1,6 bisphosphatase
TCA cycle rate-limiting step enzyme
isocitrate dehydrogenase
glycogenesis rate-limiting step enzyme
glycogen synthase
glycogenolysis rate-limiting step enzyme
glycogen phosphorylase
HMP shunt rate-limiting step enzyme
carbamoyl phosphatate synthetase
De novo pyrimidine synthesis rate-limiting step enzyme
carbamoyl phosphate synthetase II
de novo purine synthesis rate-limiting step enzyme
glutamine-PRPP amidotransferase
ureas cycle rate-limiting step enzyme
carbamoyl phosphate synthetase I
FA synthesis rate-limiting step enzyme
acetyl-CoA carboxylase (ACC)
FA oxidation rate-limiting step enzyme
carnitine acyltransferase I
ketogenesis
HMG-CoA synthase
Cholesterol synthesis
HMG-CoA reductase
arsenic
glycolysis -> zero net ATP inhibits lipoic acid vomiting rice-water stool garlic breath
NAD
electron acceptor
usually catabolic processes
NADPH
electron acceptor
used in anabolic processes
hexokinase
phosphorylation of glucose - G6P
1st step of glycolysis and glycogen synthesis
expressed in most tissues except liver and beta cells
higher affinity/lower Km then glucokinase
lower capacity/Vmax then glucokinase
not induced by insulin
inhibited by G6P
gene mutation NOT associated w/ MODY
glucokinase
phosphorylation of glucose - G6P 1st step of glycolysis and glycogen synthesis expressed in liver and beta cells lower affinity/higher Km then hexokinase higher capacity/Vmax then hexokinase IS induced by insulin NOT inhibited by G6P gene mutation IS associated w/ MODY
which glycolysis enzymes require ATP?
hexokinase/glucokinase
phosphofructokinase-1 (RLS)
which glycolysis enzymes produce ATP?
phosphoglycerate kinase
pyruvate kinase
fructose 2.6 bisphosphonate
FBPase-2 and PFK-2 are same enzyme whose direction is reversed by phosphorylation via PKA
fasting: increased glucagon -> increased cAMP -> increased PKA -> increased FBPase 2 -> less glycolysis or gluconeogenesis
fed: increased insulin -> decreased cAMP -> decreased PKA -> increased PFK-2 -> more glycolysis and less gluconeogenesis
pyruvate dehydrogenase complex
mito enzyme complex linking glycolysis and TCA cycle (active in fed state)
pyruvate + NAD + CoA -> acetyl CoA + CO2 + NADH
activated by exercise which increases NAD, ADP, and Ca
pyruvate dehydrogenase complex deficiency
x-linked
build-up of pyruvate -> lactate and alanine
neuro defects, lactic acidosis, increased serum alanine starting in infancy
Tx of pyruvate dehydrogenase complex deficiency
increase intake of ketogenic nutrients
high fat
lysine and leucine
pyruvate can become what?
alanine (via ALT for Cahill cycle)
oxaloacetate (via PC for TCA cycle or gluconeogenesis)
acetyl-CoA (via PDH for TCA cycle)
Lactate ( via LDH for Cori Cycle)
TCA cycle
Citrate Is Krebs Starting Substrate For Making Oxaloacetate citrate isocitrate alpha-KG succinyl CoA succinate fumarate malate oxaloacetate
rotenone
blocks complex I of ETC
antimycin A
blocks complex III of ETC
cyanide
blocks complex IV of ETC
CO
blocks complex IV of ETC
Oligomycin
blocks complex V(ATP synthase) of ETC
uncoupling agents
2,4 dinitrophenol
aspirin
thermogenin in brown fat
gluconeogenesis irreversible enzymes
Pathway Produces Fresh Glucose pyruvate carboxylase phosphoenolpyruvate carboxykinase fructose 1,6 bisphosphatase glucose 6 phosphate
pyruvate carboxylase
in mito
pyruvate -> oxaloacetate
phosphoenolpyruvate carboxykinase
in cytosol
oxaloacetate -> phophoenolpyruvate
fructose 1,6 bisphosphatase
in cytosol
fructose 1,6 bisphosphate -> fructose 6 phosphate
glucose 6 phosphatase
in ER
G6P -> glucose
HMP shunt/pentose phosphate pathway
provides source of NADPH from G6P
yields ribose for nucleotide synthesis
NO ATP used or produces
occurs in lactating mammary glands, liver, adrenal Cx
oxidative rxn
use NADP+
create and inhibited by NADPH
produce CO2
irreversible
nonoxidative rxns
reversible
G6PD deficiency
XR MC human enzyme deficiency more prevalent in blacks increases malarial resistance G6PD required to replenish NADPH which is needed for glutathione reductase
G6PD presenation
hemolytic anemia following favao beans, sulfonamides, primaquine, atnituberculosis drugs, or infection
G6PD PBS
heinz bodies- denatured hemoglobin precipitates in RBCs
bite cells- results from phagocytic removal of Heinz bodies
‘Bite into some Heinz ketchup on fava beans’
essential fructosuria
defect in fructokinase- AR
benign asymptomatic condition since fructose not tapped in cells
fructose in blood and urine
fructose intolerance
AR
deficiency of aldolase B
fructose-1-phosphate accumulates -> decreased bioavailability of phosphate -> inhibition of glycogenolysis and gluconeogenesis
urine dip stick neg
symptoms of fructose intolerance
hypoglycemia, jaundice, cirrhosis, vomiting
Tx of fructose intolerance
decrease fructose and sucrose in diet
galactokinase deficiency
galactitol accumulates if galactose in diet
mild
AR
symptoms of glactokinase deficiency
galactose in blood and urine
infantile cataracts
failure to track objects or develop a social smile
classic galactosemia
absence of galactose-1-phosphate uridyltransferase
AR
accumulation of toxic substances in lens of eye
symptoms of classic galatosemia
failure to thrive jaundice hepatomegaly infantile cataracts intellectual disability E. coli sepsis
Tx of classic galactosemia
exclude galactose and lactose from diet
sorbitol
glucose can be converted to sorbitol vis aldose reductase
can then be converted to fructose via sorbitol dehydrogenase
sorbitol dehydrogenase deficiency
intracellular sorbitol accumulation -> osmotic damage (cataracts, retinopathy, peripheral neuropathy)
seen in DM
primary lactase deficiency
age dependent decline after childhood
common in asian, african, or native american descent
secondary lactase deficiency
loss of BBE d/t gastroenteritis, autoimmune disease, etc…
congenital lactase deficiency
rare
defective gene
lactase deficiency
lactase usually breaks lactose into glucose and galactose
stool decreased pH
breath shows increased hydrogen
symptoms of lactase deficiency
bloating, cramps, flatulence, osmotic diarrhea
glucogenic essential AAs
methionine (Met)
Valine (Val)
Histadine (His)
gluconeogenic/ketogenic essential AAs
isoleucine (Ile)
pheylalanine (Phe)
threonine (Thr)
tryptophan (Trp)
ketogenic essential AAs
leusine (Leu)
lysine (Lys)
acidic AAs
aspartic acid (Asp) Glutamic acid (Glu)
basic AAs
arginine (Arg) lysine (Lys) histadine (His) Arg and Lys in histones Arg and His needed during growth
urea cycle
excess nitrogen converted to urea
Ordinarily Careless Crappers Are Also Frivolous About Urination
Ornithine + Carbamoyl phosphate -> Citrulline
Citrulline + Aspartate -> Arginosuccinate -> Fumarate +Arginine
Arginine -> Urea +Ornithine
hyperammonemia
excess NH4 -> depletes alpha ketoglurarate -> inhibits TCA cycle
tremor, slurring of speech, somnolence, vomiting, cerebral edema, blurring of vision
Tx of hyperammonemia
limit protein in diet
lactulose -> acidifies GI tract to trap NH4
Rifaximin -> decrease colonic ammoniagenic bacteria
benzoate or phelbutyrate -> bind AAs
N-acetylglutamate synthase deficiency
required cofactor for carbamoyl phosphate snthetase I -> hyperammonemia
presents in neonates as poorly regulated resp and body temp, poor feeding, developmental delay, intellectual disability
ornithine transcarbamylase deficiency
MC urea cycle disorder
XR (other urea cycle disorders AR)
usually presents first few days of life, but may be later
excess carbamoyl phosphate is converted to orotic acid
findings in ornithine transcarbamylase deficiency
increased orotic acid in blood and urine
decreased BUN
symptoms of hyperammonemia
NO megaloblastic anemia in contrast to orotic aciduria
pheylketonruia
AR
d/t decreased phenylalanine hydroxylase or decreased tetrahydrobiopterin cofactor (malignant PKU)
increased phenylalanine -> pheylketones in urine
findings of PKU
normal at birth b/c of maternal enzyme intellectual disability growth retardation seizures fair skin eczema musty body odor
Tx of PKU
decreased phenylalanine and increased tyrosine in diet
tetrahydrobiopterin supplementation
cannot eat aspartame
PKU memory jog
disorder of aromatic aa meta -> musty body odor
maternal PKU
lack of proper dietary therapy during prego
findings in infant -> microcephaly, intellectual disability, growth retardation, congenital heart defects
maple syrup urine disease
AR
blocked degresation of brr aa (isoleucine, leucine, and valine) d/t decreased alpha ketoacid dehydrogenase
symptoms of maple syrup urine disease
severe CNS defects
intellectual disability
death
urine smells like maple syrup/burnt sugar
Tx of maple syrup urine disease
restriction of isoleucine, leucine, and valine in diet
thiamine supplementation
maple syrup urine disease pneumonic
I Love Vermont maple syrup from maple trees w/Brr
Alkaptnuria/ochronosis
AR, usually benign
deficiency of homogentisate oxidase in degradative pathway of tyrosine to fumarate-> pigment forming homogentisic acid accumulates in tissues
alkaptnuria/ochronosis findings
dark CT
brown pigmented sclera
urine turns black on prolonged exposure to air
may have debilitating arthralgias
homocystinuria
all types AR excess homocysteine in urine intellectual disability osteoporosis marfanoid habitus kyphosis lens subluxation thrombosis and atherosclerosis
cystinuria
AR, common defect of renal PCT and intestinal aa transport prevents reabsorption of COLA hexagonal cystine stones urinary cyanide-nitroprusside test Dx
COLA
cysteine
ornithine
lysine
arginine
cystinuria Tx
chelating (pencicillamine)
hydration
glycogen storage diseases
all AR Very Poor Carb Meta Von Gierke's disease (type I) Pompe (type II) Cori (type III) McArdle (type V)
Von Gierke’s what enzyme?
G6P
AR
Von Gierke’s findings
severe fasting hypoglycemia big increase in glycogen in liver increased blood lactate increased TGs increased uric acid hepatomegaly
Von Gierke’s Tx
frequent oral glucose/cornstarch
avoid fructose and galactose
Pompe what enzyme?
lysosomal alpha 1,4 glucosidase (acid maltase)
AR
Pompe findings
cardiomegaly/hypertrophic cardiomyopathy
exercise intolerance
systemic findings -> early death
Pompe acronym
Pompe trashes the Pumps (heart, mm, liver)
cori disease what enzyme?
debrr/alpha-1,6 glucosidase
cori disease findings
milder form of type I w/normal blood lactate levels, gluconeogenesis intact type I: severe fasting hypoglycemia big increase in glycogen in liver increased blood lactate increased TGs increased uric acid hepatomegaly
McArdles disease
increase glycogen in mm
but mm cannot break it down -> painful mm cramps
myoglobinuria w/strenuous exercise
arrhythmia from electrolyte abnormalities
blood glucose typically normal
McArdles enzyme
skeletal mmm glycogen phosporylase/myophosphorylase
McArdles Tx
vit B6 (pyridoxine)
Fabry disease
XR
deficient alpha galactosidase
accumulates ceramide trihexoside
fabry findings
peripheral neuropathy hands/feet
angiokeratomas
cardiovascular/renal disease
gaucher disease
AR
deficient glucocerebrosidase
accumulates glucocerebroside
most common lysosomal storage disease
gaucher findings
hepatosplenomegaly pancyotpenia osteoporosis aseptic necrosis of femur bone crises gaucher cells (lipid laden macros resembling crumpled tissue paper)
gaucher Tx
recombinant glucocerebrosidase
Niemann pick disease
AR
deficient spingomyelinase
accumulates spingomyelin
niemann pick findings
progressive neurodegeneration
hepatosplenomegaly
foam cells
cherry red spot on macula
tay-sachs disease
AR
deficient hexosamindase A
accumates GM2 ganglioside
tay sachs findings
progressive neurodegeneration developmental delay cherry red spot on macula lysosomes w/onion skin NO hepatosplenomegaly
krabbe disease
AR
deficient galactocerebrosidase
accumulates galactocerebroside and psychosine
krabbe disease findings
peripheral neuropathy
developmental delay
optic atrophy
globoid cells
metachromatic leukodystrophy
AR
deficient in arylsulfatase A
accumulates cerebroside sulfate
metachromatic leukodystrophy
central and peripheral demyelination w/ataxia and dementia
hurler syndrome
AR
deficient alpha-L-iduronidase
accumulates heparan sulfate
hurler syndrome findings
developmental delay gargoylism airway obstruction corenal clouding hepatosplenomegaly
hunter syndrome
XR
deficient iduronate sulfatase
accumulates heparan sulfate and dermatan sulfate
hunter syndrome findings
mild hurler + aggression
no corneal clouding
Niemann picks acronym
No man picks his nose w/his sphinger (sphingomyelinase)
Tay-sachs acronym
Tay-SaX lacks heXosaminidase
Hunters syndrome acronym
Hunters see clearly (no corneal clouding) and aggressively aim for the X (XR)
which lysosomal diseases assocaites w/Ashkenazi Jews
Tay-Sachs
Niemann picks
gaucher
systemic primary carnitine deficiency
defect in transport of LCFA into mito
toxic accumulation
weakness, hyptonia, and hypoketotic hypoglycemia
medium chain acryl-CoA dehydrogenase deficiency
AR
cannot break down FAs into Acetyl CoA
accumulation of 8-10 carbon fatty acyl carnitines in blood
hypoketotic hypoglycemia
medium chain acryl-CoA dehydrogenase deficiency presentation
infancy- early childhoos
vomiting, lethargy, seizures, coma, liver dysfunction
may cause sudden death, must avoid fasting
1g protein or fat
4kcal
1g fat
9kcal
1g alcohol
7kcal
cholesterol synthesis RLE
HMG-CoA reductase (induced by insulin) converts HMG-CoA -> mevalonate
LPL
lipoprotein lipase
degradation of TGs circulating in chylomicrons and VLDLs
on vascular endo surface
HL
hepatic lipase
degradation of TGs remaining in IDL
Hormone-sensitive lipase
degradation of TGs stored in adipocytes
LCAT
catalyzes esterification of cholesterol
apolipoprotein E
mediates remnant uptake
found on chylomicron, chylomicron remnant, VLDL, IDL, HDL
apoplipoprotein A-I
activates LCAT
found on chylomicron and HDL
apoplipoprotein C-II
lipoprotein lipase cofactors
found on chylomicron, VLDL, HDL
apoplipoprotein B-48
mediates chylomicron secretion
found on chylomicron, chylomicron remanant
apoplipoprotein B-100
binds LDL R
found on VLDL, IDL, LDL
LDL
transports cholesterol from liver to tissues
HDL
transports cholesterol from periphery to liver
acts as repository for apoplipoprotein C and E (needed for chylomicron and VLDL meta) secreted both from liver and intestines
alcohol increases synthesis
chylomicron
delivers dietary TGs to periphery
delivers cholester to liver in form of chylomicron remnant
secreted by intestinal epi
VLDL
delivers hepatic TGs to periphery
secreted by liver
IDL
formed in degradation of VLDL
delivers TGs and cholesterol to liver
LDL
delivers hepatic cholesterol to peripheral tissues
formed by hepatic lipase modification of IDL in periphery
taken up by target cells via R mediated endocytosis
familial dysplipidemia type I
hyper-chylomicronemia
increased chylomicrons, TGs, and cholesterol in blood
creamy layer in supernatant
AR
path of familial dysplipidemia type I
lipoprotein lipase deficiency or altered apolipoprotein C-II
causes pancreatitis, hepatosplenomegaly, eruptive/pruitic xanthoms
no increased risk for atherosclerosis
familial dyslipidemia type IIa
familial hypercholesterolemia
increased LDL, cholesterol
AD
path of familial dyslipidemia type IIa
absent or defective LDL R
heterozyogotes have cholesterol 300+
homozygotes have cholesterol 700+ (rare)
accelerated atheroscloersis (MI
familial dyslipidemia type IV
familial hypertriglyceridemia
increased VLDL, TG
AD
path of familial dyslipidemia type IV
hepatic overproduction of VLDL
TGs >1000 can cause acute pancreatitis
