Metabolism Flashcards
site of FA oxidation (beta oxidation), acetyl-CoA production, TCA cycle, oxidative phosphorylation, ketogenesis
mitochondria
site of glycolysis, FA synthesis, HMP shunt, protein synthesis (RER), steroid synthesis (SER), cholest synthesis
cytoplasm
site of heme synthesis, urea cycle, gluconeogenesis
both mitochondria & cytoplasm
‘HUGs take 2’
phosphofructokinase-1
glycolysis
fructose-1,6-bisphosphatase
gluconeogenesis
isocitrate dehydrogenase
TCA cycle
glycogen synthase
glycogenesis
glycogen phosphorylase
glycogenolysis
glucose-6-phosphate dehydrogenase (G6PD)
HMP shunt
carbamoyl phosphate synthetase II
de novo pyrimidine synthesis
glutamine-phosphoribosylpyrophosphate (PRPP) amidotransferase
de novo purine synthesis
carbamoyl phosphate synthetase I
urea cycle
acetyl-CoA carboxylase
fatty acid synthesis
carnitine acyltransferase I
fatty acid oxidation
HMG CoA synthase
ketogenesis
HMG CoA reductase
cholesterol synthesis
what causes glycolysis to produce zero net ATP
arsenic
NADH, NADPH, FADH2 carry ____ in activated form
electrons
CoA & lipoamide carry ____ in activated form
acyl groups
biotin carries ____ in activated form
CO2
tetrahydrofolates carry ____ in activated form
1-C units
S-adenosylmethionine carries ____ in activated form
CH3 groups
TPP carries ____ in activated form
aldehydes
universal electron acceptors
NAD+ from vitB3
FAD+ from vitB2
NAD+ is used in what type of processes
catabolic - carries reducing equivalents away as NADH
NADPH is used in what type of processes
anabolic - steroid & fatty acid synthesis as a supply of reducing equivalents
also used in resp burst, cytochrome P450 system, glutatione reductase
locations of hexokinase
most tissues except liver and pancreatic beta cells
locations of glucokinase
liver & beta cells of pancreas
function of hexokinase
sequesters glucose in tissues at low glucose (low insulin)
function of glucokinase
stores glucose in liver if high conc of glucose
gene mutation assoc with maturity onset diabetes of young
glucokinase
what inhibits lipoic acid causing vomiting, rice water stools, garlic breath?
arsenic
what enzyme is responsible for carrying amino groups to the liver from muscle
alanine aminotransferase (B6)
what enzyme creates oxaloacetate which replenishes TCA cycle or used in gluconeogenesis
pyruvate carboxylase (biotin)
what enzyme transitions from glycolysis to TCA cycle
pyruvate dehydrogenasae (B1, B2, B3, B5, lipoic acid)
what enzyme is at end of anaerobic glycolysis (major pathway in RBCs, WBCs, kidney medulla, lens, testes, cornea)
lactic dehydrogenase (B3)
glycolysis produces what?
glucose to pyruvate
TCA cycle produces what?
pyruvate to acetylCoA
cofactors required for alpha ketoglutarate dehydrogenase complex & pyruvate dehydrogenase complex
B1, B2, B3, B5, lipoic acid
oxidative phosphorylation poisons- directly inhib e- transport causing decr proton gradient and block ATP synthesis
Rotenone, cyanide, antimycin A, CO
oxidative phosphorylation poison- directly inhib mito ATP synthase causing incr proton gradient - no ATP produced
oligomycin
oxidative phosphorylation poison- incr perm of membrane causing decr proton gradient and incr O2 consumption - ATP synthesis stops but e- transport continues - produces heat
2,4-dinitrophenol (illicit used for wt loss)
ASA (fevers with ASA overdose)
thermogenin in brown fat
enzyme in mito used to convert pyruvate to oxaloacetate
requires biotin & ATP
pyruvate carboxylase (gluconeogenesis)
enzyme in cytosol used to convert oxaloacetate to phosphoenolpyruvate
requires GTP
phosphoenolpyruvate carboxykinase (gluconeogenesis)
enzyme in cytosol used to convert fructose 1,6 bisphosphate to fructose 6 phosphate
fructose 1,6 bisphosphatase (gluconeogenesis)
enzyme in ER used to convert glucose 6 phosphate to glucose
glucose 6 phosphatase (gluconeogenesis)
denatured Hb precipitates in RBCs due to oxidative stress
seen in G6PD deficiency
heinz bodies
result of phagocytic removal of Heinz bodies by splenic macrophages
seen in G6PD deficiency
bite cells
defect in fructokinase, autosomal recessive, benign, fructose in blood & urine
essential fructosuria
deficiency of aldolase B, autosomal recessive
fructose-1-phosphate accumulates causing decr in avail phosphate
sympt present with fruit, juice, honey consumption
fructose intolerance
accumulation of galacitol
autosomal recessive
infantile cataracts, failure to track objects
galactokinase deficiency
accumulation of galactitol and other toxic substances
autosomal recessive
FTT, jaundice, hepatomegaly, infantile cataracts, intellect disability, E. coli sepsis in neonates
classic galactosemia
what enzyme converts glucose to sorbitol and galactose to galactitol
aldose reductase
what tissues have both aldose reductase & sorbitol dehydrogenase
liver, ovaries, seminal vesicles
which tissues have only aldose reductase
schwann cells, retina, kidneys, lens
methionine, valine, histidine
glucogenic essential a.a.
isoleucine, phenylalanine, threonine, tryptophan
glucogenic/ketogenic essential a.a.
leucine, lysine
ketogenic essential a.a.
aspartic acid, glutamic acid
acidic a.a. (neg charge at body pH)
arginine, lysine, histidine
basic a.a.
required a.a. during periods of growth
arginine, histidine
a.a. high in histones which bind neg charged DNA
arginine, lysine
tremor (asterixis), slurring of speech, somnolence, vomiting, cerebral edema, blurry vision
ammonia intoxication
excess NH4 depletes what enzyme?
alpha ketoglutarate - leads to inhib of TCA cycle
tx for hyperammonemia
lactulose- acidify GIT & trap NH4
Rifaximin- decr colonic ammoniagenic bacteria
benzoate/phenylbutyrate- bind a.a. and excrete
absence of N-acetylglutamate leads to…
hyperammonemia
it is a cofactor for carbamoyl phosphate synthetase I
neonate poor resp & body temp regulation, poor feeding, develop delay, intellect disability
N-acetylglutamate deficiency
most common urea cycle disorder, x linked recessive, interferes w/ body ability to eliminate ammonia
evident in 1st days of life
excess carbamoyl phosphate is converted to orotic acid
ornithine transcarbamylase deficiency
intellectual disability, musty body odor, growth retardation, seizures, fair skin, eczema
phenylketonuria (deficient phenylalanine hydroxylase)
autosomal recessive blocked degradation of branched a.a. (isoleucine, leucine, valine) d/t low alpha ketoacid dehydrogenase
maple syrup urine disease
congenital deficiency of homogentisate oxidase in degradative pathway of tyrosine to fumarate creating pigment forming homogenistic acid accumulates in tissue
autosomal recessive
brown sclera and CT, black urine in air, arthralgias
alkaptonuria (ochronosis)
high homocysteine in urine, intellect disability, osteoporosis, marfanoid habitus, kyphosis, lens subluxation, thrombosis, atherosclerosis
autosomal recessive
cystathionine synthase deficiency
decreased affinity of cystathionine synthase for pyridoxal phosphate
homocysteine methyltransferase deficiency
hereditary defect of renal PCT and intestinal a.a. transporter that prevents reabsorpt of cysteine, ornithine, lysine, arginine
autosomal recessive
cystinuria
severe fasting hypoglycemia, high glycogen in liver, high lactate in blood, high TG’s, high uric acid, hepatomegaly
autosomal recessive deficient glucose 6 phosphatase
Von Gierke disease (type I)
cardiomegaly, hypertrophic cardiomyopathy, exercise intolerance, systemic findings lead to early death
autsomal recessive deficient lysosomal alpha 1,4 glucosidase
pompe disease (type II)
milder form of type I glycogen storage disease with normal blood lactate level
autosomal recessive deficient debranching enzyme (alpha 1,6 glucosidase)
Cori disease (type III)
high glycogen in muscle but muscle can’t break it down - painful muscle cramps, myoglobinuria (red urine), arrhythmia
autosomal recessive deficient skel muscle glycogen phosphorylase (myophosphorylase)
McArdle disease (type V)
periph neuropathy, angiokeratomas, CV/renal disease
X linked recessive deficient alpha galactosidase A
Fabry disease
most common lysosomal storage disease
hepatosplenomegaly, pancytopenia, osteoporosis, aseptic necrosis of femur, bone crises, lipid laden macrophages
autosomal recessive deficient glucocerebrosidase
Gaucher disease
progressive neurodegen, hepatosplenomegaly, foam cells, cherry red spot on macula
autosomal recessive deficient sphingomyelinase
Niemann-Pick disease
progressive neurodegen, developemental delay, cherry red spot on macula, lysosomes with onion skin
autosomal recessive deficient hexosaminidase A
Tay Sachs
periph neuropathy, develop delay, optic atrophy, globoid cells
autosomal recessive deficient galactocerebrosidase
Krabbe disease
central + periph demyelination, ataxia, dementia
autosomal recessive deficient arylsulfatase A
metachromatic leukodystrophy
develop delay, gargoylism, airway obstruction, corneal clouding, hepatosplenomegaly
autosomal recessive deficient alpha L iduronidase
Hurler syndrome
mild Hurler + aggression and no corneal clouding
X linked recessive deficient iduronate sulfatase
Hunter syndrome
increased incidence of what lysosomal storage diseases in ashkenazi jews?
Tay sachs, Niemann pick, Gaucher
inherited defect in transport of LCFAs into mitochondria causing toxic accumulation
weakness, hypotonia, hypoketotic hypoglycemia
systemic 1’ carnitine deficiency
autosomal recessive disorder of FA oxidation
accumulation of 8-10C fatty acyl carnitines in blood
hypoketotic hypoglycemia
vomiting, lethargy, sz, coma, liver dysfunction
medium chain acyl-CoA dehydrogenase deficiency
degrades dietary TG’s in small intestine
pancreatic lipase
degrades circulating TG’s in chylomicrons and VLDLs
found on vascular endothelial surface
lipoprotein lipase
degrades TG’s remaining in IDL
hepatic TG lipase
degrades TG’s stored in adipocytes
hormone sensitive lipase
catalyzes esterification of cholesterol
LCAT
mediates transfer of cholesterol esters to other lipoprotein particles
Cholesterol ester transfer protein CETP
mediates remnant uptake
apoE
activates LCAT
apoA-I
lipoprotein lipase cofactor
apoC-II
mediates chylomicron secretion
apoB-48
binds LDL receptor
apoB-100
transports cholest from liver to tissues
LDL
transports cholest from periphery to liver
HDL
delivers dietary TG’s to peripheral tissue, delivers cholest to liver in form of chylomicron remnants (depleted of TGs)
secreted by intestinal epithel cells
chylomicrons
delivers hepatic TG’s to peripheral tissue
secreted by liver
VLDL
formed in degradation of VLDL
delivers TGs and cholest to liver
IDL
delivers hepatic cholest to peripheral tissues
formed by hepatic lipase modification of IDL in peripheral tissue
taken up by target cells via endocytosis
LDL
mediates reverse cholest transport from periph to liver
repository for apoC & E (needed for chylomicron and VLDL metabolism)
secreted from liver and intestine
alcohol increases its synthesis
HDL
autosomal recessive lipoprotein lipase deficiency or altered apoC-II
pancreatitis, hepatosplenomegaly, xanthomas, no incr risk for atherosclerosis
familial dyslipidemia I- hyperchylomicronemia
autosomal dominant absent/defective LDL receptors
accelerated atherosclerosis, xanthomas, corneal arcus
familial dyslipidemia II- familial hypercholesterolemia
autosomal dominant hepatic overproduction of VLDL
can cause acute pancreatitis
familial dyslipidemia III- hypertriglyceridemia
