Term
| glucose transporters on most tissues, basal glucose uptake |
|
Definition
|
|
Term
| glucose transporters on liver, pancreatic B cells |
|
Definition
|
|
Term
| glucose transporters on skeletal muscle and adipose tissue, insulin-dependent |
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
hexokinase or glucokinase
hexokinase - all tissues, small Km
glucokinase - only liver, pancreatic beta cell, large Km |
|
|
Term
|
Definition
| fructose 2,6 bis-P, product of PFK-2 on fructose 6P |
|
|
Term
|
Definition
|
|
Term
second most common genetic deficiency causing hemolytic anemia
2 distinguishing features? |
|
Definition
pyruvate kinase deficiency
-no Heinz bodies
-increased 2,3 DPG (lower than normal oxygen affinity) |
|
|
Term
| pyruvate + NADH -> lactate + NAD |
|
Definition
lactate dehydrogenase
important in anaerobic glycolysis to reoxidize NADH |
|
|
Term
| pyruvate + CoA + NAD -> acetyl CoA + CO2+ NADH |
|
Definition
pyruvate dehydrogenase
requires cofactors (thiamine, lipoic acid, CoA, FAD, NAD) |
|
|
Term
| cause of neonatal type I diabetes |
|
Definition
glucokinase deficiency in newborn
pancreatic B cells cannot detect glucose and do not secrete insulin |
|
|
Term
| glycolysis intermediate used in trigylceride synthesis |
|
Definition
| DHAP -> glycerol 3P -> triglyceride backbone |
|
|
Term
|
Definition
galactokinase deficiency
sx: cataracts early in life, galactitol trapped in lens causes swelling and cataracts |
|
|
Term
|
Definition
galactose 1P uridyltransferase deficiency
more severe because galactose 1P accumulates in liver, brain, etc
sx: cataracts early in life
vomiting, diarrhea following lactose ingestion
lethargy
mental retardation
liver damage, hyperbilirubinemia |
|
|
Term
|
Definition
fructokinase deficiency
benign |
|
|
Term
|
Definition
aldolase B deficiency, autosomal recessive
sx: lethargy, vomiting
liver damage, hyperbilirubinemia
hypoglycemia, hyperuricemia
kidney disease |
|
|
Term
|
Definition
isocitrate dehydrogenase
activated by ADP
inhibited by NADH, ATP
no hormonal control |
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
oxidize acetyl CoA -> CO2
no net production of TCA intermediates! |
|
|
Term
| thiamine, lipoic acid are cofactors for these enzymes (3) |
|
Definition
-pyruvate dehydrogenase (glycolysis)
-a-ketoglutarate dehydrogenase (TCA)
-transketolase (HMP shunt) |
|
|
Term
TCA intermediates involved in other pathways:
-gluconeogenesis
-fatty acid synthesis
-heme synthesis |
|
Definition
TCA intermediates involved in other pathways:
-malate
-citrate
-succinyl CoA |
|
|
Term
| location: electron transport chain |
|
Definition
inner mitochondrial membrane
protons pumped into intermembrane space |
|
|
Term
|
Definition
CN inhibits electron transport chain
antidote: nitrates to convert hemoglobin to methemoglobin, metHb binds CN avidly |
|
|
Term
| inhibitors of the electron transport chain |
|
Definition
|
|
Term
|
Definition
| glucose 6 phosphate dehydrogenase (G6PD) |
|
|
Term
|
Definition
|
|
Term
|
Definition
produce NADPH from abundant glucose 6 P
produce ribulose 5P for nucleotide synthesis |
|
|
Term
| oxidative, irreversible step in HMP shunt |
|
Definition
glucose 6P -> NADPH and ribulose
enzyme: glucose 6P dehydrogenase |
|
|
Term
| nonoxidative, reversible step in HMP shunt |
|
Definition
ribulose 5P -> ribulose 6P
enzyme: transketolases |
|
|
Term
|
Definition
NADPH oxidase cofactor: PMN bacteria killing
regenerates reduced glutathione: protects against ROS damage |
|
|
Term
|
Definition
glucose 6P dehydrogenase is RDS enzyme in HMP shunt
acute, episodic hemolytic anemia with oxidative stress (overwhelming infxn, fava beans)
x-linked recessive, heterozygote females have malaria advantage |
|
|
Term
| key enzymes in glycogen synthesis |
|
Definition
glycogen synthase (RDS) (a 1,4 bonds)
branching enzyme (a 1,6 bonds) |
|
|
Term
| key enzymes in glycogenolysis |
|
Definition
glycogen phosphorylase (RDS) (a 1,4 bonds)
debranching enzyme (a 1,6 bonds) |
|
|
Term
|
Definition
type I glycogen storage disease
glucose 6 phosphatase deficiency
sx: severe fasting hypoglycemia
high glycogen accumulation in liver leads to hepatomegaly
high blood lactate, hyperuricemia, hyperlipidemia |
|
|
Term
|
Definition
type II glycogen storage disease
more similar to lysosomal storage diseases: inclusion bodies in lysosomes
lysosomal a 1,4 glucosidase deficiency
sx:
glycogen accumulation leads to hepatomegaly, cardiomegaly and muscle weakness
early death without tx
tx: enzyme replacement |
|
|
Term
|
Definition
type III glycogen storage disease
debranching enzyme deficency
sx: milder form of type I - mild hypoglycemia and mild hepatomegaly
normal blood lactate |
|
|
Term
|
Definition
type V glycogen storage disease
muscle glycogen phophorylase deficiency
sx: cramps & weakness with exercise
tx: sucrose load before excercise |
|
|
Term
|
Definition
lactate becomes glucose in liver
cost of 4 ATP per cycle |
|
|
Term
|
Definition
fructose 1,6 bisphosphatase: fructose 1,6 bis-P -> fructose 6P
activated by ATP
inhibited by AMP, fructose 2,6 bis-P |
|
|
Term
|
Definition
pyruvate carboxylase
requires biotin
mitochondrial enzyme |
|
|
Term
|
Definition
PEP carboxykinase
requires GTP
cytoplasmic enzyme
PEPCK expression regulated by cortisol and glucagon |
|
|
Term
| how does acetyl CoA regulate the fate of pyruvate? |
|
Definition
| high acetyl CoA stimulates pyruvate carboxylase (gluconeogenesis) and inhibits pyruvate dehydrogenase. high acetyl CoA occurs during fasting (due to fatty acid oxidation). |
|
|
Term
| how does alcoholism predispose to hypoglycemia? |
|
Definition
| NAD is converted to NADH in alcohol metabolism by alcohol dehydrogenase. high NADH diverts gluconeogenic substrates (pyruvate -> lactate, etc) |
|
|
Term
|
Definition
| inhibits lipoic acid, which is a cofactor for pyruvate dehydrogenase and a-ketogluterate dehydrogenase |
|
|
Term
|
Definition
| acetyl CoA carboxylase: acetyl CoA -> malonyl CoA (eventually forms palmitate) |
|
|
Term
| what is the citrate shuttle? |
|
Definition
| carries acetyl CoA out of the mitochondria to cytoplasm where FA synthesis takes place |
|
|
Term
| sources of glycerol 3P for triglyceride synthesis |
|
Definition
DHAP from glycolysis
Phosphorylation of free glycerol (liver only) |
|
|
Term
|
Definition
triglyceride rich lipoprotein
secreted by intestinal epithelium
delivers dietary TG to periphery
Apo B-48, C and E |
|
|
Term
|
Definition
triglyceride rich lipoprotein
secreted by liver
delivers TG from liver to periphery
Apo B-100, C and E |
|
|
Term
|
Definition
aka VLDL remnant
acquire cholesterol from HDL and become LDL |
|
|
Term
|
Definition
"bad (Lousy) cholesterol"
delivers cholesterol from liver to periphery
Apo B-100 |
|
|
Term
|
Definition
"good (Healthy) cholesterol"
reverse cholesterol transport: delivers cholesterol from periphery to liver
secreted by liver and intestine
donates Apo C and E to chylomicrons and VLDL |
|
|
Term
|
Definition
on chylomicrons, required for secretion from intestinal epithelium
48 => what you ATE |
|
|
Term
|
Definition
1. on VLDL and LDL, required for secretion from liver
2. binds LDL receptor |
|
|
Term
|
Definition
required for remnant uptake by liver
donated to chylomicrons and VLDL by HDL |
|
|
Term
|
Definition
type I familial dyslipidemia
lipoprotein lipase deficiency
high TG in the form of chylomicrons
sx: pancreatitis, hepatosplenomegaly, eruptive xanthomas, *no* increased risk of atheroscelrosis |
|
|
Term
| familial hypercholesterolemia |
|
Definition
type IIa familial dyslipidemia
LD receptor deficiency
autosomal dominant
high cholesterol in the form of LDL
sx: accelerated atherosclerosis, tendon xanthomas, corneal arcus |
|
|
Term
|
Definition
type IV familial dyslipidemia
high TG in the form of VLDL
hepatic overproduction of VLDL
sx: pancreatitis |
|
|
Term
|
Definition
apo B-100 and B-48 deficiency
autosomal recessive
sx in the first few months of life:
failure to thrive, steatorrhea, acanthocytosis, ataxia, night blindness |
|
|
Term
| RDS cholesterol synthesis |
|
Definition
HMG CoA reductase: HMG CoA -> mevalonate
inhibited by statins |
|
|
Term
| lipoprotein lipase vs hormone sensitive lipase |
|
Definition
LPL acts on chylomicrons and VLDL to release FA in adipose tissue. stimulated by insulin (fed state).
HSL acts on adipose tissue to release FA for B oxidation. inhibited by insulin, stimulated by epi and cortisol (fasting state). |
|
|
Term
| Lecithin cholesterol acyltransferase (LCAT) |
|
Definition
| enables reverse trasnport of cholesterol from periphery to liver: forms cholesterol esters, which are soluble in HDL core |
|
|
Term
| cholesterol ester transfer protein (CETP) |
|
Definition
| mediates transfer of cholesterol pesters from HDL to IDL (forming LDL). |
|
|
Term
|
Definition
linolenic acid
linoleic acid |
|
|
Term
| how do statins cause rhabdomyolysis? |
|
Definition
one of the cholesterol synthesis intermediates can be used to synthesize coenzyme Q for the ETC.
less CoQ -> impaired mito function and ATP synthesis -> muscle cell damage |
|
|
Term
|
Definition
lysosomal storage disease, AR
deficient enzyme: hexosaminidase A
accumulated substrate: ganglioside GM2
sx: death by 2yo, progressive neurodegeneration, cherry-red spot on macula, *NO* hepatosplenomegaly |
|
|
Term
|
Definition
lysosomal storage disease, AR
deficient enzyme: B-glucocerebrosidase
accumulated substrate: glucoserebroside
sx: *crumpled paper* macrophages, avascular necrosis of femur, hepatosplenomegaly |
|
|
Term
|
Definition
lysosomal storage disease, AR
deficient enzyme: sphingomyelinase
accumulated substrate: sphingomyelin
sx: progressive neurodegeneration, hepatosplenomegaly, cherry-red spot on macula, foamy macrophages |
|
|
Term
|
Definition
carbamoyl phosphate synthetase I:
NH4+ + CO2 -> caramoyl phosphate
cost: 2ATP |
|
|
Term
|
Definition
| convert excess nitrogen (NH4+) to urea for excretion by kidneys |
|
|
Term
|
Definition
| mitochondria and cytoplasm of liver |
|
|
Term
| lab values that suggest urea cycle defect |
|
Definition
high ammonium
high glutamine
low urea (low BUN) |
|
|
Term
| most common urea cycle disorder |
|
Definition
| ornithine transcarbamoylase deficiency |
|
|
Term
| carbamoyl phosphate synthetase deficiency vs. ornithine transcarbamoylase deficiency |
|
Definition
uracil and orotic acid elevated in ornithine transcarbamoylase deficiency
OTC deficiency is x-linked recessive, CPS deficiency is AR
both are mitochondrial enzymes in urea cycle,
cause high ammonium, high glutamine, low urea,
sx: cerebral edema, lethargy, seizures, coma, death in neonate 24 hours after birth |
|
|
Term
|
Definition
leucine, lysine
can make ketone bodies in severe fasting |
|
|
Term
| ketogenic & glucogenic AA |
|
Definition
isoleucine, threonine, tyrosine, tryptophan, phenylalanine
feed gluconeogenesis in severe fasting |
|
|
Term
|
Definition
phenylalanie hydrozylase deficiency
autosomal recessive
sx: MR, growth retardation, seizures, *musty* body odor
tx: limit dietary phenylalanine, tyrosine becomes essential, monitor in pregnancy
*Nutrasweet (aspartame) contains phenylalanine |
|
|
Term
|
Definition
homogentisic acid oxidase deficiency
autosomal recessive
sx: ochronosis, arthritis
tx: *symptomatic* only, benign disease |
|
|
Term
Homocystinuria
*increased risk of?* |
|
Definition
cystathionine synthase deficiency or
homocysteine methyltransferease deficiency
autosomal recessive
sx: mental retardation, osteoporosis, tall stature (Marfanoid), kyphosis, lens subluxation, atherosclerosis (*stroke and MI*)
tx: for cystathionine synthase deficiency, use homocysteine methyltransferease to degrade homocysteine to methionine: decrease methionine and increase cysteine + B12 intake
*cysteine becomes essential |
|
|
Term
|
Definition
renal proximal tubular AA transporter defect
cystine = 2 cysteines linked by disulfide bond
sx: cystine kidney stones
tx: *acetazolamide* to alkalinize the urine |
|
|
Term
| Maple syrup urine disease |
|
Definition
branched chain ketoacid dehydrogenase deficiency
sx: days old infant becomes lethargic, CNS defects/MR/death if untreated
tx: limit dietary isoleucine, leucine, valine (I Love Vermont) |
|
|
Term
|
Definition
renal neutral AA transporter defect, *tryptophan* excretion in urine
sx: pellagra (niacin is derived from tryptophan) |
|
|
Term
|
Definition
delta-aminolevulinate synthetase:
glycine + succinyl CoA -> delta-aminolevulinic acid
requires *vitamin B6*
inhibited by heme |
|
|
Term
| Acute intermittent porphyria |
|
Definition
urobilinogen-1 synthase deficiency (heme synthesis)
autosomal dominant but late onset and variable expression
pain in abdomen
polyneuropathy
psych*
pink urine
precipitated by drugs (*barbituates*, OCP, sulfa drugs) |
|
|
Term
|
Definition
defect in other heme synthesis enzymes
cutaneous: photosensitivity, blistering |
|
|
Term
|
Definition
inhibits heme synthesis: ALA dehydrase, ferrochelatase
sx: microcytosis, basophilic stipling, ringed sideroblasts, lead lines in gums and epiphyses |
|
|
Term
| Heme metabolism pathway: heme -> |
|
Definition
biliverdin
bilirubin
conjugated bilirubin (in liver)
urobilinogen (in intestine, by bacteria)
stercobilin (feces) or urobilin (urine) |
|
|
Term
|
Definition
| UDP glucuronyl transferase deficiency |
|
|
Term
|
Definition
| UDP glucuronyl transferase deficiency |
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
| important purine and pyrimidine precursors |
|
Definition
purine: IMP
pyrimidine: orotic acid, UMP |
|
|
Term
| RDS de novo purine synthesis |
|
Definition
| glutamine PRPP amidotransferase |
|
|
Term
| RDS de novo pyrimidine synthesis |
|
Definition
carbamoyl phosphate synthetase II:
glutamine + CO2 -> carbamoyl phosphate
*note: carbamoyl phosphate also a urea cycle intermidate |
|
|
Term
| Adenosine deaminase deficiency |
|
Definition
purine salvage deficiency, major cause of SCID
high levels of dATP inhibit synthesis of other DNA precursors -> B and T cell dysfunction |
|
|
Term
|
Definition
absent HGPRT, defective purine salvage
X-linked recessive
sx: unrecovered purines are degraded to uric acid -> hyperuricemia, gout, *self-mutilation*, aggression |
|
|
Term
|
Definition
defect in de novo pyrimidine synthesis: cannot convert orotic acid to UMP
autosomal recessive
sx: days old infant with orotic acid in urine (but not hyperammonemia as in OTC deficiency - urea cycle defect), megaloblastic anemia that does not resolve with B12 or folate, failure to thrive
tx: oral uridine (salvaged to UMP) |
|
|
Term
| antineoplastic drugs that inhibit enzymes in pyrimidine de novo synthesis (3) |
|
Definition
hydroxyurea - ribonucleotide reductase
5-fluorouracil - thymidylate synthase
methotrexate - dihydrofolate reductase |
|
|
