Metabolism High Yield Flashcards
Where does beta oxidation occur?
mitochondira
Where does glycolysis occur?
cytoplasm
Where does HMP shunt occur?
cytoplasm
Where does acetyl-CoA production occur?
Mitochondria
Where does Heme synthesis occur?
Both mitochondria and cytoplasm
Where does urea cycle occur?
mitochondria and cytoplasm
Where does TCA cycle occur?
Mitcochondria
What type of enzyme adds inorganic phosphate onto substrate with NO use of ATP?
Phosphorylase
What type of enzyme calalyzes oxidation reduction reactions?
dehydrogenase
What type of enzyme transfers CO2 groups with the help of biotin?
Carboxylase
What enzyme relocates a functional group within a molecule?
Mutase
What is the rate determining enzyme of glycolysis?
PFK1
How does F26BP alter activity of glycolysis?
increased activity of PFK1
How does citrate alter the activity of glycolysis?
increased activity of citrate
What is the rate determining enzyme of gluconeogenesis?
F16BPase
What upregulates F16BPase? What downregulates it?/
Upregulate? ATP and acetyl coA
Downregulate- AMP, F26BP
What is the rate determining enzyme of TCA cycle?
Isocitrate dehydrogenase
What inhibits isocitrate dehydrogenase?
NADH and ATP
What is the rate determining enzyme of glycogenesis?
glycogen synthase
What is the rate determining enzyme of glycogenolysis?
glycogen phosphorylase
What is the rate determining enzyme of HMP shunt?
G6PD
What enhances activity of G6PD?
NADP+
What decreases activity of G6PD?
NADPH
What is the rate determining enzyme of de novo pyrimidine synthesis?
Carbamoyl phosphate synthetase II
What is the rate determining enzyme of de novo purine synthesis?
PRPP aminotransferase
What downregulates PRPP aminotransferase activity?
AMP IMP, GMP
What is the rate determining enzyme of urea cycle?
carbamoyl phosphate synthetase I
What is the rate determining enzyme of fatty acid synthesis?
acetyl coA carboxylase
What is the rate determining enzyme of fatty acid oxidation?
Carnitine acyltransferase I
What downregulates the activity of carnitine aceyltransferase I?
malonyl- CoA
What is the rate determining enzyme of ketogenesis?
HMG- CoA synthase
What is the rate determining enzyme of cholesterol synthesis?
HMG- CoA reductase
What type of processes is NAD+ used in?
CATABOLIC
What type of processes is NADPH used in?
Anabolic processes
What pathway produces NADPH?
HMP shunt
Where is glukokinase found?
LIVER
Where is hexokinase found?
most tissues except the liver and beta pancreatic cells
Which has a lower Km… hexokinase or glucokinase?
Hexokinase
Which has a higher Vmax…hexokinase or glucokinase?
Glucokinase
Which is inducable via insulin…hexokinase or glucokinase?
glucokinase
Which is inhibited by G6P…hexokinase or glucokinase?
Hexokinase
Which steps of glycolysis produces ATP?
Phosphogylcerte kinase
Pyruvate kinase
What inhibits pyruvate kinase?
Alanine and ATP
What enzyme is active in the fasting state…FBPase2 or PFK-2?
FBPase2–> converts F26BP back to F6P
What enzyme is active in the fed state… FBPase2 or PFK-2?
PFK-2–> converts F6P to F26BP
What are the 5 cofactors needed for pyruvate dehydrogenase complex?
B1, B2 B3, B5, Lipoic acid
What inhibits lipoic acid?
Arsenic
What is the treatment for pyruvate dehydrogenase complex deficiency?
increase intake of ketogenic nutrients (high fat or increased lysine and leucine)
What are the symptoms of pyruvate dehydrogenase complex deficiency?
Lactic acidosis, neuro defects and increased serum alanine
What 4 molecules does pyruvate lead to?
1- Alanine
2- Oxaloacetate
3- Acyl- CoA
4- Lactate
How many molecules of NADH, FADH2, CO2 and GTP produces per acetyl CoA?
NADH- 3
FADH2- 1
CO2- 2
GTP- 1
Order of molecules in the TCA cycle?
Citrate Isocitrate alpha- Ketogluteate Succinyl- CoA Succinate Fumarate Malate Oxaloacetate
What complex in the ETC does FAD2 transfter electrons to?
Complex II (lower energy than NADH transfer (complex I)
What does rotenone block?
complex I
What does cyanide block?
Complex IV
What does antimycin A block?
Complex III
What does CO block?
complex IV
What does oligomycin blocl?
complex V
Name 2 uncoupling agents?
2,4- dinitrophenol
Aspirin
Name the enzyme:
Pyruvate–> OAA
Pyruvate carboxylase
Name the enzyme:
OAA–> PEP
Phosphoenolpyruvvate carboxykinase
Name the enzyme:
F16BP–> F6P
F16BPase
What gluconeogenesis enzyme do muscles lack?
G6Pase
Deficiency in enzymes of gluconeogenesis results in…
hypoglycemia
Does HMP shunt produce ATP?
NO!!!
Which phase of the HMP shunt produces NADPH?
Oxidtive/ irreversible
Aside from producing NADPH, what are the other benefit if the HMP shunt?
Produces glycolytic intermediates and ribose for nucleotide synthesis
What enzyme is defieicny in essential fructosuria?
Fructokinase
AR
What enzyme is deficienct in fructose intolerance?
Aldolase B
AR
What accumulates in fructose intolerance?
F1P
this leads to decrease in phosphate (inhibition of glycogenolysis and gluconeogenesis)
What is the treatment for fructose intolerance?
Decrease intake fructose and sucrose
What enzyme is deficient in galactose deficiency?
Galactokinase (cannot convert galactose to Galactose 1 Phosphate)
What molecule increases in galactokinase deficiency?
Galactitol–> leads to infantile cataracts
What enzyme is deficient in classic galactosemia?
Galactose 1 phosphate uridyltransferase
What is the treatment for classic galactosemia?
exclude galactose and lactose from diet
What is sorbitol metabolized to?
Fructose
What enzyme produces sorbitol from glucose?
Aldolase reductase
What results from increased sorbitol wthin cells?
Osmotic damage (cataracts, retinopathy, peripheral neuropathy)
What is lactose metabolized into?
Glucose + galactose
Name the essential gluconeogenic amino acids?
Methionine
Valine
Histidine
What are the ketogenic essential amino acids?
Leucine
Lysine
What are the essential amino acids that are both ketogenic and glucogenic?
Isoleucine
Phenylalanine
Threonine
Tryptophan
Which amino acids are negatively charged at body pH?
Aspartic acid
Glutamic acid
Which amino acids are positively charged at the body pH?
Arginine
Lysine
Histidine
In the transport of ammonia…amino acids transfer their NH3 to what compound?
Glutamate which then transfers it to alanine
What is the cahill cycle?
Alaine (muscle)–> alanine (liver)–> pyruvate–> glucose (liver)–> glucose (muscle)–> pyruvate–> alanine (muscle)
What is the cori cycle?
Lactate (muscle–> lactate (liver)–> pyruvate–> glucose (liver)–> glucose (muscle)–> pyruvate –> lactate (muscle)
What is the most common deficiency of the urea cycle?
Ornithine transcarbamylase
NAG synthase deficiency affects which enzyme in the urea cycle?
Carbamoyl phosphate synthas I
Where are the enzymes carbamoyl phosphate synthase and ornithine transcarbamylase located?
Mitochondria
What amino acid is the backbone of urea?
Aspartate
What is the treatment for hyperammonemia?
Lactulose (ascidify the GI and trap NH4 for excretion
Tyrosine is a derivative of which amino acid?
phenylalanine
Niacin is a derivative of which amino acid?
Tryptophan
Serotonin is a derivative in which amino acid?
Tryptophan
Prophyrin and heme is a derivative of which amino acid?
Glycine
Glutathione is a derivative of which amino acids?
glutamate
Urea is a derivative of which amino acid?
arginine
NO is a derivative of which aminoa cid?
argining
NE/ DA/ Epi are derivatives of which amino acids?
Phenylalanine
Cofactor for dopamine–> NE?
vit C
Cofactor for NE–> Epi?
SAM
What phenylalanine derivative is melatin made from? What enzyme is responsible?
Made from DOPA
Tryosinase!
What is deficient in malignant PKU?
tetrahydrobiopterin cofactor
“musty body odor”
PKU
What enzyme is deficient in maple syrup urine disease?
alpha ketoacid dehydrogenase
“burnt sugar smelling urine”
Maple syrup urine disease
What amino acids are to be avoided in maple syrup urine disease?
isoleucine
Leucine
Valine
(branched amino acids)
“black urine when exposed to air”
Alkaptonuria
What is deficient in alkaptonuria?
Homogentisate oxidase
What pathway is defective in alkaptonura?
Tyrosine–> fumarate
What are the symptoms of homocystinuria?
1- intellectual disability
2- marfanoid habitus
3- lens sublixation
4- atherosclerosis
What amino acids cannot be reabsorbed in the PCT in cystinuria?
COLA
Cystine
Onithine
Lysine
Arginine
What type of receptor is the insulin receptor?
tyrosine kinase
What type of receptor is glucagon receptor?
increased cAMP–> increased PKA–> increased glycogen phosphoryalase kinase
What organ maintains blood sugar at appropriate levels?
Hepatocytes
What enzyme breaks alpha 1,4 linkages?
glycogen phosphorylase
What are the two debranching enzyme?
4alpha D glucanotransferase
alpha-1,6- glucosidase
Is glycogen phosphorylase active when it is dephosphorylated or phosphorylated?
Phosphorylated
What enzyme deficiency leads to severe fasting hypoglycemia, increased glycogen in liver, increased blood lactate, increased triglycerides, increased uric acid and hepatomegaly?
Glucose 6 phosphatase
von gierke disease
What enzyme deficeicny leads to cardiomegaly, hypertrophic cardiomyopathy, exercise intolerance, systemic findings leading to early death?
Lysosomal alpha 1,4 glucosidase (acid maltase)
Pompe disease (type II)
What enzyme deficiency leads to is a milder form of type I glycogen storage disease with normal blood lactate levels?
Debranching enzyme (alpha 1,6 glucosidase
Cori Disease (type III)
What enzyme deficiency leads to increased glycogen storave in muscles but muscles cannot break it down leading to painful cramps, red urine after strenuous exercise?
Skeletal muscle glycogen phosphorylase (myophosphorylase)
McArdle disease (Type V)
How is McArdle disease treated?
B6
Deficient enzyme in fabry disease?
alpha- galactosidase A
Deficient enzyme in gaucher disease?
Glucocerebrosidase
Deficient enzyme in Niemann pick disease?
Shingomyelinase
Deficient enzyme in Tay sachs disease?
Heosaminidase A
Deficient enzyme in Krabbe disease?
Galactoerebrosidase
What enzyme is deficiient in Metachromatic leukodystrophy?
Arylsulfatase A
Deficient enzyme in Hurler syndroe?
alpha- L idurinidase
What is the deficient enzyme in Hunter syndrome?
Iduronate sulfatase
Name the lysosomal storage disease:
progressive neurodegeneration, foam cells, “cherry red” macula, hepatosplenomegaly
Neiman Pick
What builds up in nieman pick?
Sphingomyelin
Name the lysosomal storage disease:
central and peripheral demyelination with ataxia and dementia
Metachromatic leukodystrophy
What builds up in metachromatic leukodystrophy?
cerebroside sulfate
Name the lysosomal storage disease:
peripheral neuropathy of hands/ feet, angiokeratomas, CV and renal disease
Fabry disease
What builds up in fabry disease?
ceramide trihexoside
Name the lysosomal storage disease:
progressive neurodegeneration, delayed development, cherry red macula, lysosomes with onion skin
Tay sachs disease
What builds up in Tay sachs?
GM2 ganglioside
Name the lysosomal storage disease:
hepatosplenimegaly, pancytopenia, osteoporiss, necrosis of femus, lipid laden macrophages”
gaucher disease
What builds up in gaucher disease?
glucocerebroside
Name the lysosomal storage disease:
“peripheral neuropathy, developmental delay, optic atrophy, globoid cells
Krabbe disease
What builds up in krabbe disease?
Galactocerbroside
Name the lysosomal storage disease:
mild developmental delay, mild airway obstruction, mild hepatosplenomegaly, agressive behavior
hunter syndrome
Name the lysosomal storage disease:
developpmental delay, gargoylism, airway obstruction, corneal clouding, hepatosplenomegaly
Hurler syndrome
Inherited defect in transport of LCFAs in the mitochondria?
Systemic primary carnitine deficiency
Fatty acid synthesis requires the transport of _____ from the mitochondria to the cytosol.
Citrate
“inability to breakdown fatty acids into acetyl coA leading to accummulation of 8- 10 carbon fatty acyl in the blood”
Medium chain acyl CoA dehydrogenase deficiency
What leads to the production of ketone bodies?
Excess acetyl- CoA (glucose and FFA are shunted to ketone formation)
What maintains blood glucose levels in fasting states between meals?
hepatic glycogenolysis (major)
What maintains blood glucose levels during starvation between 1-3 days?
Hepatic glycogenolysis, adipose release of FFA, muscle and liver, hepatic gluconeogenesis from peripheral lactate and alanine
How long does it take for glycogen to be depleted?
1 day
What maintains blood glucose levels during starvation after day 3?
adipose stores (ketone bodies from acyl coA)
then after adipose stores are depleted protein degredation accelerates
What induces the enzyme HMG- CoA reductase?
insulin
What esterifies plasma cholesterol?
LCAT
What cells release VLDL?
Hepatocytes
What converts chylomiccrons to chylomicron remnants?
LPL
What converts VLDL–> IDL?
LPL
What converts IDL–> LDL?
Hepatic TG lipase
What cells release HDL?
Liver and intestine
What enzyme makes nascent HCL mature?
LCAT
What is the function of Mature HDL?
Transfer of cholesterol esers to VLDL, IDL, and LDL via CETP (cholesterol ester transfer protein)
What is the function of ApoE?
mediates remnant uptake
What molecules have ApoE?
Chylomicron Chylomicron remnant VLDL IDL HDL
What is the function of Apo A-I?
Activates LCAT
What molecules have Apo A-I?
Chylomicron
HCL
What is the function of Apo C-II?
LPL cofactor
What molecules have Apo C-II?
Chylomicron
VLDL
HDL
What is the function of Apo B-48?
Mediates chylomicron secretion
What molecules have Apo B-48?
Chylomicron
Chylomicron remnant
What is the function of Apo B-100?
Binds LDL receptor
What molecules have Apo B-100?
VLDL
IDL
LDL
Which molecule acts as a reserviour of Apo E and C-II?
HDL
What secretes HDL?
liver and intestine
Which familiar hyperlipidemia has absent LPL or altered Apo C-II?
Type I
Which familiar hyperlipidemia has absent or defective LDL receptor?
Type II
Which familial hyperlipidemia has hepatic overproduction of VLDL?
Type IV
