Metabolism High Yield Flashcards
How does fomepizole work?
This inhibits alcohol dehydrogenase and is an antidote for methanol or ethylene glycol poisoning.
How does Disulfram work?
Inhibits acetalaldehyde dehydrogenase causin acetaldehyde to accumulate and cause hangover symptoms.
What is the rate limiting reagent in ethanol metabolism?
NAD+
What does alcohol dehydrogenase do in ethanol metabolism?
Utilizes NAD+ to oxidize alcohol to acetaldehyde.
Acetaldehyde dehydrogenase then uses another NAD+ to form acetate in the mitochondria.
Where in the cell does glycolysis occur?
Cytoplasm
Glycolysis fatty acid synthesis and HMP shunt occurs in the cytoplasm as well.
Same with cholesterol
which three processes occur in both the cytoplasm and the mitochondria?
Heme synthesis
Urea cycle
Gluconeogenesis
“HUG’s take two”
Phosphofructokinase-1 is the rate limiting enzyme for…
Glycolysis
Fructose-1,6-bisphosphatase is the rate limiting enzyme for…
Gluconeogensesis
Isocitrate dehydrogenase is the rate limiting enzyme for…
TCA cycle
Glycogen synthase is the rate limiting enzyme for…
glycogensesis
Glycogen phosphorylase is the rate limiting enzyme for…
Glycogenolysis
Glucose-6-phosphate dehydrogenase (G6PD) is the rate limiting enzyme for…
HMP Shunt
For NADP+ and NADPH
Carbamoyl phosphate synthetase II is the rate limiting enzyme for…
De novo pyrimidine synthesis
Glutamine-phosphoribosylpyrophosphate amidotransferase is the rate limiting enzyme for…
De novo purine synthesis.
Carbamoyl phosphate synthetase I is the rate limiting enzyme for…
Urea cycle
Acetyl-CoA carboxylase is the rate limiting enzyme for…
Fatty acid synthesis
Carnitine acyltransferase I is the rate limiting enzyme for…
Fatty acid oxidation
HMG-CoA synthase is the rate limiting enzyme for…
Ketogenesis
HMG-CoA reductase is the rate limiting enzyme for…
Cholesterol synthesis
How much ATP is formed with aerobic vs anaerobic metabolism?
32 net ATP in aerobic and 2 ATP via anerobic.
Describe the diference between hexokinase and glucokinase.
Hexokinase is within most tissue except for the liver and beta pancreatic cells. It has a low affinity and low Vmax and is constantly on (not induced by insulin) this allows fo the common uptake of glucose in the body.
glucokinase however is found in the liver and Beta cells of the pancreas. It has very high affinity and Vmax and is turned on by insulin to greatly drive sugar into the liver for storage.
Which two amino acids are purely ketogenic?
Lysine and Lucine
What is the responsibility of the pyruvate dehydrogenase complex
Converts pyruvate into acetyl CoA effectively linking glycolysis into the TCA.
What is the purpose of converting glucose to alanine?
Alanine transports (ALT) glucose from the skeletal muscle to the liver. Works through vitamin B6 (pyridoxine)
What is the pyhrpose of formin oxaloacetate via pyruvate carboxylase?
Oxaloacetate can replenish the TCA cycle or be used in gluconeogenesis.
How many ATP are produced per aceyl-CoA?
10 ATP
Each glucose molecule yields 2 Acetyl-CoA so total of 20 ATP.
What is the begining and end products of the TCA?
Begins with Acetyl-CoA being converted to Citrate by ATP.
Ends with Malate reducing NAD+ to form Oxaloacetate.
At which step of the TCA is FADH2 formed?
Succinate converted to fumerate.
At which step of the TCA is GTP formed?
Succinyl-CoA converted to Succinate.
At which step of the TCA is NADH formed?
Isocitrate to alpha ketogluterate
Alpha ketogluterate to succinyl CoA
Malate to oxaloacetate.
Which substances help to create the electron transport chain and aid in oxidative phosphorylation/
NADH (complex 1) and FADH2 (complex 2) both supply the electrons needed and enter via the malate aspartate or glycerol-3 phosphate shuttle system.
Which electron transport complex is effected by cyanide?
Complex IV2
Which type of fatty acid chains can produce new glucose?
Only odd chain!
Even chains cannot produce new glucose since they yield only acetyl-CoA equivalents.
What role does NADPH have?
NADPH serves to….
Glutathione in detox of RBC
Fatty acid and cholesterol biosynthesis.
How is NADPH made?
Glucose 6- dehydrogenase forms it!
It is an irreversible oxidative step that occurs when there is excess Glucose 6-Phosphate and high levels of NADP+
What happens when there is a NADPH deficiency in RBC?
Hmolytic anemia due to poor defence against oxidizing agents such as fava beans, sulfonamides, primaquine, and antituberculosis drugs.
What is the difference between heinz bodies and bite cells?
Heinz bodies are RBC that have been denatured due to oxidative stress.
Bite cells are defective RBC that have had a bite taken out of them in the splene by macrophages.
Both of these conditions are seen when there is a glutathione/NADPH deficiency which is an X-linked recessive disorder commonly seen in african american males.
Essential fructosuria vs fructose intolerance
Essential fructosuria involves a defect in fructokinase.
Fructuse is trapped in the blood and urine but will not get into the liver.
Fructose intolerace: Defect in aldolase B (Allows fructose to be broken down for glycolysis) thus fructose 1 phosphate accumulates causing a decrease in the availability of phosphate inhibiting glycogenolysis and gluconeogenesis. Will see symptoms after eating fruit, juice or honey.
Fructose is to Aldolase B as Galactose is to…
UridylTransferase (FAB GUT)
Describe sorbitol
An alternative way to trap glucose in the cell.
Utilizes aldose reductase and NADPH to form sorbitol. and then Sorbitol dehydrogenase to form fructose.
If there are excessive ammounts of glucose in the system it can accumulate specifically in the eye.
Schwann cells, the kidney and the retina/lens have aldose reductase only and thus are at increased risk for sorbitol damage.
Which organs are at the most risk for sorbitol damage in hyperglycemic states?
Schwann cells, the kidney, the retina and the lens.
What is the only amino acid type found in human proteins?
Only the L-type!
Ordinarily careless crappers are also frivulous about urination
Explains the steps in the urea cycle.
Ornithine + Carbamoyl phosphate synthetase Citruline Argininosuccinat Arginine + Fumarate Urea
What enters the urea cycle?
Carbamoyl phosphate from CO2 and NH3 in the mitochondria.
Will work with ornithine transcarbamylase and ornithine to form citrilline.
What step of the urea cycle requires ATP?
Aspartate interacting with citruline to form argininosuccinate.
What molecule is needed to interact with arginine to form ornithine?
Arginase takes arginine and forms ornithine by use of water.
Describe the Cori Cycle
This is a cycle of transporting glucose from the muscle to the liver.
It converts lactate into pyruvate into glucose and vice-versa.
What is the Cahill cycle?
The process of transfering glucose from the muscle to the liver using alanine which can be converted back to glucose.
How does hyperammonemia lead to supressed TCA?
Excessive NH4 depletes alpha ketogluterate resulting in an inhibition of the TCA cycle.
Tx with Rifamimin.
Describe ornithine transcarbamylase deficiency
Most common deficiency of the urea cycle.
This is the first enzyme in the cycl and is X-linked recessive disorder.
Excess carbamoyl phosphate is converted to orotic acid.
will have excess orotic acid in the bood!!!!
What amino acid is needed to form serotonin?
Tryptophan can form serotonin and from serotonin melatonin.
What amino acid is needed to form dopamine, NE, and Epi?
Phenylalanine can be formed into tyrosine.
Tyrosine is ultimately needed here.
What A.A is needed to make thyroxine?
tyrosine
What is needed to make melanin?
Dopamine formed from tyrosine.
What vitamin is neded to convert dopamine into NE?
Vitamin C.
How does one end up with Alkaptonuria?
Homogentisate oxidase deficiency shutting down fumarate formation and enterance into the TCA.
Maple syrup urine disease
Blocked degradation of BRANCHED amino acids (isoleucine, leucine, and valine) due to decreased alpha ketoacid dehydrogenase.
Alkaptonuria
Congenital deficiency of homogentisate oxidase in the degradative pathway of tyrosine to fumarate.
Look for dark pigmented skin and black urine when exposed to air.
Cystinuria
Hereditary defect of renal PCT and intestinal amino acid transporter preventing reabsorption of
Cysteine
Ornithine
Lysine
Arginine
“COLA”
Excess cysteine in urine can lad to hexagonal cysteien stones.
treat with alkalinazation and chelatine agents,
What is glucose released as from gylcogen?
Glucose 1-phosphate needs to be transformed into Glucose 6-phosphate before being removed.
4 alpha lucanotrasferase
Debranching enzyme.
Works when there are only 4 glucose molecules left on a glycogen branch and moves 3 molecules of glucose 1 phosphate from the branch to the linkage.
Also cleaves off the last residue to liberate the glucose.
What genetic inheritence do all of the glycogen storage diseases follow?
Autosomal recessive.
What is the only lysosomal storgage disease that is not autsomal recessive?
Fabry’s disease which is X-linked recessive.
Fatty acid synthesis requires transport of …. from the mitochondria to the cytosol.
Requires transport of citrate from the mitochodria to the citrate.
Predominantly in the liver, lactating mammary glands and adipose tissue.
Long chain fatty acid degradation requires …. dependent transport into the mitochondrial matrix.
Requires carnitine dependent transport ito the mitochondrial matrix.
Think, sytrate for Synthesis
Carnitine for Carnage of fatty acids!!!
What does fatty acid get converted into?
Fatty acid is converted into Acyl-CoA
A build up of Acetyl-CoA from excess NADH leads to….
Leads to the buildup of acetyl-CoA shunting glucose and FFA toward the production of ketone bodies.
How many calories are released from…
Protien/Carbohydrates/Alcohol
Protein/ Carbohydrate = 4 kcal
Fat = 9 kcal
Alcohol = 7 kcal
What energy source does muscle switch to after 1-3 days of fasting?
Switches from glucose to FFA.
How long do liver glycogen stores last?
Depleted after 1 day of starvation.
RBC lack mitochondria and therefore cannot use ketones!!!
At which point of fasting does ketones become the main source of energy for the brain?
3 days.
After these are depleted vital protein degradation accelerates leading to organ failure and death.
Ammount of excess stores determines the survival time.
rate limiting step in cholesterol syntehsis?
HMG-CoA reductase converting HMG-CoA to mevalonate.
Statins competitively and reversibly inhibit HMG-CoA!
Hormone sensitive lipase
degradation of the triglycerides stored in adipocytes.
What is the role of LCAT?
Esterfies cholesterol so that it can be carried by VLDL
What apoprotein activates LCAT?
Apo A1
Found in chylomicrons and HDL
Which surface protein is the lipoprotein lipase cofactor?
Apo C
Found in chylomicrons, VLDL and HDL
Which B receptor mediates chylomicron secretion?
Which B receptor mediates LDL reuptake?
B-48 mediates chylomicron secretion and is in chylomicrons!
B-100 Binds the LDL receptor
Found on VDL, IDL, and LDL.
Type I Hyper-chylomicronemia is defined as….
Chylomicrons, TG, and cholesterol increase.
Autosomal recessive
Lipoprotein lipase deficiency causing pancreatitis and hepatosplenomegaly. Will see a creamy layer in blood draws.
Familial hyper cholesterolemia
excessive LDL and cholesterol accumulates in the blood.
autosomal dominant disorder that is absent or defective LDL receptors.
Causes early atherosclerosis (MI before 20)
Hyper trilyceridemia
Excessive VLDL and TG
Autosomal dominant disorder resulting in excessive hepatic VLDL production.
Hypertriglyceridemia >1000 can cause acute pancreatitis.
