what is the first enzyme and step in ethanol metabolism? second step? what is a cofactor in both of these steps? what vitamin does this come from? alcohol dehyrogenase (alcohol to acetaldehyde); acetaldehyde dehydrogenase (acetaldehyde to acetate); NAD+; B3 (niacin)

which is the rate limiting enzyme in ethanol metabolism? where is this enzyme located? where is the other enzyme located? what is the limiting reagent? alcohol dehydrogenase; cytosol; mitochondria; NAD+

what kind of kinetics does alcohol dehydrogenase work under? what are the implications of this? zero order; increased production of NADH no matter the amount of end products produced

what drug blocks alcohol dehydrogenase? what is it used for? fomepizole; antidote for methanol or ethylene glycol poisoning

what drug blocks acetaldehyde dehyrogenase? what are its side effects? disulfiram (antabuse); acetaldehyde accumulate contributing to hangover

what are the three results that come from increased NADH in alcohol metabolism? pyruvate to lactate (results in lactic acidosis and decreased pyruvate for oxaloacetate for gluconeogenesis), increased production of glycerol 3 phosphate from DHAP for TG synthesis; and increased betahydroxybutyrate ketoacid production from increased acetate

what contributes to the acidosis in alcoholism? lactic acidosis and ketoacidosis

what three things contribute to fatty change in the liver in alcoholism? increased G3P for TG synthesis, increased acetyl CoA (Fatty acid synthesis for TG synthesis), and decreased oxidation of FA in the mitochondria due to alcohols toxicity on the mit

what causes hypoglycemia in alcoholism? decreased substrate for gluconeogenesis (pyruvate to lactate and not oxaloacetate); and pyruvate doing only lactic acidosis and not glycolysis

what causes gout in alcoholism? increased acid production competes with uric acid for excretion

what else decreases production of oxaloacetate in alcoholism other than decreased pyruvate? oxaloacetate gets shifted to malate d/t excess NADH

what is hepatocellular steatosis? hepatic fatty change

what liver enzymes are increased in alcoholism? why? AST (mit damage), and GGT (d/t SER hyperplasia d/t induction of p450 generation)

what does alcohol do to the P450 system? induction in chronic alcoholism (increases tolerance); inhibition in acute alcoholism

why is there decreased immunity in kwashiokor and marasmus? no protein!

what explains the fatty change in kwashiokor? abetalipoproteinemia and increased G3P production from all the carbs!

what is the swollen belly from in a child with kwashiokor? ascites from liver damage

how does a kwashiokor patient present? malnutrition, edema (hypoalbuminemia), anemia liver (fatty change), diarrhea d/t no brush border enzymes (no protein!)

what results in marasmus? what kind of muscle wasting? what kind of muscle wasting do you see in kwashiokor? loss of subcutaneous fat, tissue and muscle wasting (somatic muscle); visceral, not somatic

T/F kwashiokor patients are calorie deficient false!

what causes liver damage in kwashiokor? increased TG synthesis from increased Glycerol 3 P and abetalipoproteinemia

what metabolic reactions occur in the cytoplasm? glycolysis, fatty acid synthesis, HMP shunt, protein synthesis (RER), steroid synthesis (SER), glycogenolysis, glycogenesis

which metabolic reactions require both the mit and cytosol? heme synthesis, urea cycle, gluconeogenesis

what is the difference between a kinase and a phophorylase? both add phosphate; phosphorylase uses no ATP and inorganic phosphate

what is the rate determining enzyme in glycolysis? phosphofructokinase 1

what is the rate determining enzyme in gluconeogenesis? fructose 1,6 bisphosphatase

what is the rate determining enzyme in TCA cycle? isocitrate dehydrogenase

what is the rate determining enzyme in glycogen synthesis? glycogen synthase

what is the rate determining enzyme in glycogenolysis? glycogen phosphorylase

what is the rate determining enzyme in HMP shunt? glucose 6 phosphate dehydrogenase

what is the rate determining enzyme in de novo pyrimidine synthesis? carbomyl phosphate synthetase II

what is the rate determining enzyme in de novo purine synthesis? glutamine PRPP amidotransferase

what is the rate determining enzyme in urea cycle? carbomyl phosphate synthetase I

what is the rate determining enzyme in fatty acid synthesis? Acetyl CoA carboxylase

what is the rate determining enzyme in fatty acid oxidation? carnitine acyltransferase I

what is the rate determining enzyme in steroid synthesis? cholesterol synthesis? HMG CoA synthetase; HMG CoA reductase

what is the rate determining enzyme in galactose metabolism? GALT

what is the rate determining enzyme in fructose metabolism? aldolase B

what type of disease is MELAS? what is the clinical presentation? mit encephalopathy, lactic acidosis, stroke like episodes

what type of disease is MERRF? what is the clinical presentation? myoclonus epilepsy

where is there decreased hydrogen concentration in the mit? increased? matrix; intermembrane space

T/F the outer mit membrane is impermeable to ions false! the inner membrane is

which TCA cycle enzyme is found in the inner mit membrane? where are the rest found? succinate hydrogenase; matrix

other than succinate dehydrogenase what other enzymes are found in the inner mit membrane? ATP synthase, ATP-ADP translocase, ETC

what two processes maintain the plasma glucose levels? 1) glycogenolysis (liver only contributes to plasma, muscle keeps it for itself) 2) gluconeogenesis

how many ATP does aerobic metabolism of glucose produce? depending on what? what tissues use which? 32 or 30; malate aspartate shuttle or glycerol 3 phosphate shuttle; heart/liver and muscle

what carries activated Phosphate groups? ATP

what carries electrons (as energy)? NADH, NADPH, FADH2

what carries Acyl (as energy)? coenzyme A and lipoamides

what carries CO2 as energy? biotin

what carries 1 carbon units as energy? tetrahydrofolates

what carries methyl groups as energy? SAM

what carries aldehydes as energry? TPP (thiamine pyrophosphate)

T/F NAD + is used in anabolic processes and NADH is used in catabolic processes False! NAD+ is used in catabolic processes and NADPH is used in anabolic processes

Give examples of the anabolic processes that NADPH participates in. From what process is NADPH produced? steroid, cholesterol FA synthesis; HMP shunt

Other than anabolic processes what else is NADPH used for? respiratory burst, P450, and glutathione reductase

what do hexokinase and glucokinase do? using what? what pathway is this in? phosphorylation of glucose to yield glucose 6 phosphate; ATP; first step of glycolysis

T/F glucokinase is ubiquitous FALSO! hexokinase is; glucokinase only found in liver and beta cells of pancreas

T/F hexokinase has a low affinity and low Vmax FALSO! hexokinase has a HIGH affinity (low Km) and low Vmax

T/F glucokinase has a high affinity and high Vmx falso! glucokinase has a LOW affinity (high Km) and high Vmax

is hexokinase or glucokinase activated by insulin? glucokinase

T/F hexokinase and glucokinase are inhibited by excess glucose 6 phosphate falso! only hexokinase, glucokinase has no feedback imhibition (its a glutton)

T/F glucokinase is a glutton TRUUUEEEEE. fatty mcfatterson

what is the point of having a gluttonous glucokinase in the liver? so that excess glucose can be stored (phosphorylated glucose cant leave) in the liver and saved as a buffer

what is the net production of glycolysis from one glucose? 2 NADH, 2 ATP, 2 pyruvate, 2H+ , 2H20

what is the rate limiting step in glycolysis? what does it do? who activates it? inhibits it? Phosphofructokinase 1; fructose 1 phosphate to fructose 1,6 bisphosphate; enhancers: AMP, fructose 2,6 Bisphosphate; downregulators: citrate, ATP

from what is pyruvate produced in glycolysis? but what enzyme? what enhances that enzyme? downregulates it? phosphoenolpyruvate; pyruvate kinase; fructose 1, 6 BP; ATP, alanine

what ensures that during gluconeogenesis all the ATP wont be used in glycolysis as youre producing it? protein Kinase A inhibits pyruvate kinase also ATP and alanine have negative effects on pyruvate kinase

what control over pyruvate kinase does insulin have? it induces its action!

what converts pyruvate to Acetyl CoA ? what allosterically downregulates this enzyme? Pyruvate dehydrogenase; ATP, NADH, acetyl CoA

by what products are gluconeogenesis and glycolysis linked so that they are not both occurirng at the same time? ATP is an allosteric inhibitor on both phosphofructokinase and pyruvate kinase and pyruvate hydrogenase; and fructose 2,6 BP which is an allosteric enhancer on phosphofructokinase is an allosteric downregulator on fructose 1,6 bisphophatase

what is the first step in glycolysis? phosphorylation of glucose

how does fructose enter glycolysis? galactose? via fructose 1 P by fructokinase in the liver; as glucose 1 by being GALT-ed ;)

T/F galactose is the fastest sugar metabolized. explain. false! fructose because fructokinase in the liver allows it to bypass the rate limiting step in glycolysis (PFK1), and it enters through a different pathway (either through DHAP to glycogenolysis or to glyeraldehyde for glycolysis)

what is fructose 2,6 phosphate? where does it come from? by what enzyme? an allosteric regulator; fructose 1 phosphate; phosphofructokinase 2

what converts fructose 2,6 phosphate back to fructose 2 phosphate? fructose bisphosphatase 2

what two enzymes are the apart of the same complex? what dictates what form they are in? and what dictates that? fructose bisphosphatase 2 and Phosphofructokinase 2; phosphorylation by protein kinase A; inuslin/glucagon ratio

what does fructose 2,6 bisphosphate regulate? positive on phosphofructokinase 1 and negative on fructose 1,6 bisphosphatase

what does fructose 6 phosphate do, depending on what? this depends on if phosphofructokinase 1 is active and this depends on whether or not fructose 2.6 bisphophate is activating it or not- this can only occur if PFK 2 is on and not FBPase 2. then fructose 6 phosphate will participate in glycolysis. Otherwise FBPase2 is on which will result in fructose 6 phosphate going to gluconeogensis because there is no F26BP to activate PFK1

T/F fructose 1,6 bisphophate in involved in allosteric regulation FALSO - fructose 2,6 bisphophate is involved in allosteric regulation

when is there high levels of cAMP? what does this result in? when there is glucagon; protein kinase A activation and thus phosphorylation of the complex resulting in the activation of fructose 2,6 BPase and no PFK2

when are there low levels of cAMP? what does this result in? where there is insulin; low protein kinase A means dePhosphorylation of the complex which results in increased PFK2 which results in more fructose 2,6 bp and thus more PFK1!!

T/F the result of dephosphorylation of PFK2 is activation of PFK1 YES! think it through...

T/F the glycerol phosphate shuttle results more energy than the malate aspartate shuttle. FALSO

other than to glycolysis, where does glucose 6 phosphate get used for? ie what other activated carriers transmit its energy? HMP shunt (to NADPH) and glycogenolysis (as glucose 1 phosphate)

other than glycogenesis and glycolysis, what else is Fructose used for? mannose

what is the pyruvate dehydrogenase complex used for? what is produced in that reaction? conversion of pyruvate to Acetyl CoA; acetyl coA, CO2, and NADH (one of each per pyruvate)

how many enzymes does the pyruvate dehydrogenase complex have? and how many cofactors? where is it located? to what enzyme is it similar to? 3; 5; mit matrix; alpha ketoglutarate dehydrogenase complex

what are the cofactors required for pyruvate dehydrogenase? TPP (from B1- pyrophosphate), FAD (B2), NADH2 (B3), CoA (B5, panothenate), Lipoic Acid

what inhibits pyruvate dehydrogenase? what activates it? NADH, Acetyl CoA, ATP; NAD+, ADP and Ca2+

in the fasting state, what ensures that the pyruvate doesnt get used for TCA cycle? the products of FA oxidation (Acetyl CoA and NADH) phosphorylate pyruvate deyhdrogenase which inactivates it

how are fa oxidation and gluconeogenesis linked, ie what compound makes sure that they occur together and that glycolysis doesnt occur? acetyl coA and NADH inhibit pyruvate dehyrogenase

T/F Ca2+ is an inhibitor on pyruvate deyhdrogenase False- activator! this links glycolysis with muscle contraction

what is the product of alpha ketoglutarate dehdrogenase? succinyl coA

what does arsenic do? how is this important? inhibits lipoic acid; lipoic acid is a cofactor for pyruvate dehydrogenase

what are the symptoms of arsenic poisoning? vomiting, rice water stools, garlic breath

what is the result of pyruvate dehydrogenase deficiency? what causes it? back up of pyruvate and alanine and thus lactic acidosis occurs; can be d/t alcoholism (vit B1 def)

what are two reasons why pyruvate would be pushed to lactate in an alcoholic? increased NADH causes lactate production and pyruvate dehydrogenase def causes increased lactate (d/t thiamine def that often occurs with alcoholics)

what are the findings in pyruvate dehydrogenase def? how do you treat it neurologic defects, myopathy, lactic acidosis; giving ONLY ketogenic nutrient high fat content and aa (lysine and leucine)

which aa are only ketogenic? lysine and leucine

what are the four fates of pyruvate metabolism? pyruvate to alanine (to carry amino groups to liver), pyruvate to OAA for gluconeogenesis (or replenish for TCA cycle), acetyl coA (for TCA cycle transition or FA or chol. synthesis), or the end of anaerobic glycolysis

where is anaerobic glycolysis used often? RBCs, renal medulla, leukocytes, lens, testes, cornea

what is needed for glycolysis to continue? how is this provided in aerobic glycolysis? anaerobic? NAD+; through ETC you produce NAD+; through production of Lactate from pyruvate you create lactate

what is the end of anaerobic glycolysis? pyruvate! (not lactate, that is generate just in order to produce more NAD+)

what does the TCA cycle produce? 3 NADH, 1 FADH2, 2 CO2, 1 GTP = 12 ATP/acetyl CoA

what are the key intermediates in the TCA? Citrate, Isocitrate, alpha ketoglutarate, Succinyl CoA, Succinate, Fumarate, Malate, Oxaloacetate

Where does NADH2 enter ETC? FADH2 Complex I, Complex II (lower energy)

What does the passage of electrons in the ETC result in? formation of a proton gradient that is then used to create ATP through ATP synthase

what are three ways to poison Ox phos? electron transport inhibitors, ATPase inhibitors, Uncoupling agents (increase permeability of the membrane- loss of hydrogen gradient)

What are rotenon, CN, antimycin A, CO? block Electron transport

what does oligomycin do? block ATP synthase resulting in no ATP production and an increased proton gradient

what are uncoupling agents? what is the result? they increase the permeability of the inner mit membrane resulting in a loss of gradient and loss of ATP production BUT electron transport continues! heat is generated instead

T/F O2 consumption stops with uncoupling agents FALSO! because electron transport continues, O2 consumption (last electron acceptor) gets consumed also

list three uncoupling agents 2,4 dinitrophenol, aspirin, and thermogenin (in brown fat)

what are the only substrates for gluconeogenesis? and what products are convertible to it? pyruvate (through OXA); lactate, alanine, malate (and all other TCA intermediates through OXA), glycerol, odd chain fatty acids yield propionyl coA which can be converted to succinyl coA and enter as TCA cycle

T/F acetyl coA is a substrate for gluconeogensis FALSE WE CANT USE even chain fatty acids FOR BLOOD GLUCOSE OR ELSE WE WOULD ALL BE ANOREXIC

what are the four irreversible enzymes of gluconeogenesis and where in the cell are they found? which is deficient in von gierkes disease? pyruvate carboxylase (pyruvate to OXA) (mit), PEP carboxykinase (OXA to PEP) (cyt), Fructose 1,6 bisphophatase (fructose 1,6 bisphosphate to fructose 6 P) (cyt) and glucose 6 phosphatase (in ER); glucose 6 phosphatase

where does gluconeogenesis occur? liver mit and liver cytosol

other than Acetyl coA inhibiting pyruvate dehydrogenase complex, how else is it ensured that gluconeogenesis is occuring during FA oxidation and not glycolysis? Acetyl coA activated pyruvate carboxylase in gluconeogenesis

what is a positive allosteric regulator on pyruvate carboxylase? for what reaction is this? acetyl coA; gluconeogenesis

what two substrates (other than pyruvate) does pyruvate carboxylase require? ATP and biotin

what does PEP carboxykinase require? and for what reaction is this? GTP: gluconeogenesis- OXA to phosphoenolpyruvate

what regulates Fructose 1,6 bisphosphatase? what reaction is it found in? citrate is positive on it, AMP and fructose 2,6 bisphosphate is negative on it; gluconeogenesis

other than in the kidney, where else are gluconeogenesis enzymes found? kidney and intestinal epithelium

why cant muscle participate in gluconeogenesis- what key enzyme does it lack? glucose 6 phosphatase

T/F all products of fats can not enter gluconeogenesis. False! odd chain fatty acids yield one proprionyl coA which can enter the TCA cycle as succinyl coA (and then to OXA)

T/F even chain fatty acids can not produce new glucose since they only yield acetyl coA TRUE

what is one steroid that increases gluconeogenesis? what else does cortisol do that yields hyperglycemia? cortisol; inhibits insulin action

what is the purpose of HMP shunt? to provide NADPH since there is an abundance of glucose 6 phosphate; also yields ribose for nucleotide synthesis and glycolysis intermediates

how many stages are there in HMP shunt? where do they occur? how much energy does HMP shunt use up? 2 oxidative and nonoxidative; cytoplasm (both); none (none produced either- you are simply switching carriers of energy- from glucose 6 phosphate to NADPH)

where does the HMP (pentose phosphate pathway) occur other than in the liver? lactating mammary glands, adrenal cortex (sites of fatty acid or steroid synthesis), RBCS (for glutathione reduction for FR injury)

what enzyme is used in the oxidative phase of HMP shunt? nonoxidative? G6PD dehydrogenase; transketolases

how does lactate contribute to gluconeogenesis? gets converted to pyruvate via the Cori cycle in the liver

name three glucogenic AA and how they enter gluconeogenesis. through what cycle do they enter gluconeogenesis? alanine (through pyruvate), aspartate (through OXA), glutamate (alpha ketoglutarase); TCA

how does glycerol from triacylglycerols in adipose tissue used for gluconeogenesis? gets converted to glycerol 3 P which is then converted to DHAP which then can enter glycolyis

T/F glycogen makes up the back wall of triacylglycerol in fat (TG) false! glycerol; glycogen is what glucose is stored as

What is the first step in the respiratory burst/oxidative burst? in what disease is this deficient? NADPH oxidase; CGD

in what cells does the Respiratory burst occur? where is NADPH located in the cell? what is this reaction important for? Neutrophils and monocytes; membrane bound; immune response by generating Reactive oxygen species

what is this reaction dependent on? oxygen!

what are the first three enzymes in the first three steps in respiratory burst? where do they occur? what do they result in? what does it do? NADPH oxidase, superoxide dismutase, myeloperoxidase; in the phagolysosome; HOCl (bleach); kills!

what are the last three steps of the respiratory burst? why do they need to occur? where do they occur? glutathione peroxidase (catalase) reduces H202 to H20 with glutathione; oxidized glutathione gets reduced by glutathione reductase with NADPH; NAP+ is regenerated to NADPH with Glucose 6 phosphate dehydrogenase; because H2O2 from the resp burts in the phagolysosome- some gets leaked into cell; in the cytosol

how do WBCs of CGD patients do some damage? they use the H2O2 produced by some bacteria to produce bleach with myeloperoxidase which they still have

What kind of bugs are CGD patients screwed with? why do they call it chronic granulamotous disease? catalase positive because they reduce their H2O2 and WBCs cant use that to make bleach; because the way they protect is by building a wall around the organisms with granulomas

what are some catalase positive bugs? s. aureus, Aspergillus

other than the H2O2 produced from the resp burst in infections, what other things does G6PD reproduce NADPH for glutathione reduction for? what cells are particularly vulnerable to these oxidizing agents? sulfonamides, primaquine, dapsone, antiTB drugs, fava beans, LDL; RBCs

what happens in RBCs after their membranes get oxidized? hemolytic anemia due to heinz bodies which are oxidized hemoglobin precipitating within the RBCs

what is the presentation of G6PD deficiency? hemolytic anemia with a blood smear with heinz bodies and bite cells (phagocytic removal of heinz bodies)

what is the most common human enzyme deficiency? why? what is the mode of inheritance of this deficiency? G6PD; provides malarial resistance; X linked recessive

what are the titles of the two types of fructose disorders? which is more serious> essential fructosuria and fructose intolerance; fructose intolerance

T/F fructose disorders are worse than galactose disorders. false

T/F galactose can not get inside cells false; fructose cant get inside cells

what is the metabolism of fructose? fructose gets phosphorylated into fructose 1-P by fructokinase and then fructose 1P gets metabolized into DHAP or glyceraldehyde by aldolase B

what enzyme is deficient in Essential fructosuria? what are the symptoms? fructokinase; benign- fructose in the blood and urine

what enzyme is deficient in Fructose intolerance? what is the result of the enzyme def? what are the symptoms? Aldolase B; Fructose 1 phosphate accumulates which uses up Phosphate and the result is inhibition of gluconeogenesis without phosphate; hypoglycemia, jaundice, cirrhosis, vomitting

how do you treat fructose intolerance? decrease intake of fructose and sucrose (fructose and glucose)

what are the two disorders of galactose metabolism? which is worse? galactokinase deficiency and classic galactosemia; classic galactosemia

what is the metabolism of galactose like? galactose gets converted to galactose 1 Phosphate by galactokinase which then gets turned into glucose 1 phosphate by Galactose 1 Uridyl Transferase (GALT) which also produces UDP Gal which is used for lactose production in the breast; the fate of glucose 1 depends on fasting (glycolysis) or fed state (glycogenesis)

what tissues contain aldose reductase? what does this enzyme do to what? lens and neural tissue; converts galactose to osmotically active galactitol

where does a majority of galactose in our diet come from? lactose (glucose and galactose)

what causes cataracts in a galactose metabolism deficiency? aldose reductase in the lens converts built up galactose to galactitol which is osmotically active

what enzyme is deficient in galactokinase deficiency? what are the symptoms? galactokinase; galactose appears in blood and urine, sometimes infantile cataracts may present as failure to track objects or lack of a social smile

what enzyme is deficient in classic galactosemia? symptoms? treatment? galactose 1 phosphate uridyltransferase (GALT) results in an accumulation of toxic substances; failure to thrive, jaundice, hepatomegaly, infantile cataracts, mental retardation; exclude galactose and lactose from diet

why does galactose def present in newborns> lactose in mothers milk contains galactose

what is another way to trap glucose in cells but not by phosphorylating it? what enzymes are used? by turning it into fructose, but sorbitol first; glucose to sorbitol via aldose reductase and sorbitol to fructose sorbital dehydrogenase

in what tissues can sorbitol accumulate? why? schwann cells, lens, retina, kidneys because they only have aldose reductase and no sorbital dehydrogenase

what is osmotic damage and what molecules cause it? give some examples of osmotic damage- in what disease state do you see these? when water is pulled in; polyols (sugar alcohols); cataracts, retinopathy, peripheral neuropathy all seen in chronic hyperglycemia in diabetes

T/F osmotic damage can not occur in the blood false- high blood levels of fructose, galactose, glucose can result in conversion to osmotically active alcohol forms by aldose reductase!

what is the result of lactase deficiency? in what nationalities is it seen the most? lack of lactase (brush border enzyme) so can not break down lactose (a dissaccharide of galactose and glucose); African Americans and Asians

what are the symptoms involved in lactase deficiency? osmotic diarrhea, bloating, cramps

what is unique about the diarrhea in lactase deficiency? bacteria produce lactate acid and gases from lactose and produce acidic diarrhea and bloating

other than being hereditary, what are two other ways you can have a lack of brush border enzymes? following gastroenteritis and kwashiokor (protein deficiency)

T/F amino acids are found in both L and D forms false- only L form

what are the ketogenic amino acids? leucine and lysine

what are the glucogenic amino acids? met, arg, val, his

what are the glucogenic and ketogenic amino acids? Ile, Phe, Thr, Trp

which amino acids are acidic? are they negatively or positively charged at body pH? asp and glu; negatively

which amino acids are basic? are they negatively or positively charged at body pH? arg, lys, his; positive except His has no charge at body pH

which amino acid is the most basic? arg

which amino acids makes up histones? lys and arg

which amino acids are required during periods of growth? arg and his

what happens in an aminotransferase reaction an aminotransferase enzyme transfers an amino group from an amino acid on to alpha ketoglutarate making it a glutamate (to join the urea cycle or excreted in the kidney) and the amino acid that lost the amino group is then turned into a glycolytic intermediate (pyruvate or oxaloacetate!)

how are nonessential amino acids made? ...

what are the two most common aminotransferase and what amino acids do they turn to what glycolytic intermediates? alanine aminotransferase (ALT) and aspartate aminotransferase (AST); alanine to pyruvate and aspartate to oxaxloacetate

where do aminotransferase reactions occur? and what vitamin cofactor do they require? in hepatocytes; B6

how is excess nitrogen taken care of? excreted from the kidney in the form of urea in hepatocytes

how is urea measured as BUN (blood urea nitrogen)

which are the mitochondrial reactions of the urea cycle? carbomyl phosphate synthetase I turns N acetyl glutamate into carbomyl phosphate and then ornithine transcarbomyalse turns carbomyl phosphate into citrulline (using ornithine)

which is the rate limiting step of the urea cycle? carbomyl phoshpate synthetase I

what two compounds provide the two N's of urea? what else is in urea other than two NH2's? glutamate and aspartate; CO2 provides an ketone

after citrulline is produced and in the cytoplasm what happens next in the urea cycle? citrulline is combined with aspartate to make arginosuccinate which is then split into fumarate (which leaves to enter TCA) and arginine. Arginine is then converted to Ornithine (via arginase) giving off Urea which then goes to the kidney and ornithine reenters the urea cycle (combined with carbomyl phosphate to make citrulline)

what is the most common disorder of the urea cycle? what is the result? what is its mode of inheritance? what is the mode of inheritance of the other urea cycle enzyme def? ornithine transcarbomyalse; orotic aciduria; X linked recessive; autosomal recessive

how is the nitrogen of amino acids transferred to the liver for the urea cycle? explain this process. as alanine; amino acids donate their amino group to alpha ketoglutarate making it glutamate and the aa then becomes an alpha ketoacid (joins TCA cycle); glutamate then converts pyruvate to alanine by donating its amino group to pyruvate (with ALT); alanine then travels through the blood and in the liver gets reconverted back to pyruvate (gluconeogenesis) while giving its amino group to an alpha ketoglutarate which makes glutamate which then joins the urea cycle

what is the primary source of nitrogen in the urea cycle glutamate

T/F all glutamate goes to liver to be turned into urea false; goes to kidney and ammonia is used as a buffer in urine

how can hyperammonia be hereditary? acquired? urea cycle enzyme deficiency (mc: ornithine transcarbamoylase); liver disease- alcoholic cirrhosis and reye's

what does the excess NH4+ in hyperammonia eat up? what is the result? alpha ketoglutarate; no TCA cycle intermediates

what is the treatment of hyperammonia? limit protein in diet; give benzoate or phenylbutyrate which bind amino acids and lead to excretion, lactulose (hydrogen ion binds to ammonia to make excretable ammonium) and neomycin (to kill bacteria that release ammonia from aa)

what are the clinical symptoms of hyperammonemia? tremor (asterixis), slurring of speech, decrease temperature, somnolence, vomitting, cerebral edema, blurring of vision, neural focal deficits

what is the result of arginase deficiency? chorea and spastic paresis

what are the lab findings see in hyperammonemia? increased blood levels of ammonia, decreased BUN

what are the findings in ornthinie transcarbamoylase? orotic acid in blood and urine (from pyrimidine synthesis), decreased BUN, and symptoms of hyperammonemia

what aa does tyrosine come from? phenylaline

from what aa does dopa come from? tyrosine

what converts dopa into melanin? tyrosinase

from what aa does thyroxine come from? tyrosine

from what aa do the catecholamines come from? and what aa does that aa come from? tyrosine; phenylaline

what aa does melanin come from? melatonin? tyrosine; tryptophan

from what aa does niacin come from? with what vitamin cofactor? tryptophan; B6

from what aa do NAD+ and NADP+ come from? tryptophan

from what aa does serotonin come from? what NT is serotonin a precursor for? tryptophan; melatonin

from what aa does histamine come from? with what vitamin cofactors help? histidine; B6

from what aa does porphyrin come from? what is porphyrin the precursor of? glycine; heme

for what three enzymes is arginine a precursor for? Nitric Oxide, creatinine, Urea

what aa (other than glutamate) is a precursor for urea? arginine

what aa is the precursor for NO? arginine

what aa is the precursor for creatinine? arginne

from what aa does glutathione come from? glutamate

from what aa does GABA come from? with what enzyme? and what vit cofactor? what does GABA stand for? glutamate; glutamate decarboxylase; B6; gamma aminobutyrate

what are the three branched aa? isoleucine, valine, leucine

what enzyme is deficient in maple syrup disease? what does it result in? branched chain alpha keto acid dehydrogenase; inability to break down branched chain aa

what aa is the ultimate precursor of catecholamine synthesis? phenylalanine

what enzyme converts phenylalanine to tyrosine? what cofactor is used? phenylalanine hydroxylase; tetrahydrobiopterin factor

what converts tyrosine to DOPA? what cofactor is used? tyrosine hydroxylase; tetrahydrobiopterin factor; NADP+

what is dihydroxyphenylalanine ? DOPA

T/F tyrosinase converts tyrosine to DOPA false; tyrosine hydroxylase

which catecholamine has inhibitory action against acetylcholine? dopamine

what converts dihydrobioterin back to tetrahydrobioterin factor? what energy carrier is used? in what reactions is this cofactor used? dihydropterin reductase; NADP+; phenylalanine to tyrosine and tyrosine to DOP

what converts dopa to dopamine? using what cofactor? dopa decarboxylase; B6

where does catecholamine synthesis take place? neural tissue and adrenal medulla

what converts dopamine to norepinephrine? using what cofactor? dopamine beta hydroxylase; vit C

T/F vit c is needed in catecholamine synthesis true! dopamine to norepinephrine

what negatively regulates dopamine to norepinephrine? carbidopa

what enzyme converts norepinephrine to epinephrine? using what cofactor? phenylethanolamine N-methyl transferase; SAM

what is phenylethanolamine N-methyl transferase located? adrenal medulla

T/F phenylethanolamine N- methyl is only located in the adrenal medulla true (epinephrine only made in the medulla)

what is the degradation product of Norepinephrine? VMA

what is the degradation product of dopamine? HVA

what is the degradation product of epinephrine? metanephrine

what two def. most commonly cause phenylketonuria? phenylalanine hydroxylase or tetrahydrobiopterin factor

what two enzymes are in involved in catecholamine degradation? COMT and MAO

what aa becomes essential with phenylketonuria? tyrosine

what explains the excess phenylketones in the urine in phenylketonuria? phenylalanine build up

give an example of how phenylketonuria is pleiotropic. also have fair skin, blond hair, blue eyes, eczema

what are the findings with phenylketonuria? mental and growth retardation; seizures, fair skin, eczema, musty body odor; neurotoxic ketones and acids stimulate vomitting- can lead to pyloric stenosis

what is the treatment for phenylketonuria? decreased phenylalanine, increase tyrosine

what is Maternal PKU? lack of proper dietary therapy during pregnancy resulting in infant's microcephaly, mental retardation, growth retardation and congenital heart defects

what type of aa is phenylalanine? what implications does this have on the presentation of phenylketonuria? aromatic; musty body odor

what are phenylacetate, phenylactate, and phenylpyruvate? phenylketones that build up in phenylketonuria

what is the mode of inheritance of phenyketonuria? AR

when is phenylketonuria screened? why? 2-3 days after birth because maternal enzyme during fetal like might still be there

what does a deficiency in homogentistic acid oxidase result in? what is this also known as? alkaptonuria; ochronosis

what enzyme is involved in the degradation of tyrosine to fumarate? homogentistic acid oxidase

what builds up in the urine in homogentistic acid oxidase deficiency? what does this result in ? urine turns black on standing

what are the findings in alkaptonuria? why do they occur? dark connective tissue, brown pigmented sclera, debilitating athralgias; homogentistic acid builds up and can be toxic to cartilage

name three causes of albinism. what does albinism increased risk of? tyrosinase deficiency; defective tyrosine transporters; lack of migration of neural crest cells; skin cancer

T/F Albinism is AR false; only the tyrosinase one is- albinism has variable heritability because of locus heterogeneity

T/F Ocular albinism is AR false- X linked recessive

T/F homocysteine gets turned into methionine by homocysteine transferase true

other than being returned to methionine, what else is the fate of homocysteine? through what enzyme? with what cofactor? cystathionine (which then goes to cysteine) via cystathionine reductase; B6

what does SAM turn into after it loses a methyl? how does it get turned back to SAM? homocysteine; homocysteine methyltransferase with B12 and tetrahydrofolate

what three enzyme def. can cause homocysteinura? what is their mode of inheritance? homocysteine methyltransferase, cystathionine reductase, decreased affinity of cystathionine reductase for pyridoxal phosphate; AR

what aa becomes essential with homocystinuria? phenylalaninuria? cysteine; tyrosine

how do you treat homocystinuria due to decreased affinity of cystathionine reductase to B6? by giving high amounts of pyridoxal phosphate in the diet

what are the findings of homocystinuria? increased homocysteine in the urine, mental retardation, osteoporosis, marfanoid habitus, and atherosclerosis

what aa degradation disorder results in atherosclerosis? debiltating arthralgias? osteoporosis? homocystinuria (homocysteine damages endothelial cells); alkaptonuria (tyrosine degradation); homocystinuria

what is the product of odd chain fatty acid synthesis? how does it return to TCA cycle? what cofactor is required? proprionyl coA; through methylmalonyl coA; B12

what is cystinuria due to? hereditary defect of renal tubular amino acid transporter for cysteine , ornithine, lysine and arginine in the PCT of kidnyes

what is the presentation for cystinuria? cystine kidney stones (cystine staghorn calculi)

what is the treatment for cystinuria? acetazolamide to alkalinize the urine

T/F cysteine is a dimer true- of two dimers connected by disulfide bond

what enzyme is necessary for branched aa degradation? what cofactor? what are the branched aa? branche aa alpha ketoacid dehydrogenase; thiamine; Isoleucine, leucine, valine

what builds up in the blood of patients with maple syrup urine disease? urine/poo? what does this cause? alpha ketoacids in the blood; alpha keto acids in the urine/poo smells of maple syrup/burnt sugar

what enzyme is deficient in maple syrup urine disease? branched alpha ketoacid dehydrogenase

what are the findings in maple syrup disease? what should be tried to be given as treatment? CNS defects, mental retardation, death, feeding difficulties, vomiting, hypoglycemia; thiamine

what is hartnup disease? what is the mode of inheritance? defective neutral amino acid transporter on renal and intestinal cells; AR

what aa is most accumulated in hartnup disease? what vitamin becomes deficient? tryptophan; niacin

what is the main clinical presentation of hartnup disease? pellagra

what is the main hormonal regulation of glycogen? glucagon, insulin and epinephrine

T/F the main hormonal regulation of glycogen is glucagon and insulin false- glucagon, insulin and epinephrine

where is glycogen mainly found? liver and skeletal muscle

what is the main use of glycogen? reserve supply of glucose in the fasting state- liver gives to the blood and skeletal muscle uses for itself

T/F increased levels of cAMP results in glycogenolysis true

T/F glucagon works on the liver and muscle to activate glycogenolysis by activating adenylyl cyclase false- just liver

T/F epinephrine works on liver to activate glycogenolysis by activating adenylyl cyclase false- liver and muscle

T/F phosphorylated glycogen phosphorylase is inactive false

what is the first enzyme step in glycogenolysis? what activates it ? inactivates? glycogen phosphorylase; phosphorylation and dephosphorylation

how does glucagon activate glycogenolysis? what regulator does similar? by activating adenylyl cylase which increases cAMP which increases levels of protein kinase A which activates glycogen phosphorylase kinase; epinephrine

how is muscle activity and glycogenolysis coupled in muscle? calcium and calmodulin activate glycogen phosphorylase kinase

T/F inuslin downregulates glycogenolysis by inactivating cAMP false- insulin receptor is not cAMP second receptor but rater tyrosine kinase- which dimerizes and activates a protein phosphatase which de phosphorylates glycogen phosphorylase

how does insulin both deactivate glycogenolysis and activates glycogenesis at same time? by activating protein phosphatase which both dephosphorylates glycogen phosphorylase (deactivating) and dephosphorylates glycogen synthase (activating it )

T/F insulin acts on the liver to deactivate glycogenolysis false- both liver and muscle (unlike glucagon)

T/F glycogen branches have 1,4 bonds and linkages have 1,6 bonds false-opposite

T/F glycogenolysis in skeletal muscle maintains blood sugar false; in hepatocytes

what kind of linkages does glycogen synthase make? branching enzyme? alpha 1,4 linkages; alpha 1,6 linkages

why does branching occur in glycogenesis? branching increases the rate of synthesis and breakdown of glycogen by having more sites to add on to and break off

after glucose 6 P is converted to glucose 1 P , what is the next step in glycogenesis? then what? conversion to UDP glucose via UDP glucose pyrophosphorylase; glycogen synthase (rate limiting step )

what is the main form of glycogenolysis after glycogen phosphorylase? what happens instead in some lysosomes? does this process use glycogen phosphorylase? in what disease is this enzyme deficient? debranching enzyme; alpha 1, 4 glucosidase; no!; Pompes disease

what does glycogen phosphorylase in glycogenolysis create? limit dextrans

what are the glycogen storage disease? what they result in? abnormal glycogen metabolism results in accumulation of glycogen in cells

T/F all the glycogen storage diseases are AR true

what is the fate of glucose from glycogenolysis? glucosekinase to glucose 6 P

how do hepatocytes release glucose 6 P from glycogenolysis into the blood ? in what disease is this enzyme deficient? with glucose 6 phosphatase; Von Gierkes disease

what is the deficient enzyme in Von Gierkes disease? what are the findings? severe fasting hypoglycemia, very high levels glycogen in liver, high blood lactate, hepatomegaly

what is the order of types of glycogen storage disease? Very Poor Carb Metabolism (Von Gierke- Type 1, Pompes- Type II, Cori's- Type III, McArdles disease- Type IV)

What are the findings for Pompe's disease? what is the deficient enzyme? cardiomegaly and systemic findings leading to early death; lysosomal alpha-1,4-glucosidase (acid maltase)

Findings for Cori's disease? deficient enzyme? milder form of type 1 with normal blood lactate levels; debranching enzyme (alpha-1,6 glucosidase)

findings for McArdle's disease? deficient enzyme? high glycogen in muscle, but cannot break it down, leading to painful muscle cramps, myoglobinuria with strenuous exercise, no increase in lactic acid after exercise; skeletal muscle glycogen phophorylase

which glycogen storage disease results in hepatomegaly? von gierkes

which glycogen storage disease causes hypertriglyceridemia? von gierkes

which glycogen storage disease results cardiomegaly? pompes

T/F coris glycogen storage disease has normal lactate levels true

which glycogen storage disease results in no lactic acid after exercise? mcardles disease

what causes the lysosomal storage diseases? deficiencies in one of the many lysosomal enzymes results in accumulation of abnormal metabolic products

which two lysosomal storage disease are XR and not AR? Fabrys Disease and Hunters Syndrome

what is the deficient enzyme in Fabry's disease? accumulated Substrate? alpha galactosidase A; ceramide trihexoside

what is the deficient enzyme in Gauchers disease? accumulated Substrate? Beta glucocerebrosidase; glucocerebroside

what is the deficient enzyme in Niemann Pick disease? accumulated Substrate? Sphingomyelinase; sphingomyelin

what is the deficient enzyme in Tay Sachs disease? accumulated Substrate? Hexosaminidase A; GM2 ganglioside

what is the deficient enzyme in Krabbes disease? accumulated Substrate? Galactocerebrosidase; Galactocerebroside

what is the deficient enzyme in Metachromatic leukodystrophy disease? accumulated Substrate? arylsulfatase A; cerebroside sulfate

what is the findings in Fabrys disease? peripheral neuropathies of hands/feet; angiokeratomas between umbilicus and knees; cardiovascular/renal disease

which is the most common lysosomal storage disease? what are its findings? Gauchers; hepatosplenomegaly, aseptic necrosis of the femur, bone crises, Gauchers cells -crumpled tissue paper looking (fibrillar appearing macrophages in liver, spleen, b.m.)

what are the findings in Niemann Pick disease? progressive neurodegeneration (spasticity d/t UMN disease), hepatosplenomegaly, cherry red spot on macula, foam cells

what are the findings in Tay Sachs disease? progressive neurodegeneration (spasticity d/t UMN disease), NO hepatosplenomegaly, cherry red spot on macula, lysosomes with onion skin, muscle weakness

what are the findings in Krabbes disease? peripheral neuropathy, developmental delay, optic atrophy, globoid cells

what are the findings in Metachromatic leukodystrophy? central and peripheral demyelination with ataxia and dementia

which two lysosomal storage diseases findings are very similar? how do you differentiate them? Niemann pick and Tay Sachs; hepatosplenomegaly or not

what are the mucopolysaccharidoses? which one is XR? AR? what accumulates in them? Hurlers Syndromes;Iduronate sulfatase deficiency; alpha L iduronidase def; heparan sulfate, dermatan sulfate

which Hurlers is milder and presents with no corneal clouding? XR - iduronate sulfatase

what are the findings in AR Hurlers? developmental delay, gargoylism, airway obstruction (d/t short neck), corneal clouding, CAD, hepatosplenomegaly

what lysosomal storage diseases are seen more in Ashkenazi Jew? tay Sachs, Niemann Picks, Gauchers

why is there hepatosplenomegaly in many of the lysosomal storage diseases? because cells of mononuclear phagocytic are esp rich in lysosomes

which lysosomal storage diseases have enzymes that are def in cells that are neuronal mostly? neimann pick and tay sachs

in Fabrys, what accumulates in tissue because fibroblasts express the def enzyme highly? ceramide trihexoside

what is the first step in fatty acid synthesis? where does it occur? where does triacylglycerol synthesis occur? citrate shuttle in the inner mitochondrial membrane transports acetyl coA into the cytoplasm; liver; liver and adipose tissue

what is the rate limiting step in fatty acid synthesis? what four things inhibit this rate limiting step? what stimulates it? acetyl coA carboxylase converting Acetyl coA into malonyl coA; increased AMP, glucagon, epinephrine, palmitate; citrate

where does synthesis of longer chain fatty acids occur? what does it require? SER and mitochondria; NADPH

what is palmitate? saturated or unsaturated? what does that meat? a 16C FA! the product in FA synthesis; saturated; no double bonds

T/F fatty acid synthase requires NADP+ false! NADPH- reductive biosynthesis!

what cofactor does acetyl coA carboxylase require? what does it convert? biotin; rate limiting step in fA synthesis- acetyl coA into malonyl coA

T/F carnitine shuttle is used to transport acetyl coA out of the mitochondria for fatty acid synthesis false! citrate shuttle; carnitine shuttle takes acyl coA into the mit for fatty acid degradation

what does lipolysis generate? and what two regulators activate lipases? triacylglycerols in adipose tissue broken down into glycerol and free fatty acids; growth hormone and epinephrine

what is the fate of the two products of lipolysis? glycerol goes to liver for gluconeogenesis; free fatty acids bind to albumin in blood and travel to cells to be used as for energy

T/F Fatty acid coA synthetase is used in FA synthesis false- FA degradation

what is the first step in FA degradation in the cytosol? FA coA synthetase combines coA with FA to make acyl coA

what is required to get Acyl coA in FA degradation into the mitochondria for beta oxidation to acetyl coA groups? carnitine shuttle

what is carnitine deficiency and what does it result in? inability to transport LCFA into mitochondria results in their build up and causes weakness, hypotonia AND HYPOKETOTIC HYPOGLYCEMIA

what is deficient in someone with hereditary hypoketotic hypoglycemia? carnitine shuttle

why does fa degradation occur in the mitochondria? what does FA degradation produce? what is the fate of this product? because that is where the products will be consumed; acetyl coA; TCA cycle of ketone body production

what is acyl coA dehydrogenase used in? what does a deficiency in this enzyme produce? fatty acid (acyl coA) oxidation to acetyl coA; increase in dicarboxylic acids, and decreased glucose and ketones

walk through the process that adipose tissue makes triacylglycerol. lipoprotein lipases take FA from VLDL and chylomicrons which are then combined with glycerol 3 P (a carb intermediate) to make triacylglycerol

what is the main source of FA? where else can they be released from? synthesis in liver and then hydrolysis of chylomicrons and VLDLs by capillary lipoprotein lipase in peripheral tissue; adipose tissue by lipases

T/F the liver uses ketone bodies for energy false- only muscle and brain have transferase enzyme that converts ketone bodies to acetyl coA

where are ketone bodies made? what is the rate limiting enzyme? what are they made from? mitochondria in liver; HmG CoA synthetase; amino acids and beta oxidation of FA

what does the brain do with ketone bodies? metabolizes them with transferase enzymes to acetyl coA

what are three ketone bodies? which is not detected in urine? which do you see most in alcoholic ketoacidosis? b hydroxybutyrate, acetone, acetoacetate; beta hydroxybutyrate; beta hydroxybutyrate

what is the impetus for ketoacidosis in starvation? alcoholism? oxaloacetate depleted for gluconeogenesis; excess NADH shunts oxaloactetate towards malate

what causes fruity odor in ketoacidosis? acetone

how many calories does one gram of protein generate? carb? fat? 4,4,9

T/F HMG coA reductase is used in KB synthesis false- HMG coA synthase; cholesterol synthesis uses HMG coA reductase

in a 100 meter sprint what is used as energy? in general what is the rule with exercise? what is used in 1000 meter run? Stored ATP, creatine phosphate, anaerobic glycolysis; as distances increase, ATP is obtained from additional resources; above plus ox phos

what is used in a marathon? glycogen and FFA oxidation- glucose conserved for final sprinting!

what are the priorities in fasting and starvation? to supply sufficient glucose to the brain and the RBCs and to preserve protein

what is the source of ATP after a meal? glycolysis and aerobic respiration

what is the source of ATP when you are fasting (in between meals)? hepatic glycogenolysis (mostly), also hepatic gluconeogenesis, adipose release of FFA (minor)

after how long of starvation do glycogen reserves deplete? after this occurs, how are blood glucose levels maintained? 1 day; adipose release of FFA, hepatic gluconeogenesis from peripheral tissue lactate and alanine and from adipose tissue glycerol and propionyl coA

what does adipose tissue contribute for hepatic gluconeogenesis during starvation? muscle? glycerol and propionyl coA; lactate and alanine

after day 3 of starvation, what is the main source of energy? adipose tissue for brain and heart (ketone bodies) and then go to vital protein degradation (organ failure)

what is the rate limiting step in cholesterol synthesis? what does it do? HMG CoA reductase; converts HMG CoA to mevalonate

how much of plasma cholesterol is esterified? and by what? 2/3; LCAT (lecithin cholesterol acyltransferase)

what do statins inhibit? HMG CoA reductase