Biochemistry Metabolism

eesohbel's version from 2015-08-05 21:15

Rate limiting enzymes

gluconeogenesisFructose 1,6 bisphohatase (irreversible)
TCA cycleisocitrate dehydrogenase
glycogenesisglycogen synthase
glycogenolysisglycogen phosphorylase
HMP shuntG6PD
de novo pyrimidine synthesisCPSII
de novo purine synthesisPRPP amidotrasnferase
urea cycleCPSI
fatty acid synthesisacetyl-coA carboxylase
fatty acid oxidationcarnitine acetyltransferase I
ketogenesisHMG CoA synthase
cholesterol synthesisHMG-CoA reductase
Heme synthesisALA synthetase

Regulators of Rate Limiting Enzymes

PFK-1 stimulatedAMP, fructose 2,6 bisphosphate
PFK-1 inhibitedATP, citrate
Frucotse 1, 6 bisphosphatase stimulatedATP, acetyl-CoA
Fructose 1, 6 bisphosphatase inhibitedAMP, fructose 2,6- bisphosphate
isocitrate dehydrogenase stimulatedADP
isocitrate dehydrogenase inhibitedATP, NADH
glycogen synthase stimulatedG6P, insulin, cortisol
glycogen synthase inhibitedepinephrine, glucagon
glycogen phosphorylase stimulatedepinephrine, glucagon, AMP
glycogen phosphorylase inhibitedG6P, insulin, ATP
G6PD stimulatedNADP
G6PD inhibitedNADPH
carbamoyl phosphate synthetase II stimulatedATP
carbamoyl phosphate synthetase II inhibitedUTP
PRPP amidotransferase inhibitedAMP, IMP, GMP
carbamoyl phosphate synthetase I stimulatedn-acetylglutamate
ACC stimulatedinsulin and citrate
ACC inhibited glucagonpalmitoyl-CoA
carnitine actyltransferase I inhibitedmalonyl-CoA
HMG-CoA reductase stimulatedinsulin, thyroxine
HMG-CoA reductase inhibitedglucagon, cholesterol

Gluconeogenesis irreversible enzymes

Question Answer
turns pyruvate into oxaloacetatepyruvate carboxylase
Pyruvate carboxylase allosteric activatoracetyl CoA when is abundant, energy storage time
pyruvate carboxylase/dehydrogenase if brokenhyperalanemia, lactic acidosis and hypoglycemia
turns oxaloacetate in PEPphosphoenolpyruvate carboxykinase
turns fructose 1, 6 bisphosphate into fructose-6-phosphatefructose 1, 6 bisphosphatase
turns glucose-6-phosphate into glucoseglucose-6-phosphatase
requires biotinpyruvate carboxylase
fructose 2, 6 bisphosphate inactivates itfructose 1,6 bisphophatase
where can gluconeogenesis occurliver, kidney, intestinal epithelium
odd chain fatty acids versus even chain fatty acidsodd chain fatty acids can produce new glucose. even chain fatty acids cannot produce new glucose.

Comparison of Well-Fed, Fasting and Starvation

Question Answer
Fed stateincreases insulin decreases CAMP decreases protein kinase A decreases FBPase-2 increases PFK-2, more glycolysis, less gluconeogenesis
Fasting stateincreased glucagon increased CAMP increased protein kinase A increased FBPase-2 decreased PFK-2 less glycolysis more gluconeogenesis
PFK-1 stimulated byFructose 2,6 Bisphosphate and AMP. leads to more glycolysis
When is glycogenesis increasedfed state
When is glycogenolysis increasedfasting state
What happens to glycogenolysis in the starvation statedecreased just enough to supply RBCS
When is beta-oxidation of fatty acids the primary source of fuel for musclesstarvation state
When is ketone body synthesis at its higheststarvation state. Byproduct of acetyl CoA from increased B-oxidation of fatty acids
When does the brain use ketones for fuelstarvation state. Primary fuel
What is the fuel for RBCSalways glucose
When do muscles use ketonefasting state uses some ketones, but more fatty acids
When are fatty acids the primary source of fuel for musclesfasting and starvation state
What is the relationship between hormone sensitive lipase and insulinin the fed state insulin inhibits lipase allowing adipose cells to accumulate triacylglycerol for storage
Epinephrine, growth hormone, and lipaseepinephrine and growth hormone activate lipase during the fasting state to provide energy via fatty acids and glycerol
Adenylate cyclase in glycogen degradationstimulated by glucagon and epinephrine. products inhibited by protein phosphatase A stimulated by insulin
glucagon and epinephrine effects of glycogenincrease glycogenolysis (glucagon goes up in the starving state)
glucocorticoids effect on glycogenincrease glycogen synthesis and accumulation

Pyruvate Dehydrogenase

Question Answer
CofactorsTLC For Nobody (thiamine, lipoic acid, coenzyme A, FAD, NAD)
alpha ketoglutarate dehydrogenase cofactorssame as PD TLC For Nobody (thiamine, lipoic acid, coenzyme A, FAD, NAD)
Pyruvate Dehydrogenase deficiencylactic acidosis pyruvate shunted to lactate to regenerate NAD plus
Presentation of pyruvate dehydrogenase deficiencyneurologic defects
Treatment of pyruvate dehydrogenase deficiencylysine and leucine
arsenic poisoning inhibitspyruvate dehydrogenase
presentation of arsenic poisoninggarlic breath!
If a patient has a high lactate levelthey will have low pyruvate dehydrogenase because they will not be undergoing TCA cycle and have
a high level of lactate dehydrogenase

Biochem UWORLD

Question Answer
in lungs binding oxygen to hemoglobin drives release ofH+ and Co2. haldane effect.
in peripheral tissues high concentrations of C02 and H+ facilitateoxygen unloading from hemoglobin bohr effect

Collagen Synthesis

Question Answer
first step of collagen synthesissignal sequence
scurvy effects what step of collagen synthesishydroxylation of selected proline and lysine reisude
lyslase oxidase coefficientcopper
the only step of collagen synthesis outside of the cellcleavage of procollagen, tropocollagen makes fibrils, lysl oxidase crosslinks the chains together

Electron Transport Chain

Question Answer
uncoupling agentsmake the mitochondria more permeable to H+ goes into matrix and generates heat, ATP synthesis stops, decreases proton gradient, increases O2 consumption, increases permeability of membrane
oligomycininhibits mitochondrial ATP synthase causing an increase in proton gradient. No ATP is produced
rotenone, cyanide, antimycin A, COdirectly inhibit electron transport causing a decrease in proton gradient and block of ATP synthesis


Question Answer
peptide hormones synthesismade in advance stored in secretory vesicles
examples of peptide hormonesinsulin, parathyroid hormone, TSH, FSH, LH
location peptide hormone receptorscell membrane. many are tyrosine kinases aka dimerization internally. insulin tyrosine kinase receptor
prolactin, growth factors and cytokinesutilize tyrosine kinase associated receptors and JAKSTAT pathway


Question Answer
steroid hormone synthesissynthesized on demand from precursors
location of steroid hormone receptorcytoplasm of nucleus
examples of steroid hormonesestrogen, androgens, cortisol
half life of steroid hormoneslong
half life of peptide hormonesshort
catecholaminesmade in advance; stored in secretory vesicles
catecholamines receptorcell membrane
thyroid hormones synthesismade in advance
glucagon binds toGs receptors

Metabolism Sites

Question Answer
FA oxidation (beta-oxidation)mitochondria
Acetyl-CoA productionmitochondria
TCA cycle locationmitochondria
HMP shunt locationcytoplasm
F.A. Synthesiscytoplasm
Protein synthesisRER
Steroid synthesisSER
Location of heme synthesisboth cyto/mito
Location of gluconeogenesiscyto/mito
Location of urea cyclecyto/mito


Question Answer
Carriers of phosphate groupsATP
Electron carriersNADH, FADH2, NADPH
Acyl carrierscoenzyme A, lipoamide
Carriers of biotinCO2
Carriers of 1-carbon unitstetrahydrofolate
Carriers of CH3 groupsSAM
Carriers of aldehydesThiamine Pyrophosphate (TPP)
Use of NAD+ vs NADPHNAD+ used for catabolic processes to carry reducing equivalents away as NADH, NADPH used for anabolic processes like steroid/FA synthesis as supply of reducing equivalent
NADPH is product ofHMP shunt
Uses of NADPHanabolic processes, respiratory burst, p-450, glutathione reductase
Aerobic metabolism ATP yield32 from malate-aspartate shuttle (heart and liver) vs only 30 from glycerol-3P shuttle (muscle)
Shuttle systemsrequired to move NADH across impermeable inner mito membrane, malate-aspartate shuttle is in heart/liver and gives 2.5 ATP/NADH, glycerol-3P shuttle is in muscle and gives 1.5 ATP/NADH


Question Answer
1st step glycolysisconversion of glucose to G6P via hexokinase or glucokinase
Hexokinaseglucose-->G6P, found everywhere, high affinity (low Km), low capacity (low Vmax), un-induced by insulin, feedback inhibition via G6P
Glucokinaseglucose-->G6P, in liver and beta cells of pancreas, low affinity (high Km), high capacity (high Vmax), induced by insulin (GLUcokinase is a GLUtton- has high vmax b/c it can’t be satisfied), NO feedback inhibition (unlike hexokinase), phosphorylates excess glucose (after a meal) to sequester it in liver-->blood glucose buffer
Rate-limiting step of glycolysisPFK-1 converts F6P-->F16BP, inhibited by ATP and citrate, activated by AMP and F2,6BP
Steps of glycolysis requiring ATPhexokinase (glucose-->G6P) and PFK1 (F6P-->F16BP)
PEP-->pyruvatevia pyruvate kinase, produces ATP, inhibited by alanine and ATP, activated by F16BP
Steps of glycolysis producing ATP1,3 BPG-->3-PG via phosphoglycerate kinase, and PEP-->pyruvate via pyruvate kinase
FBPase 2used in fasting state, F2,6BP-->F6P, activated by glucagon-->increased cAMP-->increase PKA-->increase FBPase-2 (decreased PFK2)
PFK2use in fed state, F6P-->F2,6BP (positive feedback to PFK1), insulin-->decreased cAMP-->decreased PKA-->decrease FBPase2 (so increase PFK2)
FBPase2 and PFK2part of same complex but respond in opposite ways to phosphorylation by PKA

Glycolysis (Cont.)

Question Answer
Glycolytic enzyme deficiencyassociated with hemolytic anemia- can’t maintain Na/K ATPase-->RBC swelling/lysis, due to deficiencies in pyruvate kinase usually- RBCs metabolize glucose only anaerobically and depend solely on glycolysis
RBC metabolismmetabolize glucose anaerobically only and depends on glycolysis 100%
Pyruvate dehydrogenase inhibited by?ATP/NADH/acetyl Coa
Pyruvate dehydrogenasepyruvate + CoA + NAD+ --> acetyl CoA + NADH + CO2- requires 5 cofactors of pyrophosphate (B1 thiamine/TPP), FAD (b2 flavin), NAD (B3 niacin), CoA (B5 pantothenate), lipoic acid
Pyruvate dehydrogenase activated by?increased NAD+/NADH ratio, increased AMP, increased Ca
What inhibits lipoic acid?arsenic- will get vomiting, rice water stools, garlic breath
Pyruvate dehydrogenase deficiencycauses backup of substrates (pyruvate and alanine) resulting in lactic acidosis, can be congenital or acquired (alcoholics from b1 def.), will get neurologic defects, tx with intake of ketogenic nutrients only (high fat content or high lysine/leucine) to replace glucose as an E source
Pyruvate dehydrogenase is very similar to what other enzyme complex?alpha-ketoglutarate dehydrog. Complex (converts alpha keto.-->succinyl coA) in krebs
Pyruvate metabolism1. goes to OAA (which replenishes TCA or goes to gluconeo)
2. goes to acetyl CoA for TCA
3. goes to alanine via ALT
4. goes to lactate
Alanine and pyruvate metabolismalanine carries amino groups to the liver from m. (pyruvate --> alanine via ALT)
Cori cycleallows lactate from anaerobic metabolism to go to liver for gluconeogenesis to be glucose source for m./RBCs, shifts metabolic burden to the liver and requires 4 ATP/cycle

TCA Cycle

Question Answer
Pyruvate-->acetyl CoA produces what else1CO2, and 1 NADH, via pyruvate dehydrog.
TCA cycle overall3 NADH (x3ATP) , 1 FADH2 (x 2ATP), 1 GTP, 2 CO2- 12 ATP per acetyl CoA (so 24 for 1 glucose)
TCA cycle occurs where?in mito
Rate limiting step of TCA cycleisocitrate dehydrogenase
Alpha-ketoglutarate dehydrogenaserequires same cofactors as pyruvate dehydrog.- B1, B2, B3, B5, lipoic acid (TPP/flavin/niacin/pantothenate respectively)- converts alpha-keto -->succinyl coA
NADH vs FADH2 in ETCNADh electrons enter mito via malate/aspartate or glycerol 3P shuttles, FADH2 electrons are transferred to complex #2 (at lower E level than NADH), NADH produces 3 ATP, FADH2 produces 2 ATP
step GTP madesuccinyl CoA to succinate
step NADPH madeisocitrate to alpha keto, alpha keto to succinyl CoA, malate to oxaloacetate
why GTP importantGTP used in gluconeo convert oxaloacetate to PEP


Question Answer
Gluconeogenesis enzymesPathway Produces Fresh Glucose- Pyruvate Carboxylase (pyruvate-->OAA)
PEP carboxykinase (OAA-->PEP)
F1,6BPase (F16BP-->F6P)
glucose-6phosphatase (G6P-->glucose)
Def. in gluconeogenic enzymeshypoglycemia
Gluconeogenesis locationoccurs in liver mostly, different enzymes work in either mito or cyto- pyruvate-->OAA (pyruvate carboxylase) is in mito, everything else in cyto
Muscle and gluconeogenesis?muscle can’t participate b/c it doesn’t have glucose 6-phosphatase (G6P-->glucose)
Odd vs even chain FAs for gluconeogenesisodd chain FA yield 1 propionyl CoA during metabolism which can enter TCA (as succinyl coA) and go thru gluconeo to serve as glucose source. even chain FA can’t produce new glucose b/c only yield acetyl CoA equivalents
source of pyruvate from amino acidALT converts alanine to pyruvate. and at same time AKG gets converted to glutamate bc excepts nitrogren from amino acid

HMP Shunt (pentose phosphate pathway)

Question Answer
Pentose pathwayprovides NADPH from abundant glucose-6P, also yields ribose for nucleotide synthesis and glycolytic intermediates
2 phase (ox is irreversible and non-ox is reversible) which both happen in cytoplasm, no ATP used/made
Sites of pentose pathwaylactating mammary glands, RBCs, liver, adrenal cortex
Glucose 6P dehydrogenaseglucose 6P-->NADPH + ribulose 5P + CO2, rate-limiting step in oxidative irreversible part of pentose pathway
Non-oxidative part of pentose pathwayribulose 5P-->ribose 5P + G3P + F6P via transketolases (requires B1)
Enzymes: transketolases, phosphopentose isomerase
Respiratory burstactivation of membrane-bound NADPH-oxidase (neutros and macros), rapid release of reactive oxygen intermediates for immune response
NADPH oxidase deficiencychronic granulomatous disease- these pts use H202 generated by invading organisms and convert it to reactive oxygen species- pts are at risk for infxn by catalase + orgs (S. aureus/aspergillus) b/c they neutralize their own H202 leaving WBCs w/o ROIs for fighting infxn
Glucose 6P dehydrogenase deficiencyXR disorder, more in blacks, increased malarial resistance, no NADPH oxidase to keep glutathione reduced which detoxs free radicals and peroxides, decreased NADPH can cause hemolytic anemia (poor RBC defense)
G6PD deficiency histologybite cells & Heinz bodies
Heinz bodiesoxidized Hb ppt w/in RBC
Bite cellphagocytic removal of Heinz bodies by macros
NADPHused for keeping glutathione reduced which detoxifies free radicals/peroxides and synthesis of cholesterol, decreased NADPH leads to hemolytic anemia (poor RBC defense)

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