METABOLISM SYLLABUS 1: Intro to Metabolism & to Metabolic Regulation by Insulin & Glucagon Flashcards Preview

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Flashcards in METABOLISM SYLLABUS 1: Intro to Metabolism & to Metabolic Regulation by Insulin & Glucagon Deck (50):


sequence of enzyme-catalyzed reactions that brings about the transformation of substrate to product 


major purposes of metabolism?

1) obtain & trap chemical energy from substrates

2) build precursors to macromolecules from substrates 

3) assemble precursors into macromolecules like DNA, glycogen, fat 

4) degrade macromolecules into simpler molecules (like glycogen to glucose)


catabolism vs. anabolism?

catabolism: oxidative breakdown of large macromolecules into smaller, simpler compounds. accompanied by release of free energy, trapping it as ATP - e.g. glucose -> pyruvate


anabolism: enzymatic synthesis of large macromolecules from smaller, simpler precursors. requires energy input - e.g. pyruvate -> glucose


what are amphibolic pathways?

pathways w/ both cataboilc and anabolic components - so can both breakdown and synthesize 

e.g. TCA cycle 


what are the major differences in catabolism and anabolism? why?


2) ENERGETICS: ATP made in catabolism, used in anabolism

3) COFACTORS: NAD+->NADH in catabolism and NADPH -> NADPin anabolism

4) CELLULAR LOCALIZATION: fatty acid oxidation in th emito, fatty acid synthesis in the cyto


identical pathways would prevent regulation, lead to futile cycling and energy waste


what regulates metabolism?

1) availability and concetration of substrates & cofactors 

2) availability and need for energy/ATP 

3) regulatory enzymes 

4) enzyme characteristics 

5) genetic control of amt of enzyme in cell 

6) hormonal regulation 


what is end product feedback inhibition?

principle that anabolic reations are often inhibited by products of that very anabolic reaction 


constituitive vs. adaptive enzymes?

constituitive: enzymes that're always present in constant or near-constant amount; are the more important enzymes 

adaptive: enzymes that can increase or diecrease under certain metabolic conditions, in reaction to a substrate, toxin, or drug which changes their amount in response to a signal



chemical messenger produced in a tissue which will modify a specific metabolic reaction in aonther tissue 

often acts on regulatory enzymes or activates or represses gene expression 


what methods can determine the rate limiting step in a biochemical pathway?

1) assays on relative activites 

2) comparisons of the equilibrium constant to the mass action ratio 


which enzyme in a pathway is the rate limiting enzyme?

enzyme with the lowest relative activity and enzymes with big discrepancy between their Keq and mass action ratio 


what are the rate limiting enzymes of glycolysis?

hexokinase, phosphofructokinase, and pyruvate kinase


what is the effect of an inhibitor on a rate-limiting vs. non-rate-limiting enzyme?

an inhibitor of a rate-limiting enzyme inhibits the overall pathway 

an inhibitor of a non-rate-limiting enzyme inhibits the enzyme but likely not the overall pathway


what enzymes are most likely to be regulated?

relatively low active enzymes and enzymes that fail to maintain equilibrium are likely to be regulated


what is the RBC's only form of energy?

glucose. they do not have mitochondria!


what organi is the major controller of our metabolism?



what processes during glycolysis cause the release of ATP?

susbtrate level phosphorylation or oxidative phosphorylation



what kind of energy does ATP hydrolysis yield?

ATP -> ADP + Phas a deltaG of 7-8 Kcal/mol 

ATP is a high energy compound, and yields a middle-amount of energy compared to other compounds


what happens when ATP is hydrolyzed to ADP? 

what happens when ATP is hydrolyzed to AMP? 

ATP -> ADP + Pdissipates 1 high energy bond 

ATP -> AMP + PiPdissipates 2 high energy bonds 

PiPi, pyrophosphate, is rapidly hydrolyzed to 2 molecules of Pby pyrophosphatase 


what is the structure of NAD+ vs NADH

NAD+ is oxidized, NADH is reduced 



what is the difference between FAD and FADH2?

FAD is oxidized, FADH2 is reduced


what hormones regulate glucose/fatty acid metabolism?

insuiln, glucagon, epinephrine (epi) 

insulin + epi regulate glucose & fatty acid metabolism in mayn tissues 

glucagon acts primarily on the liver & adipose tissue


where is epi produced? when?

in adrenal glands

in response to stress

produced from phenylalanine + tysoine by catacholamine synthesis pathway


where are insulin and glucagon produced? when?

beta (insulin) and alpha (glucagon) cells of the pancrease 

in response to glucose levels: 

INSULIN in response to HIGH glucose (high carb diet) 

GLUCAGON in response to LOW glucose (starvation) 


primary function of insulin?

promote use of glucose 



primary function of glucagon?

promote production of glucose by the liver


what causes type 1 diabetes?

destruction of the B cells of teh pacnreas largely via autoimmune attack on these cells leads to lack of insulin production


what causes type 2 diabetes?

insulin is produced but its effectiveness in enhancing utilization of glucose is decreased, which means increased resistance to actions of insulin 


what do obesity + lack of exercise lead to

type 2 diabetes 


what metabolic problems does diabetes cause

build up of high levels of glucose, esp. in the blood, lead to: 

1) impaired energy production from glucose 

2) fat metabolism's elevated to provide energy, but much fat is oxidized to acidic ketone bodies -> ketosis 

3) high circulating glucose levesl react non-enzymatically w/ prteins/enzymes, glycosylate them, form modified proteins w/ altered funtions 

4) glucose can be reduced by aldose reducatse to sorbitol which increaes osmotic pressure 


what is assay for measuring long-term blood glucose levels?

hemoglobin A1c level - measures that hemoglobin reacts w/ high glucose to form hemoglobin A1c, a glycosylated hemoglobin 

high levels of A1c (> 7 mg%) indicate poor glucose control


what are glucagons functions

1) promotes glucose production in the liver by gluconeogenesis and stimulation of glycogen breakdown

2) increases fatty acid release from triglycerides stored in adipose tissue


glycogen is?

polymer made of many glucose residues 

functions as storage form of glucose


how does glucagon exert its effects?

1) by stimulating the activites of critical enzymes involved in synthesis of glucose & breakdown of glycogen and fat 

2) by transcriptionally activating the genes for these critical enzymes 


what are insulin's main actions?

promotes utilization of glucose by 

1) stimulating glycolysis 

2) stimulating glucose uptake in some tissues like muscle & adipose tissue 

3) stimulating glycogen formation 

4) stimulating fatty acids synthesis from glucose 

5) stimulating protein synthesis 



how does insulin exert its effects?

1) by increasing critical enzyme activities

2) by increasing synthesis of these enzymes 


how do insulin/glucagon work in relation to each other? what pathways does each stimulate/inhibit?

they work in opposite actions - so glucagon does the opposite of everything here


insulin stimulates: glucose-utilizing pathways: glycolysis, glycogen synthesis, fatty acid synthesis 

insulin inhibits: gluconeogenesis, glycogen breakdown, fat breakdown 



how does insulin exert its effects?

via the insulin receptor on the plasma membrane of all tissues 

insulin receptor has 2 alpha + 2 beta subunits. insulin binds alpha subunits, which span membrane, causing tyrosine kinase activity/dimerization of beta subunits, yielding phoshphotyrosine residues 

the phosphotyrosine residues of beta subunit phosphorylate proteins IRS-1 and IRS-2 

phosphorylated IRS-1 and IRS-2 phosphoryate & activate PI# kinase, which activates AKT 

pAKT activates phosphatases, PKC, mTOR, which carry out insulin's actions 

take away: insulin binding stimulates activity of protein phosphatases which carry out downstream actions of insulin


what is the structure of glucagon and epi receptors?

glucagon's are in liver, fat tissues; epi's are widely present 

both are GPCRs with 7 TM spanning loops 

alpha subunit binds GDP in inactive state

activated lgucagon or epi receptor catalyzes exchange of GDP with GTP; follwed by dissociation of beta-gamma subunits to form activate a-GTP G protein 

this activates adenylate cyclase to produce cyclic AMP 

cAMP activates PKA by binding to and dissociating regulatory subunits of PKA 

this frees activte catalytic subunits of PKA 

PKA promotes phoshporylation of many enzymes important in metabolism of glucose and fat - these phoshporylations may activate or inhbit the enzyme or txn factor 


what is the difference in phosphorylation btwn glucagon/epi and insulin?

glucagon and epi: promote phosphrylation of enzymes by activating cAMP-dependent PKA 

insulin: promotes dephosphorylation of enzymes by activating phosphatases eg protein phosphatase 2A 


how is the glucagon/epi signal turned off?

alpha-GTP subunit has a GTPase activity; with time, GTP is hydrolyzed to form alpha-GDP subunit 

this reassociates w/ the Beta-gamma subunits, reestablishes the inactive GDP-alpha-beta-gamma G protein 

eventually, glucagon and epi dissociate from the receptor 

also, cAMP is hydrolyzed by phosphodiesterase to AMP; so cAMP-PKA signal is turned off 



what does insulin do to phoshpodiesterase?

increases phosphodiesterase activity 

phosphodiesterase hydrolyzes cAMP to AMP, turning off the cAMP-PKA signal 

this is a way then that insulin counters the actions of glucagon and epi


what is difference in glucagon/insulin re: 

-where each is made

-what it activates 

-its target 

-when it is released



why do glucose carriers exist?

glucose is highly polar structure - does not get into cells well, considering all of its OH groups 

thus need glucose transporters/carriers to carry glucose from our diet into our cells


how would you prove glucose uptake occurs by a carrier? 

1) kinetics: plot energy vs. velocity curve, see that will eventually saturate the carrier

2) specificity: apply inhibitors and show that carriers are specific re: what they uptake


what are the functions of GLUT1 and GLUT3 carriers?

where do they work? 

when are they saturated?

work in most all tissue - liver, RBC, brain, pancreas, most cells 

do passive carrier-mediate glucose transport

have a low Km/high affinity for glucose (1mM) so catalyze basal glucose uptake 

they thus are almost always saturated at normal glucose levels since normal glucose is 4-8 mM


what is GLUT2 carrier function?

where is it present? 

what is its function?

high kM, low affinity for glucose (15-20 mM kM)

present in liver and pancreas

senses high glucose levels - for pancreas to produce insulin, and liver to utilize high glucose 



does insulin effect rate of glucose uptake by GLUT 1, 2, 3?



where is GLUT4? 


muscle, fat cells 

is the insulin responsive glucose transporter

insulin elevates number of GLUT4 carriers on plasma membrane of muscle and fat cells so glucose uptake is elevated

does this by translocating GLUT4 from Golgi to PM

this is a way to increase glucose uptake in muscle and fat cells

fat converts glucose -> fat, triglycerides 

muscle converts glucose -> glucose, stored as glycogen 



GLUT5 function, location?

GI tract and kidney 

catalyzes active transport of glucoses 

moves molecules against concentration gradient; linked w/ Na+ transport 

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