MCP Flashcards
alpha vs. beta glucose
if the OH is down on Carbon 1, then alpha. if up, then beta
monosaccharide
1 sugar residue
disaccharide
2 sugarrs covalently bound together (lactose, sucrose, etc)
oligosaccharide
2-15 sugars covalently linked
polysaccharide
many sugars covalently bound
glycosidic linkages
named according to the alpha/beta configuration of anomeric carbon and carbon numbers
amylose
linear polymer of glucose
amylopectin
branched polymer of glucose
lactose
disaccharide made of galactose and glucose
sucrose
disaccharide made of glucose and fructose
glycogen
animal way to store glucose. identical structure to amylopectin
cellulose
linear polymer (1,4 beta linked). no enzymes can recognize this linkage so it doesnt get digested
endoglycosidases
cleave internal glycosidic bonds
exoglycosidases
cleave terminal glycosidic bonds
disaccharidases
cleave glycosidic bonds in disaccharides
specificity of glycosidases
based on structure of linkage, sugars in link, and position of linkage in polymer
alpha amylase
hydrolyzes random internal alpha 1,4 bonds in starch
salivary amylase
made by salivary glands in mouth, cleaves starch polymers into smaller polysacc. inactivated by stomach
pancreatic amylase
made in pancreas, secreted into duodenum. produces disaccharides and oligosaccharides
glucoamylase
exoglucosidase. cleaves alpha 1,4 terminal linkages. makes glucose and isomaltose
maltase
cleaves maltose and maltotriose, makes glucose (alpha 1,4)
isomaltase
cleaves isomaltose and alpha dextrins, makes glucose (alpha 1,6)
sucrase
cleaves sucrose, makes glucose and fructose (alpha 1,2)
lactase
cleaves lactose, makes galactose and glucose (beta 1,4)
lactose intolerance
undigested lactose in colon is fermented to make gas and lactic acid, causing diarrhea and stuff
glucose homeostasis: fasting
decreased blood glucose leads to glucagon release into blood. mobilize fuels to increase blood glucose
glucose homeostasis: fed state
increased blood glucose leads to insulin release, promotes fuel storage
glucose –> glucose-6-phosphate
hexokinase. done to keep the glucose in the cell. not done in liver cells, too aggressive
uses ATP
glucose-6-phosphate –> fructose - 6 - phosphate
phosphoglucose isomerase. switches to a 5 member ring, ketose instead of aldose.
Fructose-6-phosphate –> fructose-1,6-bisphosphate
phosphofructokinase (PFK)
transfers a P from ATP
fructose-1,6-bisphosphate –> glyceraldehyde-3-phosphate and dihydroxyacetone phosphate (GAP and DHAP)
aldolase.
cleves into two trioses. easy to interconvert between GAP and DHAP (triose-P isomerase)
GAP –> 1,3-bisphosphoglycerate
GAP dehydrogenase
oxidizes GAP and makes NADH
1,3-BPG –> 3-phosphoglycerate
phosphoglycerate kinase
makes an ATP. since there were two GAPs, we get 2 ATP to make up for the beginning. phosphoglycerate mutase moves the phosphate to the 2 carbon
2-phosphoglycerate –> phosphoenolpyruvate
enolase. remove a water molecule
phosphoenolpyruvate –> pyruvate
pyruvate kinase.
makes ATP, last step in glycolytic pathway. substrate level phosphorylation
how to regenerate NAD+?
NADH goes to mitochondrion so it can be used in the electron transport chain and give back NAD+
glycogen branching enzyme
needs a chain of at least 11 residues, counts off 6 residues, clips it, and attaches that 7 chain to another chain
von gierke disease
defective glucose-6-phosphatase enzyme. affects liver and kidney. raises amount of glycogen causing massive enlargement of liver
anderson disease
defective branching enzyme. affects liver and spleen, makes very long polymers of glycogen. causes cirrhosis of the liver and death before age of 2
mcardle disease
issue with phosphorylase enzyme. affects muscle, ups the amount of glycogen. inability to perform strenuous exercise
where does citric acid cycle occur
matrix of mitochon
functions of citric acid cycle
converts a number of fuels to a common mobile fuel (NADH)
serves as final meeting place of nearly all oxidizable substrates
provides intermediates for biosynthesis
pyruvate –> acetyl-CoA
pyruvate dehydrogenase complex. E1 does condensation/decarbox (TPP). E2 does oxidative transfer and transacetylation (Lipoamide). E3 does dehydrogenation (FAD)
citrate synthetase
condensation and hydrolysis of thioester (acetyl CoA + oxaloacetate –> citrate + CoA
aconitase
dehhydration and hydration. Citrate –> isocitrate
isocitrate dehydrogenase
oxidative decarboxylation. isocitrate –> alpha ketoglutarate
alpha ketoglutarate dehydrogenaase complex
oxidative decarbox and formation of thioester. Alpha ketoglut –> succinyl CoA
succinyl CoA synthetase
thioester cleavage coupled to GTP synth. Succinyl CoA –> Succinate
succinate dehydrogenase, fumarase, malate dehydrogenase
oxidation, hydration, oxidation
succinate –> fumarate –> Malate –> oxaloacetate
pyruvate carboxylase
starts the gluconeogenesis pathway, only found in mitochondria (pyruvate –> oxaloacetate) uses ATP
oxaloacetate –> phosphoenolpyruvate (PEP)
PEPCK is the enzyme. releases CO2, uses GTP
mal/asp shuttle
transports OAA (oxaloacetate) by first reducing to malate so it can cross membrane
cori cycle
lactate converting to glucose to go back into the blood stream
respiratory chain
embedded in inner mitochon membrane. not limited by rate of diffusion, and the intermediates are stable.
flavins
redox center. 2 electron donor/acceptor. (FMN/FMNH2)
iron-sulfur centers
accept e- from flavins and Q. 1 electron donor/acceptor.
ubiquinone
2 electron donor/acceptor. 1,6-addition. hydrophobic. functions as electron buffer
hemes
1 electron donor/acceptor.
copper centers
1 electron donor/acceptor in cytochrome oxidase. only redox centers in the chain that have open coordination sites that will allow O2 to bind. this prevents short circuiting the transport pathway which would decrease efficiency of the energy coupling`
ATP synthase
F0 and F1. F1 contains 3 catalytic sites for ATP synthesis. Connected to F0 by a central stalk and an external stalk. F0 is hydrophobic and carries protons from one site to the other.
respiratory control
an electrochem gradient functions as a common intermediate linking oxidation to phosphorylation. Oxygen consumption is coupled to ATP synthesis. rate of respiration is controlled by availability of ADP.
mitchell’s chemiosmotic theory
delocalized electrochem gradient is a required intermediate in coupling exergonic redox to endergonic synth of ATP.
Q cycle
- iron sulfur center of dehydrogenase and Cyt bH donate 1 e- each to Q. Q also picks up 2 protons from outside.
- QH2 travels to outside surface to be oxidized.
- 1 e- is transferred to the iron sulfur center of the b/c1 complex and another to Cyt bL. due to this removal of 2 e-, the 2 H+ are released to the outside to give oxidized Q.
- Q then travels back to the inside surface to begin the next cycle, and the e- is passed from bL to bH.
proton pumps
the loop cant work in cytochrome oxidase due to no H+ donor/acceptor. here an indirect coupling mech is used. proton pumps couple proton transport indirectly to exergonic redox rxns through protein conformational changes
binding change mechanism
energization needed to promote release of ATP from binding site. tight binding of substrate and product release occur simultaneously on separate but interacting sites. coupling of H_ transport to binding changes requires rotation of subunits
role of the transmembrane gradient
ATP synth, transport of ADP and ATP, Heat, rotation of bacterial flagella, antiports/symports cations/sugars/AAs, transports phosphate, acidification of endomembrane compartments
rate limiting enzymes
enzymes that operate far from equilibrium. modulation of these enzyme’s activity will have a significant effect on flux through a pathway
rate limiting glycolytic steps
hexokinase, phosphofructokinase, and pyruvate kinase (1, 3, 10)
optimal point to regulate in glycolysis/gluconeogenesis pathway
PFK (phosphofructokinase). pyruvate kinase is also ok
inhibitor of PFK
ATP (allosteric inhibitor, feedback inhibitor) places a negative charge (destabilizing) near the negatively charged substrate
activator of PFK
AMP. places a stabilizing positive charge near the negatively charged substrate. F2,6BP is also an activator as it competes with ATP
inhibitors of FBPase
AMP and F2,6BP. slowing gluconeogenesis when glycolysis is active.
F2,6P
made when enzyme is dephosphorylated, broken down when enzyme is phosphorylated. regulated by hormones.
inhibitors of pyruvate kinase
acetyl coA, ATP, cAMP-dependent phosphorylation. inhibited by feedback inhibitors
activators of pyruvate kinase
FBP (earlier substrate in the pathway)
activator of pyruvate carboxylase
Acetyl CoA
phosphorylase
when Glu is low, phosphorylase is in phosph form, and is in active form. when Glu is high, ATP and G6P is high and dephosph phosphorylase is in inactive form.
pyruvate dehydrogenase complex regulation
kinase activated by NADH and acetyl CoA, inactivating E1 by phosphorylating it. Pyruvate and ADP inhibit the kinase. Phosphatase is activated by Ca ions to make E1 active.
standard state (chemist’s)
all substrates and products are at 1M concentration and the temp is specified
delta G = delta G (biochem)
when substrate and product = 1M and H20 = 55.5M and H+ = 10^-7M
limitations for delta G calcs
deviations from standard state for H20 and H+, special environments at catalytic sites, concentrations of substrate and product not able to be measured
why store metabolic energy as fat?
lower oxidation state, fat is stored in an anhydrous state (light weight), fats dont participate in the cells osmotic balance so they can be stored to a large fraction of the cell volume
two sources of non-esterified fatty acids
dietary fat via exogenous pathway, and FA synthesized de novo made via endogenous pathway
fat as fuel
free fatty acids are released from Triglycerides. they are broken down to acetyl-CoA and enter the TCA cycle, giving ATP
digestion of triglycerides
bile is a detergent. needed for lipid dispersion. bile contains bile acids, phosphatidyl choline, and cholesterol.
pancreatic lipase
digests triglycerides in lipid droplets. requires formation of a complex with colipase and a droplet of lipid, stabilizing the open conformation and allowing access to substrate while shielding against bile salts that inactivate the enzyme
absorption of lipid digestion products
bile acids form mixed micelles with the digestion products (2-MAG and NEFA) which allows them to translocate across the stationary aqueous boundary layer at the intestinal wall. use fatty acid transport protein family (FATP5) to get in cell. AQP3, an aquaporin, mediates glycerol transport.
steatorrhea
excessively fatty stools. caused by failure of bile production, blockage of bile flow, exocrine pancreas dysfunction or obstruction of pancreatic dut, failure of uptake into intestinal mucosal cells (enterocytes)
acyl-CoA synthetase
catalyzes formation of acyl-coA derivatives of long chain fatty acids
acyltransferases
catalyze the transfer of 2 LCFA moieties to 2-MAG
chylomicrons
lipoproteins used to transport TG through lymph and blood
Apo-B48
principal protein component of chlyomicrons as they are produced in the intestinal mucosa
lipoprotein lipase
clears FAs from lipoproteins. located in the capillary endothelial walls of various tissues
essential amino acids
histidine, isoleucine, eucine, lysine, methionine, phenylalanine, threonine, tryptophan, valine, arginine
most abundant AAs in serum
glutamine and alanine
hartnup’s disease
defect in transport system for neutral and aromatic amino acids, including tryptophan from the gut and renal tubules. Diarrhea, dematitis, dementia, death. treat with niacin
cystinuria
defect in the transport system for basic amino acids and cystine from gut and renal tubules. symptoms include crustals leading to UTIs and kidney stones. treat with fluid and penicillamine
cystic fibrosis problems with amino acid transportation
defect in chloride channels in pancreatic secretory ducts, they harden and block leading to a lack of pancreatic enzymes
how to get rid of ammonia ions
3 ways to remove ammonia ions
glutamate dehydrogenase (turns alpha ketoglutarate into glutamate), glutamine synthase (reversible by glutaminase, turns glutamate into glutamine) and carbamoyl phosphate synthase 1 and 2.
done in order to remove free amonia ions.
transamination
transfer of an amino group from an AA to an alpha keto acid to form a new AA and a new keto acid
pridoxal phosphate (vitamin b6)
essential cofactor for all transamination
oxidative deamination by glutamate dehydrogenase
located in mitochondria. Uses either NAD or NADP as cofactor. activated by ADP and GDP and inhibited by GTP/ATP
amino acid oxidases
L and D amino acid oxidases occur in kidneys and liver. use flavins as cofactors, and turn an AA and water into corresponding keto acid and ammonia
direct deamination by dehydratases
hydroxyl side chain of threonine and serine allow them to be directly deaminated. pyridoxal phosphate is cofactor
desulfhydrases
removes ammonia and sulfur from homocysteine (pyridoxal phosphate cofactor)
urea cycle
conversion of free ammonia to urea
carbamoylphosphate
formed from ammonia and CO2 through carbamoylphosphate synthetase. uses 2 ATP
citrulline
formed from carbamoylphosphate and ornithine. catalyzed by OTC (X linked gene)
argininosuccinate
formed from citrulline and aspartate. argininosuccinate synthetase. 1 ATP needed
arginine and fumarate
formed from cleavage of argininosuccinate, done by argininosuccinate lysase
urea and ornithine
formed from cleavage of arginine. arginase enzyme.
regulation of urea cycle
protein free diet-levels of urea cycle enzymes decline. high protein diet- or starvation, urea cycle enzymes go way up
ammonia toxicity
seen in liver failure, inborn errors of metabolism. occurs through reduced flux of TCA cycle due to brain making glutamate. glutamate turns to glutamine from excess NH3, and leaves brain in exchange for tryptophan. trp goes to serotonin, and you get sleepy
glucagenic
can be converted to glyolytic intermediates
ketogenic
end up in acyl coA or acetyl CoA. once you get to acetyl CoA, you cant go back to glucose
alanine transaminase (ALT)
alanine is a glucogenic AA. common AA in the blood. gets converted to glutamate by ALT. efficient way to send carbon and ammonia from tissue
serine dehydratase
removes a water from serine, then adds it back and removes NH3 to get pyruvate. glucogenic
desulfhydrase
cysteine –> pyruvate. glucagenic
serine hydroxymethyl transferase
serine to glycine with THF as a cofactor. THF is an important carbon carrier. chemo can block this folate synthesis. this is a reversible reaction
threonine degradation
glucogenic (goes to glycine). makes acetyl CoA, so it is ketogenic too! not reversible. uses NAD->NADH
asparaginase
asparagine –> aspartate. removes an NH4, adds a water
histidine degradation
glucogenic. goes to glutamate, using THF as cofactor again. another source of charged folate
arginine and proline degradation
both go to glutamic acid and go through a common intermediate, glutamic acid semialdehyde. proline is reversible, but to remake arginine you need to go through urea cycle again
branch chain amino acid degradation
valine, isoleucine, leucine. uses branch chain transaminase. if you inhibit these enzymes, you can build up leucine which promotes insulin insensitivity and weight loss. valine is glucogenic, isoleucine is both, and leucine is ketogenic
alpha keto acid dehydrogenase
second enzyme in branch chain AA degradation. if defectve, can lead to a build up of alpha keto acid, leading to maple syrup urine. giving one of the branch chain AAs will cure this
phenylalanine and tyrosine degradation
ketogenic. if you have a deficiency of phenylalanine hydroxylase, this leads to PKU and inhibits brain development
regeneration of BH4
uses dihydrobiopterin reductase to go from BH2 to BH4. some people can have a deficiency in this enzyme, and BH4 is needed in other reactions in the body
homogentisic acid 1,2-dioxygenase defect
alkaptonuria. usually converts homogentisic acid to acetoacetic acid. the acid deposits in the cartilege and leads to arthritis
serine synthesis
made out of glycolysis and glycolytic intermediates. main source of 1 carbon groups.
cysteine synthesis
made from methionine
homocystinuria
high levels of homocysteine. increased risk of atherosclerosis. leads to oxidized LDL. severe heart disease in young age (teens, early 20s)
cystathionuria
high levels of cystathionine and homocysteine. same symptoms as homocystinuria, but later deaths
what promotes fat storage
insulin
perilipins
proteins that coat the surface of peripheral lipid droplets. targets for cAMP-dependent protein kinase. they get phosphorylated by protein kinase A which allows access to the droplet due to a conformation change
step 1 of beta oxidation: activation of fatty acid
fatty acid –> acyl CoA + AMP. Acyl-CoA synthetase. gets energy by splitting a pyrophosphate into 2 phosphate groups
step 2 of beta oxidation: transfer of LCFA moiety from CoA
transfers LCFA to carnitine. uses Acyl-CoA-carnitine transacylaase (CPT I). gives you a fatty acyl carnitine. happens in mitochondial inter membrane space, the acyl carnitine can transfer across the inner mitochon membrane. here, carnitine palmitoyl transferase 2 makes acyl CoA again.
malonyl-CoA
inhibits CPT I. malonyl CoA is the product of the first committed step in FA biosynthesis.
step 3 of beta oxidation: oxidize bond to a double bond
acyl-CoA dehydrogenase does this. different isoenzymes for different length fatty acids. produces an FADH which will eventually make ATP
step 4 of beta oxidation: adding a water across the double bond yielding beta hydroxy acyl CoA
enoyl-CoA hydratase. adds a hydroxyl group to the beta carbon
step 5 of beta oxidation: oxidize the beta hydroxyl to a beta ketoacyl-CoA
done using hydroxyacyl CoA dehydrogenase. makes a beta ketone
step 6 of beta oxidation: thiolysis reaction
splits off acetyl CoA and leaving acyl CoA shorter by 2 carbons. done using thiolase enzyme. each round makes another acetyl coA
comparison with glycolysis
glycolysis is 6 ATP per carbon, beta oxidation is 8 ATP per carbon
ketogenesis
only happens in the liver. produced from acetyl-CoA. KB not used as fuel by liver, exported by liver as water-soluble equivalents of FA.
regulation of ketone body metabolism
in fasting, low concentrations of TCA cycle intermediates. Acetyl-CoA diverted to KB. Ketosis (state of making KB) begins after overnight fast.
too little glucose = ketogenesis. too little oxaloacetate = ketogenesis
ketone overproduction
problem in type 1 diabetes. zero insulin, so there is no break on lipolysis. no insulin to counter regulate. max production of NEFAs. liver cant handle it, so excess FA make ketone bodies. other tissues havent upregualted the enzymes they need to break down KB, so they end up going to kidney, who cant filter them all, so they go to blood
formation of dopa
tyrosine –> dopa
uses tyrosine hydroxylase
needs tetrahydrobiopterin. this is the rate limiting step.
formation of dopamine
AA decarboxylase forms dopamine from dopa
formation of norepinephrine
mixed function oxidase hydroxylates dopamine on the side chain to yield norepinephrine
formation of epinephrine
methylated by methyltransferase to form epinephrine. SAM used as methyl donor
biosynthesis of melanins
made in melanocytes (pigment producing cells). made from tyrosine. defect = albinism
what AA is the precursor of serotonin, melatonin, and NAD+?
tryptophan
pellagra
deficiency of tryptophan leading to a deficiency of niacin. symptoms are dermatitis, dementia, diarrhea, and death
GABA production
made from glutamate by glutamate decarboxylase
Histamine production
made from histidine. histidine decarboxylase catalyzes the formation of histamine
what does the body need single carbon fragments for?
formation of methionine from homocysteine, biosynth of purines and pyrimidines, and biosynth of glycine from CO2 and NH4 by glycine synthase
biotin
carrier of CO2, the most oxidized one carbon group
THF (tetrahydrofolate)
carries one carbon groups of all oxidation states except CO2. can serve as an acceptor of one carbon fragments in degradative reactions and as a donor of one carbon fragments in biosynth reactions
synthesis of THF
get folate from the diet. usually ingested as polyglutamines, which get cleaved by conjugase leaving folic acid. intestinal mucosal cells reduce folic acid to THF using dihydrofolic acid reductase. this carbon is then bound to either N5, N10, or both in 3 diff oxidation states
problem with N5-methyl form of THF
N5 methyl form is used in a rxn to make methioninesome people have a deficiency in the enzyme that makes this. they have hgiher risk of heart disease and a lower risk of colon cancer
interconversion of serine and glycine
uses N5,N10 methylene THF.
drugs that inhibit dihydrofolate reductase
aminopterin and methotrexate. leads to low levels of THF in tumors which is needed for DNA replication. other things that have low levels of THF are also impacted, like bone marrow, hair follicles, and GI mucosa
S-adenosylmethionine
major carrier of methyl groups. involved in the following reactions
- norepi to epi
- guanidinoacetate to creatine
- acetylserotonin to melatonin
- phosphatidylethanolamine to phosphatidylcholine
- methylation of DNA
homocysteine production
methionine –> S-adenosylmethionine.
methyl transfer from S-adenosylmethionine to acceptor molecule.
S-adenosylhomocysteine is hydrolyzed to adenosine and homocysteine.
Methionine can be regenerated from homocystein using homocysteine methyl transferase
elevated levels of homocysteine
strongly correlated with high risk of atherosclerosis. vitamin B12 can help with this
production of cysteine from homocysteine
homocysteine and serine condense to make cystathionine using cystathionine synthase. cystathionine is hydrolyzed to form cysteine and homoserine which goes to alpha ketobutyrate using cystathionase
homocystinuria
caused by inability to convert homocysteine to methionine due to defect in methyltransferase or deficiency of THF or methylcobalamin
vitamin b12 (cobalamin)
coenzyme. central core of cobalt. several forms, vary by the group attached to the fifth bond above the plain of the ring.
reactions involving cobalamin
conversion of L-methylmalonyl CoA to succinyl CoA
action of homocysteine methyltransferase
megablastic anemia
deficiency of B12 and THF. immature redblood cells are released into bloodstream
demyelination and degradation of spinal cord
caused by b12 deficiency
folate trap
occurs when b12 is deficient. causes a folate deficiency by trapping folate in the N5 methyl form. this is then manifested as anemia. if folate is supplemented, b12 is still deficient and you get brain problems without anemia
source of NADPH for FA synth
pentose phosphate pathway. also malic enzyme
2 enzymes needed for FA synth
acetyl CoA carboxylase and Fatty Acid synthase
rate controlling step in FA synth?
Acetyl CoA carboxylase
acetyl CoA carboxylase (ACC)
converts acetyl CoA to malonyl CoA. Uses ATP, and biotin as a cofactor.
regulation of acetyl CoA carboxylase
regulated by citrate which causes it to polymerize, activating it. insulin activates, along with caloric intake.
glucagon/epi levels inactivate it. palmitoyl CoA inactivates it. AMP inactivates
Fatty acid synthase (FAS)
homodimer. each subunit has 3 catalytic domains in the N portion, and a C portion with 4 domains.
phosphopantethenyl residue of FAS
derived from pantothenic acid. linked to a serine in the acyl carrier protein portion of FAS, and the SH group reacts with a malonyl CoA to form a thioester bond
steps in FA synth
- activation 2. condensation (ketone C=O) 3. reduction (C-OH) 4. dehydration (C=C) 5. reduction (C-C)
each cycle adds carbons until it gets to 16 carbons (palmitate)
elongation of fatty acids
palmitate gets activated to palmitoyl-CoA. elongated 2 carbons at a time in the ER by enzymes called elongases.
desaturation of fatty acids.
oxidation of fatty acids resulting in cis double bonds. creates lipids of increasing structural and functional complexity with distinct biological roles. uses desaturases. regulated in response to diet. decrease during starvation, increase with feeding.
monounsaturdated fatty acids (MUFAs)
3 distinct desaturases. delta 9, 6, and 5 desaturase. most common desaturation reactions involve an oxidation leading to a double bond between C9 and C10.
polyunsaturated fatty acids (PUFAs)
PUFAs with double bonds 3 or 6 carbons from methyl end are needed for eicosinoid synth. must come from diet.
lineoleic acid to arachidonic acid
elongation and desaturation.
eicosanoids
prostaglandins, thromboxanes, and leukotrienes. derived from arachidonic acid. hormone like effects on cells.
cyclic pathway for eicosanoid synth
forms prostaglandins, thromboxanes, and prostacyclins
linear pathway for eico synth
forms leukotriens, HETEs, and lipoxins from HPETE
cytochrome p450 pathway of eico synth
makes epoxides
COX-1 and 2
COX1 is in all tissues. COX 2 is regulated by cytokins and growth factors, and responds to inflammation
prostaglandin and thromboxanes
reciprocal regulation
agents that promote catabolism inhibit anabolism
catabolic enzymes
active when phosphorylated.
glycogen phosphorylase, phosphorylase kinase, hormone-sensitive lipase
anabolic enzymes
inactive when phosphorylated
acetyl-CoA carboxylase, glycogen synthase, HMG-CoA reductase
futile cycle in adipocytes during fasting conditions
cAMP turns on lipolysis, but also turns on CREB, which causes fats to be stored. futile cycle, meaning fat is made and broken down in equal parts using ATP. thought to act as a brake on lipolysis so NEFAs aren’t released too quickly
starved state
more KB production, less urea formation, less protein breakdown, less glucose formation. brain can utilize KB now for fuel. glycerol, AA, and lactate are now converted to glucose
epinephrine
stimulates glycogen breakdown in muscle and liver, gluconeogenesis in liver, and lipolysis in adipose tissue
glucocorticoids
stim lipolysis in adipose tissue and the release of AA from muscle protein. in liver, they stim gluconeogenesis and stim synthesis of glycogen
PRPP
an intermediate of major significance in nucleotide metabolism
required in de novo synth of pyrimidine and purine nucleotides. salvage pathways of purine nucleotides. biosynth of nucleotide coenzymes NAD and FAD
5’-phosphoribosyl-1-pyrophosphate
PRPP formation
formed from ribose-5-phosphate and ATP. catalyzed by PRPP synthetase
synth of purines
built on a molecule of PRPP. precursors of the ring are glutamine, glycine, CO2, aspartate, and 2 one carbon fragments.
IMP formation
10 step process using 6 phosphate bonds for energy. first step is rate limiting and regulated stp. 2 steps need folate and are blocked by drugs that block folate synth. nucleotide ring is made from glutamine, glycine, CO2, aspartate, and 2 1 carbon fragments. 2 steps require glutamine amino transfer reactions, inhibited by azaserine. expensive process, would rather salvage.
synth of AMP from IMP
adenylosuccinate formed by adding aspartate to IMP. fumarate is cleaved to give AMP. GTP is cleaved to make this.
synth of GMP from IMP
xanthylate or XMP is formed by oxidation of IMP. an amino group from glutamine is then added to give GMP. ATP is cleaved to make this
what regulates synth of purine nucleotides?
feedback inhibition. PRPP synthetase and PRPP amidotransferase (2 enzymes that make IMP) are regulated by IMP, GMP, and AMP.
HGPRT
catalyzes formation of nucleotides from either hypoxanthine or guanine. inhibited by IMP and GMP..
defects in HGPRT can lead to gout
APRT
catalyzes formation of AMP from adenine. inhibited by AMP
Nucleoside kinase
makes AMP + ADP from adenosine + ATP
purinosome
localization of purine biosynthetic machinery. presence of this organelle is regulated by purine abundance
synth of pyrimidine nucleotides
ring is formed first, then it reacts with PRPP. precursors of the ring are carbamoylphosphate and aspartate. makes UMP
carbamoylphosphate
made in cytosol from glutamine and CO2. also made in liver as in intermediate in urea synth
orotic aciduria
genetic disorder of pyrimidine biosynth. orotic acid accumulates in blood and is excreted in urine. give uridine or cytidine to fix.
synth of UTP from UMP
First step done by UMP kinase, second done by nucleoside diphosphate kinase. addition of 2 ATPs
regulation of pyrimidine synth
a single protein does the first 3 steps, the last 2 steps done by another protein. pryimidines decrease enzyme activity, but molecular basis is unknown
uracil to UMP
2 sequential reactions. 1st is a reverse of a reaction that occurs in the degradation of nucleotides. Uracil -> uridine. Then an ATP is added by uridine kinase to give UMP. uridine kinase can also phosphorylate cytidine.
formation of deoxyribonucleotides
formed by reduction of ribonucleoside diphosphates. done by ribonucleotide reductase. products are dADP, dCDP, dGDP, dUDP. inhibited by hodryoxyurea
dTMP formation
formed from dUMP, catayzed by thymidylate synthase. only made by cells in S phase
5-fluorouracil
anticancer agent. converts to F-UMP in cells. can be turned to F-dUMP. prevents synthesis of dTMP
methotrexate
analog of folic acid that inhibits dihydrofolate reductase. cant make THF, so dTMP synth is inhibited
salvage of thymine deoxyribonucleotides
thymine phosphorylase and thymadine kinase give dTMP
nucleotidases
remove 5’-phosphates from purine and pyrimidine ribo and deoxyribonucleotides, converting them to ribo and deoxyribonucleosides
nucleoside phosphorylases
catalyze the phosphorolysis of nucleosides to free bases and ribose or deoxyribose 1-phosphate
purine degradation
gives uric acid. hypoxanthine –> xanthine (xanthine oxidase). guanine -> xanthine through deamination. xanthine -> uric acid through xanthine oxidase
pyrimidine degradation
gives B alanine and B aminoisobutyrate. undergo dephosphorylation, separation of base from ribose, deamination, and degradation of base
Gout
precipitation of sodium urate crystals in joints and kidneys. can be caused by PRPP synthase being abnormal and not responding to inhibition. Allopurinol treats it by blocking uric acid production
lesch-nyhan syndrome
x linked condition due to deficiency of HGPRT. increaed purine synth, increased PRPP with decreased IMP and GMP. symptoms are gout, urinary stones, brain problems. treat with allopurinol
adenosine deaminase deficiency
high levels of dATP inhibit DNA synth, causing white blood cells to not proliferate. associated with SCID. bone marrow transplant and enzyme replacement are treatments
