aa oxidation & urea cycle

eating types and energy

obligate carnivores get over 90% of their energy from protein, omnivores get 10-20%

protein digestion

1. enter stomach, which stimulates release of gastrin

2. gastrin simulates release of hcl

3. hcl dec ph, which activates pepsinogen by cleaving it

4. pepsinogen cleaved yields pepsin, which cleaves long pp’s into smaller fragments

5. the smeller frag enter intestine and causes pancreas to release bicarbonate (inc ph)

6. pancreatic proteases released into intestine and activated via proteolytic cleavage

7. these break pp into aa to be absorbed into intestine cells - any nonabsorbed aa/proteins are excreted as waste

what are 2 classifications of C skeleton in aa

glucogenic - can enter gng as tca intmd and be converted into glucose

ketogenic - broken down into acetylcoa or acetoacetate, precursors for ketone bodies

some can do both and it just depends on what enzymes get to them first - don’t need to memorize which aa go where

glucogenic aa

inc [oaa] (needed for gng) so C skeleton of aa → oaa, pyruvate, or tca intmd easily, its glucogenic

inc oaa pop w/o directly changing tca

aa → pyruvate, alpha ketogluterate, succinyl coa, fumarate, or oaa

ketogenic aa

aa that can form acetyl coa - specifically ile, val, and leu bc they’re branch chains

generate acetyl coa, and acetoacetylcoa to replenish tca but no direct inc in oaa just running cycle more efficiently

aa to pyruvate

don’t need to know mech but common first step: put NH3 from aa onto alpha ketogluterate to make glutamate and cont converting aa from there w/o the NH3

ile and val → succinyl coa, leu → acetyl coa and acetoacetate

what does converting aa do

takes off an NH2 / NH3w

what is done with the NH3 / NH2

enter urea cycle

done bc ammonia is v toxic and can build upw

how do diff species deal with ammonia

dept on how aq their environ is

fish - diffuse straight from body, nh3 is directly diluted bc of highly aq environ

mammals - make ammonia bc removes 2N removed in 1 molec and urea isn’t as toxic but still needs to be diluted

birds / reptiles - make uric acid, requires lses water and results in paste-like waste, gets rid of 4 N groups

basic removal step of amino groups

in the liver cells, transaminases / amiotransferases remove the NH3 group and put it onto an alpha-ketoglutarate, creating a glutamate (ex-glutamate) and keto acid (ex-aa)

glutamate can be converted back into alpha ketoglutarate by glutamate dehydrogenase, generating NADH and NH4+

requires PLP (vitamin b6) as a cofactor

how is the glutamate dealt with

free ammonia (NH4+) is incorporated into the glutamate by glutamine synthetase to make glutamine

gln moves through the bloodstream to the liver - form of transportation of N groups in non-toxic form

in mt of liver cells, glutaminase converts the glutamine into glutamate and releases the NH$+

COSTS 1 ATP

in general, what’s the rule about glu vs gln

in cells, its glu but while moving, its gln

what’s different for muscle cells

muscles cells do the previously mentioned method as well but when used vigorously, they max glycolysis, resulting excess pyruvate that can’t be oxidized bc of lack of O2 - only some pyruvate goes to lactic acid

also short on ATP so they break down aa, generating N waste

how do muscle cells dispose of amino groups in aa and recycle pyruvate

1. free NH4+ all gets put onto aa to make glutamate (previous pathway)

2. put NH4+ onto pyruvate → ala

3. both glutamate and ala go to liver safely

4. when ala arrives, it dets deaminated and the NH4+ is put on glu and goes into urea - turns ex-ala into pyruvate which gets put into gng and sent into bloodstream

ala to pyruvate

done via an aminotransferase with PLP as cofactor

also converts alpha ketoglutarate into glutamate

urea cycle

takes place in liver mt mostly

urea cycle prep

1. gln (glutamine) imported into the mt and → glu via glutaminase, releasing NH4+ (NH4+ and glu/gln from flashcard 11)

   1. OR it enters as glutamate from ala or aa oxidation

2. glutamate → alpha-ketoglutarate via glutamate dehydr, produces NH4+ and NAD(P)H

   1. OR asp aminotransferase takes the NH3+ and turns oaa → asp

3. 2 ATP + bicarbonate + NH4+ → carbamoyl phosphate

after prep pjase of urea, where does everything end up

all N from food / tissues converted into NH4+ or onto asp, all glu made into alpha-ketoglutarate

NH4+ to carbamoyl-P

done via carbamoyl phosphate synthetase i

N capturing reaction

uses 2ATP

need to know mech

urea cycle summary

1. carbamoyl phosphate → citrulline (mt → cytosol)

2. citrulline → argininosuccinate

3. argininosuccinate → arg and fumarate

4. arg → ornithine + urea (cytosol → mt)

fumarate → tca

urea water soluble, non-toxic, moves to kidneys for removal

rxn 1 of urea cycle

carbamoyl phosphate + ornithine to citrulline via ornithine transcarbamoylase

citrulline leaves mt to go to the cytosol

rxn 2 of urea cycle

citrulline + AMP + asp from prep phase → argininosuccinate + amp via argininosuccinate synthetase

AMP comes from ATP and releases 2(Pi)

asp comes from the glu to alpha ketoglutarate via asp aminotransferase

rxn 3 of urea cycle

arginosuccinate → arginine + fumarate via argininosuccinase

fumarate goes into tca and arg cont

rxn 4 of urea cycle

arg + h2o → ornithine + urea via arginase

urea moves to kidneys

ornithine omves back into mt

what are the 4 aa that play key roles in N metabolism

glu, gln, ala, asp

all 4 can easily be converted into tca intmd

glu/gln → alpha ketoglutarate

ala → pyruvate

asp → oaa

energetics of urea cycle

cost is high - 2ATP to activate carbamoyl-P and 2 to gen arginosuccinate (bc AMP used, means lost 2P)

fumarate goes into tca → oaa, making NADH

NADH → etc → 2.5ATP

basically covers the cycle but not by much