Urea cycle

Question 0

Glutamate dehydrogenase

Answer 0

reductive amination of alpha-ketoglutarate

alpha-ketoglutarate to L-glutamate and produces NAD(P)

Question 1

Ammonia metabolism in Hepatocytes

Answer 1

Periportal hepatocytes - High capacity, low affinity
Perivenous hepatocytes - low capacity, high affinity (glutamine synthetase detoxes NH3, incorporates NH3 into glutamine)
glutamine is a nitrogen carrier

Question 2

Glutamine synthetase

Answer 2

glutamate + NH4 converted to Glutamine

produces ADP

Question 3

Glutamate role in ammonia transport

Answer 3

hands off NH3 to alanine

in the liver, it hands off NH3 for incorporation into urea

Question 4

synthesis of Nitric oxide (NO) from arginine

Answer 4

NO is a gas hormone
diffuses rapidly into cells
activates cGMP synthesis and relaxes blood vessels and lowers BP
neurotransmitter in brain - high levels during stroke kill neurons
Nitroglycerin converted to NO and dilates coronary arteries in treating angina pectoris

Question 5

Fate of ammonia: 3 major reactions in all cells

Answer 5

Glutamate dehydrogenase - reductive amination of alpha-ketoglutarate to form glutamate
Glutamine synthetase - ATP dep. amidation of y-carboxyl of glutamate to glutamine
Carbamoyl phosphate synthetase I - two ATP required, one to activate bicarb and one to phosphorylate carbamate

Question 6

At physiologic pH equilibrium favors NH4+ by a factor of

Answer 6

100/1

Question 7

NH3 can cross membranes

Answer 7

passes into urine from kidney tubules cells and decreases acidity of urine by binding protons and forms NH4+ which cannot cross membranes

Question 8

Transamination

Answer 8

is the transfer of an amino group from an alpha amino acid to alpha keto acid

Question 9

serine can make

Answer 9

cysteine

Question 10

Glycine and ____ are interconvertible

Answer 10

serine

Question 11

Glucogenic Amino acids

Answer 11

Ala, ser, cys, gly, thr, trp = pyruvate 
asp, arg = OAA 
Ile, Met, Val = succinyl CoA 
Asp, Phe, Tyr = fumarate 
Arg, Gln, Glu, Pro, His = alpha ketoglutarate

Question 12

Ketogenic amino acids

Answer 12

Leu, Lys, Phe, Tyr = acetoacetate
Ile, Leu, Thr, Trp = acetyl CoA
Only ketogenic = Leu and Lys

Question 13

Breakdown of branched chain amino acids

Answer 13

Leucine, valine and Isoleucine
broken down to acetoacetate and acetyl CoA
via HMG-CoA which is an intermediate in CH and KB

Question 14

Transamination reaction

Answer 14

done via PLP = pyridoxal phosphate, cofactor B6

Aspartate and alpha-ketoglutarate to OAA and glutamate

Question 15

Glucose-Alanine cycle

Answer 15

shuttles NH3 from muscle to liver via Alanine which is converted back to pyruvate then to glucose
pyruvate is alanine plus amino group

Question 16

Glutamine

Answer 16

synthesized in peripheral tissues from glutamate and NH3
glutamine is shuttled to liver where the NH3 is removed (glutamate) and another is removed (alpha-ketoglutarate) both NH3 and added to Urea

Question 17

What happens to protein in the FED state?

Answer 17

AA has CO2 removed

incorporated in protein or TAG or Glucose or shuttled to cells

Question 18

what happens to amino acids in the FASTING state?

Answer 18

protein is broken down into AA
goes through the TCA cycle to glutamine where in peripheral tissues converted back to alanine or allows carriage of NH3 to kidneys for excretion
or Alanine from breakdown to liver for KB and Glucose and excess NH3 to urea

Question 19

how does OAA contribute NH3 to the urea cycle?

Answer 19

reacts with glutamate to generate alpha-ketoglutarate and aspartate
Aspartate combines with citrulline to start the cycle in the cytoplasm

Question 20

what does glutamate do?

Answer 20

collects NH3 from AA through transamination to deliver it to Aspartate

Question 21

Components of urea cycle

Answer 21

NH3 and Co2 combine to make carbamoyl phosphate
this reacts with ornithine to make citrulline
Citrulline exits the mitochondria
citrulline and aspartate combine (uses ATP to AMP) to make argininosuccinate which splits into Fumarate and Arginine
Arginine back to Ornithine in the mitochondria gives off NH3 which is combined with H20 to make Urea

Question 22

NH4+ and bicarb and ATP =

Answer 22

Carbamoyl phosphate
requires 2 ATP
catalyzed by carbamoyl phosphate synthetase I
this in the liver and intestines

Question 23

Carbamoyl phosphate and ornithine =

Answer 23

citrulline

crosses out of mito and into cytosol

Question 24

citrulline and aspartate =

Answer 24

make argininosuccinate

Question 25

Argininosuccinate

Answer 25

splits to Arginine and Fumarate

Question 26

Arginine in the urea cycle

Answer 26

which is just NH4 and aspartate splits to urea and ornithine ornithine is exchanged with citrulline

Question 27

Regulation of Urea cycle

Answer 27

higher ammonia leads to more urea production feed forward regulation 1. allosteric activation of CPSI by NAG 2. induction/repression of synthesis of urea cycle enzymes NAG is made from acetyl CoA and glutamate Arginine stimulates the cycle prolonged fasting or protein degradation increases the cycle

Question 28

Urea cycle defects can cause

Answer 28

``` feeding difficulty vomiting lethargy irritability tachypnea convulsive crisis acute encephalophaty coma when serum over 300umol/L ```

Question 29

how would treat urea cycle defect?

Answer 29

L-arginine and L-carnitine sodium benzoate and sodium phenylbutarate Long term - low protein diet, liver transplant and dialysis

Question 30

Hyperammonia

Answer 30

150 ulmol/L neonates | 80 ulmol/L adult and children

Question 31

Disorder of the urea cycle

Answer 31

ammonia can accumulate - toxic to nervous system free NH3 rapidly fixed to a-ketoglutarate to glutamate to pyruvate which makes Alanine and is transported to the liver see elevated glutamine as well

Question 32

what aids Nitrogen removal from the body?

Answer 32

Benzoic acid and Phenylbutyrate Benzoic + glycine makes Hippuric acid and the body must make serine to replace lost glycine Phenylbutyrate + glutamine = conjugate is excreted Body uses glucose and 2 nitrogens to remake glutamine

Question 33

2 alanine =

Answer 33

1 glucose

Question 34

2 nitrogen =

Answer 34

1 Urea

Question 35

Urea cycle during fasting

Answer 35

liver maintains glucose muscle is major carbon source excretion of urea is high eventually less muscle protein used and urea decreases Brain switches to KB

Question 36

Glucagon release during fasting stimulates

Answer 36

alanine transport to the liver