Proteins II Flashcards
Where does the urea cycle occur?
mitochondria and cytosol
Where does transition in urea cycle from mitochondria to cytosol occur?
Antiporter (ORNT1 and 2) transport ornithine in and citrulline out of mitochondria
What does carbomyl phosphate synthetase I do?
mitochondrial enzyme
combines HCO3- with NH3 to form carbomyl phosphate
Key regulated step in urea cycle
enzyme requires N-acetylglutamate for activation
What kick starts the urea cycle?
CPS-I (carbomyl phosphate synthetase I)
REQUIRES N-acetylglutamate for activation
What is used to transfer ammonia from peripheral tissue
glutamine
- to the kidneys where it is removed in the form of ammonia through urine
- to liver where it is removed in the form of urea (through blood to kidney)
What is used to transfer ammonia from muscle
alanine
Glutamate dehydrogenase
removes NH3 from glutamate to yield alpha-ketoglutarate and NH3 or vice versa
Liberates NH3 from glutamate or adds NH3 to form glutamate
Ubiquitous in liver/kidney/muscle/periphery
What dictates directionality of Glu Dehydrogenase?
relative concentration of Glu, alpha-ketoglu, NH3
Key regulatory point in protein catabolism
ATP GTP ADP GDP
Regulation of Glu dehydrogenase?
ATP and GTP are allosteric inhibitors… does this make intuitive sense? If we have lots of energy are we going to be anabolic or catabolic? Anabolic - we are building so we want to inhibit urea cycle
ADP and GDP are allosteric activators… does this make intuitive sense? If we are energy low, we are going to need to breakdown - catabolize –> urea cycle activation :)
Why is arginine significant in the urea cycle?
Well, in addition to it being an intermediate (precursor to the production of ornithine and urea via arginase) it can be complexed with glycine to yield creatine phosphate in muscles… which is important for energy
In addition to the interconversion of aspartate and oxaloacetate via transamination, aspartate can also be converted to ________ in the urea cycle which can then enter the Krebs cycle and be converted to?
Aspartate–>Fumerate –> Oxaloactate
Branched chain amino acids
leucine
isoleucine
Valine
MSUD
Genetic deficiency in branched chain alpha-keto acid dehydrogenase
leads to high concentration of branched chain keto acids (as they have already been deaminated) in urine adn gives a characteristic odor
TSH
Thyroid stimulating hormone?
stimulates iodide (I-) uptake
stimulates release of T4, T3
Thyroid peroxidase
Oxidizes iodide (I-) to I2
Thyroglobulin (Tg)
Big ass protein that contains Tyrosine residues that are to iodinated to form T4, T3
Thyroxin binding globulin (TBG)
Transports T4 and T3
Which form is more active T3 or T4?
T3
T3 and T4 are made from which aa
Tyrosine
Inherited defects in heme synthesis
Porphyrias
gamma-aminolevulinate synthase
gamma-ALA synthase
Enzyme regulating first step of heme production - the smooshing together of Glycine and Succinyl-CoA
also product (gamma-ALA) elevated in urine in tyrosinemia type I?
Which micronutrient is involved in heme synthesis?
Zinc
Gamma-ALA dehydratase in zince depedent
Lead is known to poison which synthetic pathway?
Lead poisoning –> anemia because it can replace zinc or iron in enzymes involved in heme synthesis
Zn in ALAdyhyratase
Fe in ferrochelatase
Heme inhibits? in Heme synthesis
Initial enzymes
ALA-S1
ALA-S2
Where does heme synthesis occur?
In mitochondria and cytoplasm
Heme degradation?
Heme–>Biliverdin–>Bilirubin–>Bilirubin-diglucuronide–>Stercobilin
Bilirubin is transported?
By albumin
High bilirubin–?
jaundice
Bilirubin is an?
anti-oxidant
Crigler Najjar syndrome
Defect in bilirubin glucuronyl-transferase
Gilbert syndrome
Defect in bilirubin glucuronyl transferase - less severe
Dubin Johnson syndrome
Defect in bilirubin transporter - secrete conjugated bilirubin into bile (to bile, MRP2)
What causes neonatal jaundice frequently?
low levels of bilirubin glucuronyl transferase - treat with fluorescent light which converts bilirubin to more polar products allowing removal similar to conjugated bilirubin
What are the two nitrogen contributors to the urea cycle?
Aspartate - comes from transamination reaction with Glutamate (AST)
NH4+ directly - comes from glutamate dehydrogenase (ALT generated glutamate from Alanine to yield pyruvate)
Tyrptophan metabolism results in the formation of
seratonin, melatonin, niacin
