CMB Exam 2 - Details Flashcards
Lewis acid
e- acceptor (ie any ion/molecule that can accept a pair of nonbonding valence electrons). eg CO2
Why/how is there such a big discrepancy between H+ and HCO3- levels?
We need the excess HCO3- buffer for pH and to accomodate the continuous production of organic acids. Discrepancy established by kidney actively excreting H+ and actively reabsorbing HCO3-.
How does the body monitor blood pH?
Chemoreceptors in the carotid are sensitive to pO2, pCO2 and/or pH
respiratory compensation
In the case of acidosis, resp. rate increases to breathe off more CO2. In the case of alkalosis, resp. rate decreases.
anion gap
~12 ± 4 mEq/L = the quantity of anions in the serum (mostly HCO3- and Cl-) not balanced by cations (mostly Na+). Plasma is electro-neutral, so the “gap” of is actually balanced by negatively charged proteins. Exogenous acid increases the gap.
Derive the equation for the pH of blood.
What is normal arterial [HCO3-]?
~24 mEq/L HCO3-
What is normal arterial pCO2?
~35-45 mmHg CO2
Why is fructose more “evil” than glucose?
In the liver, since it can’t enter PP pathway or glycogen synthesis it’s preferentially converted to F1P to FA to TG to VLDL, bypassing glucokinase and PFK-1 (which are important regulators). This can also lead to deficiencies in aldolase B, causeing accumulation of F1P. Can rapidly deplete liver ATP/Pi levels and increase uric acid production (gout, hypertension).
normal fasting glucose levels
80-140 mg/dL (centered around 110 mg/dL)
Which enzymes are activated by glucagon? What are the results of this change?
Activation of: PKA, F-2,6 bisphoshatase, phosphorylase kinase, glycoden phosphorylase, hormone-sensitive lipase. This results in activation of gluconeogenesis and glycogenolysis.
Which enzymes’ activity is inhibited by glucagon? What are the results of the changes?
Inhibition of: PFK-2, PFK-1 indirectly, pyruvate kinase, glycogen synthase. Results in inhibition of glycolysis and glycogen synthesis.
What are the major gluconeogenic substrates?
Lactate, glycerol, and amino acids (except leu and lys). NEVER acetyl-CoA fatty acids.
“limit dextrin”
Glycogen with the 4-residue branch
acid maltase
Degrades glycogen in the lysosomes.
What are the three main categories of glycogen storage diseases?
Hepatic, myopathic, or “miscellaneous”.
How can insulin resistance directly increase blood glucose?
Lower insulin sensitivity causes lipolysis and increases fatty acid oxidation, which will decrease glucose utilization in the muscle and increase gluconeogenesis in the liver.
adiponectin
Activates AMPK, which appears to enhance insulin sensitivity; is anti-inflammatory; improves clearance of FFA, glucose and TG; suppresses gluconeogenesis
AMPK
Activated says LIVER: Increases glycolysis and decreases gluconeogenesis in the liver; MUSCLE: increasing FFA uptake, β-oxidation, and glucose uptake in the muscle.
What happens to glucagon levels as DM-2 progresses?
Glucagon response decreases as DM-2 progresses (meaning that instead of responding, it stays high).
Why can’t glucometers be used in diagnostics for glucose disregulation?
Glucometers have high variability at high glucose levels, so they are NEVER used for diagnosis
When can a random blood glucose test be diagnostic for diabetes?
When it’s over 200mg/dL AND the patient shows Si/Sx.
HbA1C
Diagnostic for diabetes when >6.5%
isomers
Two molecules with the same chemical formula but different arrangement of bonds/atoms.
epimers
Two molecules that are identical but differ at one stereocenter.
enantiomers
Two epimers that are mirror (non-superimposable) images of each other, aka “optic isomers” because they bend light differently. The D moieties are biologically relevant.
What is the difference between L and D carbohydrates? Which is biologically relevant?
They’re enantiomers (optical isomers).
anomers
Cyclical sugar molecules that are identical but differ at the anomeric carbon (C1) in the orientation of the groups.
What is the difference between α- and β-sugars?
They’re anomers; α has the axial group, β has the equitorial group.
What is the half life of hemoglobin?
6 weeks
pyranoses
6 member ring common to sugars; loosely resembles a pyran molecule
furanose
5 member ring common to sugars; loosely resembles a furan molecule
Maillard reaction
Refers to the glycation/fructation of free amino groups of proteins like hemoglobin; leads to production of AGEs.
Why is sucrose more stable than lactose?
In sucrose the reducing end of the carbons is tied up in the O-glycosidic bond, making it less reactive. Lactose has a reducing end free, so it’s susceptible to oxidation.
amylose
Long, unbranched D-glucose (α1,4) starch.
amylopectin
Highly branched D-glucose (α 1,4 & 1,6) starch.
glycogen
Very highly branched form of D-glucose. Starch.
dextrans
Branched starch from bacteria & yeast; componet of dental plaques.
cellulose
Unbranched starch with β1,4 bonds, making it impossible for our amylases to break them down.
glycosaminoglycans
Group of heteropolysaccharides that are important components of the extracellular matrix (eg collagens, elastins, fibronectin). All have STRUCTURAL importance.
hyaluronan
Glycosaminoglycan; forms viscous solutions for lubricants in synovial fluid of joints and vitreous humor of the eye; component of cartilage and tendons; LONGEST glycosaminoglycan
chondroitin sulfate
Glycosaminoglycan; covalently bound part of proteoglycans; contributes to tensile strength of connective tissue (eg wall of aorta)
keratan sulfate
Glycosaminoglycan; present in cornea, cartilage, bone, and dead cell stuff (hair, horns, hofs, nails, claws, etc.)
heparan sulfate
Glycosaminoglycan; produced by all animal cells; high degree of sulfation allows it to interact with many proteins (eg growth factors, enxymes, etc.)
proteoglycans
Major component of ECM. Glycosaminoglycans bound to membrane or secreted protein. Often longer, unbranched carb chains.
glycoproteins
Have 2 major functions: can be receptors (sugars give specificity) or enzymes (sugars protect from the environment). Sugars can also serve as a signal for breakdown. Often shorter, branched carb chains.
glycosphingolipids
Specialized lipids modified by oligosaccharides. Abundant in brain and stuff.
homopolysaccharides
Branching or non-branching chains of like monosaccharides with NUTRITIONAL function.
heteropolysaccharides
Branching or non-branching chains of various monosaccharides with STRUCTURAL function.
Where is most of the cell’s NAD+/NADH located?
~90% in mitochondria
Where is most of the cell’s NADP+/NADPH located?
Mostly in the cytosol (to maintain a reductive environment).
In a healthy cell, what is the ratio of NAD+ to NADH? Why?
NAD+ >> NADH. If NADH accumulates it probably means that ATP production is low.
In a healthy cell, what is the ratio of NADP+ to NADPH? Why?
NADP+/NADPH = 0.05. The major role of NADP is to maintain a reductive environment in the cytosol to protect proteins etc.
α-amylase: what is it, where is it produced?
An endoglycosidase specific for α-1,4 bonds. Present in saliva but mostly in the duodenum.
What are the monosaccharide components of sucrose?
Glucose and fructose.
What are the monosaccharide components of lactose?
Glucose and galactose.
Other than the site of action, what is the big difference between endoclycosidases and exoglycosidases?
Endoglycosidases are secreted (and thus need to be replaced) whereas exoglycosidases are anchored into the villi.
GLUT4 - what is it and where is it?
The only insulin-dependent glucose transporter (UNIPORT); present in adipocytes, cardiac and skeletal muscle.
GLUT2 - what is it and where is it?
NOT insulin dependent; allows glucose, fructose and galactose to follow the gradient. “Senses” blood glucose levels (high KM for glucose). Present in the pancreas and liver, as well as most enterocytes.
GLUT5
Fructose uniport into enterocytes, cells of proximal tubules.
SGLT1
Sodium glucose symporter. Needs Na+ gradient.
GLUT1
Ubiquitous glucose and galactose transporter (gradient).
GLUT3
Glucose and galactose uniport into brain, placenta, testes.
What tissues are insulin dependent? Which are insulin independent?
DEPENDENT: Muscle, fat (liver too, but not for energy). INDEPENDENT: brain, RBCs
glycolysis - what’s the purpose (and where)? net result?
LIVER: does glycolysis to turn free glucose into triglycerides (in the fed state), exporting them as VLDL. ADIPOCYTES: use glycolysis for glycerol-3-P synthesis (in the fed state). OTHER TISSUES: use glycolysis for energy; RGC & brain always; muscle un demand (regardless of fed/fast state).
hexokinase (what does it do, and in which tissues is it present)
Phosporylates hexoses (including glucose) nonspecifically and unidirectionally. Requires ATP hydrolysis. Present in RBCs, muscle, and fat (and most tissues other than the liver and pancreas). Inhibited by glucose-6-phosphate (product inhibition). Expression NOT regulated by insulin.
glucokinase (what does it do, and in which tissues is it present)
Unidirectionally phosphorylates glucose (ATP hydrolysis!), forming glucose-6-phosphate (removing it from glc pool). In the pancreas, it “measures” rate of glucose intake to regulate insulin release. Most common in LIVER and PANCREAS. Secuestered to nucleus by GKRP in the presence of F6P (fasted state), released from GKRP in the presence of F6P (fed state).
phosphohexose isomerase
Converts glucose-6-phosphate to fructose-6-phosphate (and vice versa).
PFK-1
(phosphofructokinase-1) Phosphorylates (ATP hydrolysis!) fructose-6-phosphate to fructose-1,6-bisphosphate. Inhibited by ATP always. LIVER: Activated by F-2,6-BP (product of PFK-2). MUSCLE/RBCs: activated by AMP.
aldolase
Splits fructose-1,6-bisphosphate into 2 molecules: glyceraldehyde-3-phosphate and dihydroacetone phosphate.
triosephosphate isomerase
Converts dihydroxyacetone phosphate (the other product of fructose-1,6 catabolism) to glyceraldehyde-3-phosphate. (Side note: in adipose tissue, this generates NAD+?)
glyceraldehyde-3-phosphate dehydrogenase
Oxidizes glyceraldehyde-3-phosphate to 1,3-bisphosphoglycerate, generating NADH.
What do dehydrogenases do?
In general, they oxidize a molecule (strip a hydride) and reduce a carrier like NAD+ to NADH.
phosphoglycerate kinase
Dephosphorylates 1,3-phosphoglycerate, generating 3-phosphoglycerate and ATP.
phosphoglycerate mutase
Moves the phosphate on 3-phosphoglycerate to the 2- position.
enolase
Pulls a water molecule out of 2-phosphoglycerate forming phosphoenolpyruvate.
pyruvate kinase
Dephosphorylates phosphoenolpyruvate, forming pyruvate and ATP. Regulates glycolysis (hormones). Activated by F16BP, in the liver it can be activated via dephosphorylation. Inhibited by ATP or in the liver by phosphorylation by PKA.
lactate dehydrogenase
In anaerobic conditions, converts pyruvate to lactate to regenarate NAD+.
2,3-bisphosphoglycerate in RBCs
A small portion of 1,3-bisphosphoglycerate is transfered to 2,3-BPG instead of 3-phosphoglycerate; this way the cell misses out on an ATP molecule, but the 2,3-BPG is important to regulate O2 affinity of Hb.
What’s different between the binding curves of glucokinase vs hexokinase?
Hexokinase reaches Vmax almost immediately (hyperbolic curve). The glucokinase curve is sigmoidal and has a Km 100x higher. As the concentration of gllucose increases, so does the velocity. This is how the pancreas keeps insulin release proportional glucose concentration.
GKRP
(Glucokinase regulatory protein) sequesters glucokinase to the nucleus in the presence of F6P (ie fasted state); dissociates in the presence of F1P (fed state).
PFK-2
(phosphofructokinase-2) A small proportion of F6P is phosphorylated by PFK-2 to form F-2,6-BP, which is absolutely necessary for PFK-1 to become active. PFK-2 is inhibited (via PKA) as a consequence of glucagon action, which also inhibits both fructose-1,6-bisphosphatase (gluconeogenesis) and PFK-1 (glycolysis) and activates phosphorylase (glycogen degradation). In this phosphorylated state, PFK-2 loses it’s kinase activity and the other side of the enzyme acquires F-2,6-bisphosphatase activity to degrade F-2,6-BP (to allow gluconeogenesis). Also activated by AMP in RBCs/muscle/brain.
F-2,6-BP
Product of phosphorylation of F6P by PFK-2. Absolutely necessary for PFK-1 activation in LIVER. It also inhibits fructose-1,6-bisphosphatase, inhibiting gluconeogenesis.
glycogenin
Glycogen synthesis primer: self-glucosylating homodimer, each attaches glu from UDP-glu to a tyrosine residue on the other monomer and they get pushed apart as they grow.
phosphoglucomutase
Turns Glu1P (from glycogenolysis) to Glu6P for glycolysis
glucose-6-phosphatase
IN THE LIVER (membrane bound in the ER), dephosphorylates Glu6P so glucose can be released into the blood. Deficiency leads to von Gierke disease (type Ia glycogenosis).
Which reactions in glycolysis are irreversible?
Glucokinase, PFK-1, and pyruvate kinase reactions are all highly exergonic.
Where in the cell does gluconeogenesis occur?
Mostly in the cytosol (some precursors are generated in the mitochondria)
Name the 4 kinds of gluconeogenic substrates.
Lactate (produced by RBCs and muscle from pyruvate), amino acids (except leucine and lysine), glycerol, and all of the TCA intermediates (which does not include acetyl-CoA).
phosphohexomutase
Turns Glu6P to Fru6P and vice versa.
fructose-1,6-bisphosphatase
Dephosphorylates F-1,6-P to F6P in gluconeogenesis.
What are the effects of ethanol in gluconeogenesis?
The metabolism of ethanol uses up all the NAD+ in the cytosol, inhibiting gluconeogenesis (lactate dehydrogenase and malate dehydrogenase both need NAD+). This is especially for pre-teens and young adults who can’t process it as well.
What family of metabolic enzymes requires biotin (Vit B7)?
Carboxylases.
What are the potential causes of biotin deficiency?
Defective enzymes (either that attach it to the carboxylases or the biotinidase that detaches it), mal absorption (eg too much avidin in diet), excessive drinking, smoking, or antibiotic treatment.
What is the purpose of the pentose phosphate pathway?
To provide 2 things: NADPH (for reductive biosynthetic pathways, maintaining the cytosolic reductive environment via glutathione) and/or ribose-5-phosphate (for nucleotide synthesis). If only NADPH is needed then the ribose-5-P is recycled to G-6-P to repeat PPP.
xylulose-5-P
An important activator of protein phosphatases in the liver, speeding the reversal of glucagon activity.
superoxide in RBCs
Produced spontaneously in RBCs: ~1% of O2 oxidizes Hb-Fe2+ to Hb-3+, and the O2- can combine with water to form H2O2. These ROS denature hemoglobin (Heinz bodies) and damage cell membranes, leading to cell lysis and hemolytic anemia.
Heinz bodies
Denatured hemoglobin precipitates, resulting from ROS in blood cells.
hemolytic anemia
RBC lysis from Heinz bodies and cell membrane damage as a result of ROS.
glutathione
Tripeptide (synthesized by enzyme, NOT RIBOSOMES!) with a central cysteine residue that can be oxidized to form a homodimer. Monomers are substrate for glutathione peroxidase and are used to reduce oxidized Hb (ie Hb with disulfide bonds). The monomers are regenerated by glutathione reductase, which uses NADPH to reduce the glutathione dimer back to monomers.
glutathione peroxidase
Uses to molecules of glutathione to repair oxidative damage (eg Heinz bodies), leaving a glutathione dimer.
glutathione reductase
Regenerates glutathione monomers by reducing the homodimer that forms after glutathione peroxidase uses them to repair oxidative damage.
List the cofactors necessary for the pyruvate dehydrogenase complex.
TPP (vit B1), lipoic acids, FAD (riboflavin, vit B2), NAD+ (niacin, vit B3), CoA (pantothenic acid, vit B5).
E1 subunit of PDH
This is the actual pyruvate dehydrogenase component. Comprises 20-30 subunits.
E2 subunit of PDH
This is the dihydrolipoyl transacetylase component. Comprises 60 subunits.
E3 subunit of PDH
This is the dihydrolipoyl dehydrogenase component. Comprises 6 subunits.
What is the major role of the TCA cycle?
In most cells: produce NADH from acetyl-CoA. In the liver: use excess energy for biosynthesis of fatty acids (TCA rarely goes past citrate in the liver).
What are the overall net products and reactants of the TCA cycle?
Acetyl CoA + 3 NAD + FAD + GDP + Pi —-> HS-CoA + 2 CO2 + 3 NADH + FADH2 + GTP
What would happen the the level of acetyl-CoA in the liver if all the OAA is busy (gluconeogenesis)?
Acetyl-CoA would accumulate in the liver if there’s not enough OAA because it needs OAA to run in the TCA cycle. The liver will have to turn acetyl-CoA into ketone bodies.
What is the importance of citrate in the liver?
In the liver, the TCA cycle stops after acetyl-CoA is added to OAA forming citrate. Citrate is then exported from the mitochondria to the cytoplasm to be reconverted to acetyl-CoA. Ultimately important for fatty acid biosynthesis.
pyruvate carboxylase
In the fed state, can convert a portion of pyruvate to oxaloacetate to avoid the accumulation of acetyl-CoA.
PEP carboxykinase
Converts PEP to OAA (esp in heart and skeletal muscle) to prime TCA.
Pasteur effect
Refers to the fact that glycolysis decreases in the presence of O2 because TCA and electron transport chain produce energy more efficiently.
ubiquinone (coenzyme Q)
e- acceptor in the e- transport chain. Contains a hydrophobic isoprene side chain whose synthesis happens to be inhibited by statins.
cytochromes
Red or brown heme proteins with iron (Fe3+) or copper one-electron carriers. All (EXCEPT CYTOCHROME C!) are integral membrane proteins. Cytochrome C is water soluble. A and B hemes are held in a cage, whereas C hemes are covalently bound to C cytochromes.
nicotinamide nucleotide transhydrogenase
In the mitochondria, turns a small portion of NADH into NADPH for the purpose of regenerating reduced glutathione.
What does it mean to “uncouple” oxidative phosphorylation?
Inhibit ATP synthesis (and increase heat production) but have no effect on electron transport or oxygen consumption. They “smuggle” protons back across the inner mitochondrial membrane after they’ve been pumped in the ETC.
perilipin
Protein that coats lipid storage droplets. Is phosphorylated by PKA causing it to open up and give HSL access to the triacylglycerol inside.
hormone-sensitive lipase (HSL)
Activated when glucagon causes cAMP rise in cells and PKA phophorylates HSL. HSL releases the first of the three FFA from TG. HSL is inactivated when insulin causes phosphodiesterase to remove cAMP and lipase phosphatase to dephosphorylate HSL.
carnitine-palmitoyl acyltransferase (CPT)
Facilitates transport of FFAs from the cytosol through the membrane and the space into the mitochondrial matrix, with the help of carnitine. Can be inhibited by accumulation of malonyl-CoA.
What are the 4 levels of lipid metabolism that are regulated?
1) lipolysis, 2) FFA entry into mitochondria (malonyl-CoA inhibits carnitine-palmitoyl acetyltransferase), 3) availability of coenzymes for β-oxidation (eg alcohol uses up NAD+), and 4) glycerogenesis (FFA recycling).
ACP
(acyl carrier protein) An analog of CoA that is the carrier of acyl molecules during energy degradative metabolism. During FA synthesis, it binds malonyl CoA to help it continue the FA synthesis process.
citrate lyase
Under insulin activation, converts cytosolic citrate into acetyl-CoA for FA synthesis.
malonyl-CoA
The substrate used by FA synthase. Produced from acetyl-CoA by acetyl-CoA carboxylase under insulin activity. Accumulation of malonyl-CoA can inhibit CPTI to limit further breakdown of FAs.
Why are some FAs resynthesized into TGs after release?
It appears to be the body’s way to limit FA release to avoid toxic accumulation of FA.
lipoprotein lipase
Breaks down the fat in VLDL or chylomicrons, facilitates the release of FA from lipoprotein into the target (fat or muscle tissue).
glycerol kinase
Present only in the liver, allows liver to turn glycerol to glycerol-3-phosphate which is necessary in the process of TG synthesis. Does NOT need insulin for this process.
adenine vs adenosine
Adenine is the nitrogenous base, adenosine is the ribonucleotide with the sugar and phosphate added on.
Where does purine synthesis mostly occur?
In the liver.
inosine monophosphate (IMP)
Formed as the product of 9 steps of metabolism of ribose-5-phosphate in the synthesis of purines.
IMP dehydrogenase
Turns IMP into xanthosine monophosphate, which can then be converted to GMP. Inhibited by mycphenolic acid.
adenylosuccinate synthetase
Turns IMP into adenylosuccinate, which is then converted into AMP.
adenylate kinase
Converts AMP +ATP —-> 2 ADP
guanylate kinase
Converts GMP + ATP —-> GDP + ADP
nucleoside diphosphate kinases
Nonspecifically convert NDPs to NTPs using ATP.
CPSI vs CPS II
CPSI is in mitochondria for the urea cycle (uses ammonia) and is activated by N-acetyl-glutamate. CPSII is in the cytosol for pyrimidine synthesis (uses glutamine) and is activated by ATP but inhibited by UTP.
What is the product of cytidine degradation?
β-alanine
What is the product of 2-deoxythymidine degradation?
β-aminoisobutyrate
How are ribonucleosides converted to deoxyribonucleosides? (what enzyme)
Ribonucleotide reductase* uses NADPH to reduce a ribonucleotide diphosphate to 2-deoxyribonucleoside. (Thymine has its own enzyme, thymidylate synthase, whuch methylates dUMP to dTMP)
How is the “T” deoxyribonucleotide synthesized? (what enzyme)
Thymidylate synthase* adds a methyl group to dUMP (uracil), making it dTMP (thymine)
Once the NH3 is removed from amino acids during degradation, what is the final fate of the nitrogen-free intermediate?
It can be turned to glucose, to ketone bodies, or broken down to CO2 and H2O.
Describe the normal adult amino acid pool equilibrium.
Our pool of AAs fed by the diet (~100g/day) and an equilibrium exists between the AA pool and the body protein pool (~250-300g/day). AAs can also be degraded (~100g/day) to ammonia and nitrogen-free intermediates.
How does pregnancy affect the AA pool equilibrium?
Increase in dietary protein to synthesize more body protein.
How does protein deficiency affect the AA pool equilibrium?
Less comes in so less can go to make protein, even though it’s getting broken down at the same rate.
How does essential AA deficiency affect the AA pool equilibrium?
Lots of protein can come into the AA pool but little can be used for body protein, so there’s an increase in urea production.
How do wasting disease, burns, and trauma affect the AA pool equilibrium?
Lots of body protein is broken down into the AA pool, so there’s excess of urea production as well.
Which amino acids can be synthesized by humans?
Ala, Asp, Asn, Glu, Ser
Which amino acids are “conditionally” essential (can be synthesized only at some stages)?
Arg, Cys, Gln, Gly, Pro, Tyr
Which amino acids can never be synthesized by humans?
His, Iso, Leu, Lys, Met, Phe, Thr, Try, Val
How are the “other” amino acids (not the main 20) synthesized
Post-translational modification of AAs in protein.
Which are “stabilizing” N-terminal AAs?
Met, Ser, Gly, Ala, Thr, Val
Which are “destabilizing” N-terminal AAs?
Arg, Lys, Leu, Phe, Asp, Tyr
What is the PEST sequence?
A protein turnover sequence: Pro Glu Ser Thr.
What are the differences between lysosomal and proteosomal degradation?
LYSOSOMAL: energy independent, primarily extracellular proteins. PROTEOSOMAL: energy-dependant, primarily internal proteins tagged via ubiquitin.
What are the sources of ammonia in the body?
Amino acids, glutamine, bactieral urease, dietary and endogenous amines, and nucleotide metabolism.
What enzymes release ammonia from amino acids?
Aminotransferase and glutamate dehydrogenase
What enzymes release ammonia from glutamine? Where in the body does this occur and what happens to the ammonia?
Renal glutaminase and glutamate dehydrogenase. This happens in the kidney, and the ammonia is excreted in the urine.
What bacterial enzyme releases ammonia? Where in the body does this occur and what happens to the ammonia?
Bacterial urease cleaves any urea that is leaked into the intestine. This is abosorbed in the small intestine via the portal vein and broken down in the liver, or else it is lost in feces.
What enzymes release ammonia from amines (like neurotransmitter monoamines)?
Amine oxidases
What are the two sources of urea nitrogen?
Ammonia and aspartate
pyridoxal phosphate
Coenzyme that is covalently linked to a lysine in the aminotransferase active site. Eg carries the NH3 from glutamate to OAA forming aspartate.
Other than transamination, what additional mechanisms of amino acid deamination exist?
Oxidative deamination (via oxidases that use FMN) and nonoxidative deamination of hydroxyamino acids (via dehydratases)
glutamate dehydrogenase (GDH)
GDH reduces α-ketoglutarate to glutamate and vice versa.
glutaminase
Breaks down the glutamine that tissues send to the liver into glutamate and NH3, which then enters the urea cycle.
What is a normal level of blood urea nitrogen?
250-700 uM/I.
carbamoyl phosphate
In the mitochondria, is the product of ammonium combination with HCO3- and cleavage of 2 ATP (via carbamoyl phosphate synthetase). It’s then combined with ornithine to form citrulline (via ornithine transcarbamoylase).
carbamoyl phosphate synthetase I
Catalyzes the combination of NH4+, HCO3-, and 2 ATP into carbamoyl phosphate. Deficiency leads to high blood ammonia and low everything else in the UC cycle.
ornithine
Is the product of the cleavage of urea from arginine in the cytosol. Is then imported into the mitochondrion to combine with carbamoyl phosphate (in exchange for H+ or
ornithine transcarbamoylase
Catalyzes the combination of ornithine and carbamoyl phosphate in the mitochondria. Deficiency leads to high ammonia, low arginine, low citrulline, and high orotate.
citrulline
Product of the combination of carbamoyl phosphate and ornithine (via ornithine transcarbamoylase) in the mitochondrion. Is exported from the mitochondrion to combine with aspartate to form argininosuccinate (via argininosuccinate synthetase).
aspartate’s role in the urea cycle
Combines with citrulline to form argininosuccinate (via argininosuccinate synthetase).
argininosuccinate synthetase
Catalyzes the formation of argininosuccinate from citrulline and aspartate (and ATP). Deficiency leads to high ammonia, low aarginine, high citrulline, and low orotate.
argininosuccinate
Formed in the urea cycle by argininosuccinate synthetase from aspartate and citrulline. Broken down into fumarate and arginine by argininosuccinate lyase.
fumarate
Component of both the TCA cycle and the urea cycle. In the urea cycle, produced by arginosuccinate lyase activity. Can be hydrated to malate and brought into the mitochondria through the malate shuttle and reenter the TCA cycle.
arginine (urea cycle)
Produced by arginosuccinate lyase activity. Broken down by arginase to urea and ornithine. Stimulates N-acetylglutamate synthase, which activates CPSI and initiates the urea cycle. Can be used to treat UCDs (except for arginase deficiencies).
argininosuccinate lyase
Catalyzes the breakdown of arginosuccinate into fumarate and arginine. Deficiency causes high ammonia, low arginine, MODERATE CITRULLINE, and low orotate.
arginase
Catalyzes the breakdown of arginine to urea and ornithine. Is ONLY expressed int he liver, so only liver can do the urea cycle. Deficiency leads to moderate ammonia in blood, high arginine, low citrulline, and low orotate.
carbamoyl phosphate synthetase II
Involved in pyrimidine synthesis. Not to be confused with CPSI, which is involved in the urea cycle.
What activates CPSI in the urea cycle?
N-acetylglutamate
Which is the rate limiting step of the urea cycle?
CPSI
