Nitrogen & Nucleotide Metabolism Flashcards
What are the “goals” of the oxidative phase of the PPP?
Produce NADPH and 5 C sugars (ribulose-5-phosphate)
What is the “goal” of the nonoxidative phase of the PPP?
Convert pentose phosphates to glycolytic intermediates
What is the molecule that is partitioned between glucose and the PPP?
Glucose-6-Phosphate (goes into PPP if NADPH is needed, into glycolysis if ATP is needed)
What happens to NADPH made in the oxidative phase of the PPP?
It is used to support reductive biosynthesis (e.g. used for NAD+, FAD synthesis)
What are examples of tissues that might need NADPH?
Those synthesizing fatty acids, cholesterol, steroid hormones
What can be made from R-5-P?
Nucleotides, NAD+, FAD, CoA
Which molecule in the PPP is used for amino acid synthesis?
E4P; bacteria use to make aromatic AAs
Which nucleotide form is attached to ribose throughout its synthesis?
Purines
A Nucleoside
Adenosine
G Nucleoside
Guanosine
T Nucleoside
Thymidine
U Nucleoside
Uridine
C Nucleoside
Cytidine
What are the metabolic precursors for de novo synthesis of purines?
AAs, R5P, CO2, NH3
What is the committed step of purine synthesis?
Conversion of Glu to Gln
How does allopurinol work?
Prevents conversion of xanthine to uric acid (competes with hypoxanthine for access to xanthine oxidase)
Hydroxyurea molecular mechanism
Disrupts tyrosyl radical on RNR
How does muscle get the molecules that it needs?
- Own stored fuels
- Other organs
- Creatine Kinase Reaction
What is the fate of dietary glucose?
1/3 to liver glycogen, 1/2 of remainder to muscle glycogen, other 1/2 of remainder oxidized for immediate needs
What does glucokinase do?
Converts glucose to G6P, lower affinity for glucose than other hexokinases (high BG needed for binding)
Pathways for G6P in liver
- Back to glucose (blood glucose)
- Glycolysis
- ATP
- Acetyl CoA (FA synth)
- PPP
Pathways for lipids in liver
- TAG, PLs
- B Ox to Acetyl CoA (ATP, KBs, sterol synthesis)
- Heart & muscle for energy
Pathways for AAs in liver
- Proteins, other organs
- Precursors for proteins, nucleotides, hormones, etc.
- Pyruvate & ammonia:
- Ammonia –> Urea
- Pyruvate –> GNG
- Acetyl CoA
- CAC/OxPhos
*Lipid Storage
*GNG
Phosphocreatine Cycle
Phosphocreatine + ADP –> Creatine + ATP
How does the heart obtain its ATP?
Mostly from FA oxidation, glucose and KBs are other source
Cori Cycle
Glucose –> Pyruvate –> Lactate
(Reversed in liver) –> Glucose back to muscle
What are the three reasons that proteins would need to be degraded?
- Damaged
- Unnecessary
- Misfolded (DUM)
What molecule is used to test protein half-lives? How does it work?
Cyclohexylamine (CHX), inhibits translation)
Destabilizing N Terminal Residues
Leu, Lys, Asp, Arg, Phe (LLAAPS)
Stabilizing N Terminal Residues
Val, Met, Thr, Ala, Gly (VM TAGS)
PEST Proteins
Pro (P), Glu (E), Ser (S), Thr (T), quickly degraded
What are the two major degradation pathways?
- Endosome-Lysosomal Path (extracellular, endocytosis)
- Autophagy (intracellular)
Cathepsins
Proteases in the lysosome that act at low pH
Where does the pool of available amino acids come from?
Diet, digestion, De novo synthesis (DDD)
What are the three ways the amino acid pool is used?
- Ketogenesis
- Gluconeogenesis
- Synthesis of N-containing nonproteins
What amino acids are glucogenic?
Those that can be transformed and incorporated into the OAA (CAC, pyruvate)
What amino acids are ketogenic?
Those that can be transformed into acetyl CoA
What organisms fix nitrogen?
Cyanobacteria, rhizobia
Why is hyperammonemia damaging to the CNS?
Glutamine synthetase combines ammonium and glutamate to form glutamine, which changes the osmotic gradient in the brain.
Transaminases are a form of ________ reaction.
Double displacement reaction
Glucose-Alanine Cycle
Muscles: Glucose –> Pyruvate –> Ala (ALT)
Luver: Ala –> Pyruvate –> Glucose
What ratio is used to determine progression of liver disease?
AST/ALT
What do aquatic animals excrete?
Ammonia
What do amphibians excrete?
Urea
What do reptiles and insects excrete?
Uric Acid
Where does the urea cycle take place?
Mitochondria and cytosol of liver
Which inborn disorder of metabolism is associated with Marfanoid symptoms?
Homocystinuria
Where do the carbon skeletons used in AA synthesis come from?
- CAC (OAA)
- Glycolysis (pyruvate)
- PPP (R5P)
Where does the nitrogen used in AA synthesis come from?
Glu or Gln
Patchwork Assembly Model
Ancestral enzymes could bind a number of substrates to carry out the same reaction. Duplication, then divergence has led to the affinity and specificity we see today.
What does CBS do?
Catalyzes the formation of cystathionine
What does CGS do?
- Removes ammonia
- Cleaves cystathionine to yield Cys
What are tannins, alkaloids, natural flavorings, and salicylate derived from?
Phe & Tyr
Concerted Inhibition
Additive effect associated with 2+ inhibitors acting on an enzyme (usually the enzyme’s products)
What are key characteristics of the regulation of AA biosynthesis at the cellular level?
- Several isozymes regulate the same reaction
- Overlapping feedback inhibition (e.g. Leu and Ile)
- Negative feedback
