Crystal Arthropathies Flashcards
which base is N-containing single ring structure
pyrimindine
which base is N-containing double ring structure
purine
which nucleotides are purines
A and G
which nucleotides are pyrimidines
C, T, and U
difference in DNA and RNA for nucleotides
DNA has T and RNA has U
what are the two pathways to synthesize purines?
de novo synthesis pathway and salvage pathway
explain the de novo pathway to synthesize purines
Glutamine is used to transfer an N to PRPP, then a base is built on the N, the nucleotide product is inosine monophosphate (IMP)
what is used in the de novo synthesis pathway?
glutamine
what is the nucleotide product of the de novo synthesis pathway
inosine monophosphate (IMP)
IMP can then be used to make what?
AMP or GMP
ATP to make GMP
GTP to make AMP
why is reciprocal control in the de novo synthesis useful?
Helps ensure you are not making all of one type of purine and not enough of the other
what purine base is made from the de novo synthesis pathway?
hypoxanthine
what does the salvage pathway use?
Uses hypoxanthine, guanine, and adenine bases that already exist
what are the two enzymes used in the salvage pathway?
- hypoxanthine-guanine phosphoribosyl transferase
- adenine phosphoribosyltransferase
what does hypoxanthine-guanine phosphoribosyl transferase do?
catalyzes the addition of phosphoribose (sugar +P) from PRPP to:
- Hypoxanthine to make IMP
- guanine to make GMP
what does adenine phosphoribosyltransferase do?
catalyzes the addition of phosphoribose (sugar + P) from PRPP to:
adenine to make AMP
what is the pathway for pyrimidine nucleotide synthesis
de novo pathway
how is the de novo pathway different in pyrimidine than purine synthesis
in purimidine, it involves making an intermediate pyrimidine ring first, then attaching a ribose-5-P (via PRPP)
what are the substrates for the pyrimidine ring in pyrimidine synthesis
- carbamoyl phosphate (made from glutamine, ATP, CO2)
- aspartate
during the de novo pathway for pyrimidine, what is the nucleotide intermediate when the pyrimidine ring is attached to PRPP?
UMP
how is CTP made from UMP
UMP is phosphorylated via kinases to make UTP, UTP is aminated to make CTP (glutamine provides the N)
how to make dTMP from UMP
UMP is phosphorylated (kinase) to make UDP, then converted to dUMP, dUMP is methylated to dTMP using folate coenzyme
what removes P’s from nucleotides to relase nucleosides
nucleotidases
what happens when pyrimidine bases are degraded
cytosine to uracil and ultimately alanine
what happens when purine bases are degraded
first to xanthine, then uric acid, and then excreted in urine
what is the enzyme that converts hypoxanthine to xanthine, and xanthine to uric acid?
xanthine oxidase
what leads to gout?
hyperuricemia
what is hyperuricemia
underexcretion (most common) or overproduction (less common) of uric acid
what is chronic tophaceous gout
Nodular masses of monosodium urate crystals (tophi) may be deposited in soft tissues
what is the enzyme that is responsible for the degradation of uric acid?
uricase
what is gout?
joint inflammation due to deposition of urate crystals
what results in acute gouty arthritis?
monosodium urate crystal precipitation
in a patient with acute gout, how does the joint become inflamed
Urate crystals are phagocytosed by macrophages, activating them, they then release chemokines that attract neutrophils into the joint, found within the synovial fluid, Neutrophils mediate joint inflammation
people with acute gout tends to have pain in which joints
1st metatarsal-phalangeal joint, insteps, ankles, heels, knees, wrists, elbows, finger, Lower limbs are more often affected than upper
Chronic gout leads to ?
chronic arthritis with joint erosion, chronic inflammation, development of pannus, and development of tophi
what is the pathognomonic hallmark of gout
tophi
what are tophi
uric acid crystals that accumulate in and around the affected joint
how does Lesch-Nyhan Syndrome happen?
deficiency of HGPRT
Lesch-Nyhan Syndrome can lead to?
hyperuricemia because increase in uric acid
what is calcium pyrophosphate crystal deposition disease (CPPD) also known as ?
pseudogout
most cases of pseudo gout are?
sporadic
what causes pseudogout?
caused by the buildup of calcium pyrophosphate crystals in the joints, macrophages phagocytose the crystals, recruiting neutrophils and causing inflammation
what is used to distinguish what type of arthritis a person has?
synovial fluid analysis
what are the 3 C’s when doing the synovial fluid analysis
Crystals
Cells
Culture
when the cells (seen in synovial fluid analysis) are super high, it’s usually what
septic arthritis
what are some anti-gout agents
- target the inflammation (corticosteriods and colchicine)
- analgesics (NSAIDs)
- decrease uric acid production
- increase uric acid excretion
how does colchine effect inflammation
Blocks the migration of leukocytes (most importantly neutrophils), thereby decreasing the inflammatory response
what is the most serious adverse effect of colchine
bone marrow depression
