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Printable Handouts
Navigable Slide Index
- Introduction
- Talk outline
- Yin and Yang of urate
- What is urate?
- Overall picture of urate metabolism
- ~90% of gout patients have low urate excretion
- ~90% of filtered urate is reabsorbed in the kidney
- Urate has to cross epithelial cell layer
- Urate cannot permeate into the cell membrane
- Urate can pass through paracellular channel
- Transporters in the kidney: main routes of urate
- Transporters and modulators
- Transepithelial transport
- Placenta urate transport via paracellular route
- Paracellular route of urate
- Urate may be reabsorbed by solvent drag
- Urate kidney reabsorption
- Obstacles for urate entry to proximal tubular cells
- Urate enters proximal tubular cells via URAT2
- URAT1 acts as a urate-anion exchanger
- In vivo evidence of URAT1 as a urate transporter
- How does urate exit proximal tubular cells?
- GLUT9 encoded by SLC2A9 transports urate
- SLC2A9-expressed oocytes urate kinetics
- SLC2A9 mediates urate exit is voltage dependent
- In vivo evidence of SLC2A9 as a urate transporter
- Two isoforms of SLC2A10
- SLC2A9-L expression in tubular cells
- URAT1 and SLC2A9 colocalization
- Current model of urate reabsorption
- SLC2A9 may be a rate-limiting urate transporter
- Uricosuric drugs target URAT1 and SLC2A10
- Some ARBs are uricosuric
- Kidney urate secretion
- Urate entery from blood to proximal tubular cells
- Urate is likely to be secreted by NPTs
- Loop and thiazide diuretics secretion
- Organic anions secretion by OAT1/3-NPTs
- Mutation in ABCG2 gene locus
- ABCG2 mediates intestinal urate excretion
- Urate metabolism and therapeutic targets
- Conclusions
- Acknowledgements
Topics Covered
- Urate physiology and pathophysiology
- Physiology of trans-epithelial movement of the solute
- Urate handling in the kidney
- Urate handling in the intestine
- Drugs and urate
Talk Citation
Sakurai, H. (2016, May 31). Transport mechanism of urate in humans [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved November 21, 2024, from https://doi.org/10.69645/JABM4067.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Hiroyuki Sakurai has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
A selection of talks on Gastroenterology & Nephrology
Transcript
Please wait while the transcript is being prepared...
0:00
Hello,
my name is Hiroyuki Saturai,
professor of pharacology, Kyorin
University School of Medicine,
Tokyo, Japan.
Today, I'd like to discuss
urate transport in our body.
I will try hard to explain
physiological principles
of urate transport so that my talk
is applicable not only to urate,
but also to many negatively
charged xenobiotics
or endogenous substrate.
0:29
So this is the agenda for this talk.
I will briefly discuss about
what urate is doing in our body.
Then we move to the physiology
of trans-epithelial movement
of the solute.
Then I will come back
to urate handling
and especially in the two key
organs in urate metabolism,
kidney and the intestine.
Then I will finish with drugs
that affect urate transport,
either a treatment or a side effect.
1:02
This is the yin and yang of
urate, so good and bad of urate.
If your uric acid is
very high, many doctors
think that you are in trouble
such as gout, or arthritis, kidney
stones.
However, urate itself
is a major antioxidant.
This is a bright side.
Some people say that once humans
could retain urate in their body,
vitamin C, also known as a
very strong anti-oxidant,
we lost an anti-oxidant possibly
at that time when we got urate.
But superoxide is generated
through urate production
by xanthine oxidase.
And this free radical, superoxide,
causes lots of trouble.
It appears that radical damage and
the anti-oxidant effect of urate
canceled out.
But other chemical dioxide
dark side still remains.
So here, the most problematic of
the urate is its poor solubility.
When urate becomes insoluble,
that forms crystal.
And then crystal is in the
kidney that causes kidney stones.
And then if the crystal
forms in your joint,
that activates innate immunity
then leads to inflammation.
And this is a gouty attack.