L36 – Metabolic Processes of the Renal Cortex and Medulla Flashcards
(44 cards)
Glucose utilized in the renal medulla is produced where?
in the renal cortex
How does fuel dependence in the normal fed, metabolic acidosis and fasting states change?
Normal fed state - mainly lactate, then glucose
Metabolic acidosis- mainly Glutamine
Fasting- mainly Fatty acids
What are the 4 main N-compounds in urine?
Urea
NH4+
Creatinine
Uric acid
Which of the N-compounds can cause gout? Why?
Uric acid
Lowest solubility, could be trapped in joints and crystallize > gout
Reason for more supply to renal cortex than to medulla?
Medulla is less vascularized due to the need to maintain counter-current multiplier system > less vessels
Medulla receives less blood. Consequence on cell metabolism of medulla?
Medulla rely on anaerobic respiration, cannot rely on oxidative phosphrylation due to lack of O2
How is NH4+ extracted and secreted in urine? (Start with arterial glutamine)
Arterial glutamine > Glutmaine in kidney cells (in mitochondria and cytosol)
Glutamine > Glutamate + NH4+
Deamination via Glutaminase enzyme
What enzymes are involved in conversion between Glutamine and Glutamate?
Glutamine > Glutamate use Glutaminase (release NH4+)
Glutamate > Glutamine
use ATP & Glutamine synthetase
What is produced in ammoniagenesis in kidney via glutamine?
Glutamine > HCO3- + NH3
Chemical pathway from glutamine to a-Ketoglutarate?
Glutamine > (glutaminase) > Glutamate + NH3 > (glutamate dehydrogenase GDH) > a-Ketoglutarate
How is glutamine converted in kidneys for gluconeogenesis?
Glutamine > glutamate > A-Ketoglutarate > TCA cycle
Where in kidney is lactate for conversion to pyruvate?
Kidney cortex
How is lactate in cortex of kidney converted to glucose for use in medulla?
1) Lactate in cortex converted to pyruvate
2) Pyruvate converted to Acetyl- CoA
3) Acetyl-CoA used in TCA cycle inside mitochondria
4) OAA forms PEP via enzyme PEPCK
5) PEP forms glucose by gluconeogenesis
6) Glucose used in anaerobic respiration in medulla
How does fasting state change the renal metabolism ?
Fasting = use mainly Fatty acids
Fatty acid converted to Acetyl CoA by B- oxidation pathway
Acetyl-CoA used in TCA cycle … form PEP
PEP converted to glucose for use in medulla
Why is NH3 produced in conversion of glutmaine to a-Ketoglutarate released into filtrate ?
for acid-base balance
What happens to the lactate produced by medulla after anaerobic respiration?
Transported back to cortex to undergo conversion to form glucose again
How is OAA shuttled out of the mitochondria to form PEP?
There are no OAA transporters at mitochondria
Shuttled out in:
1) Aspartate (via transamination)
2) Malate (via reduction)
What occurs if there is an excess of Acetyl CoA to OAA in mitochondria of renal cell?
Acetyl- CoA converted to ketone bodies
In fasted state, how does fatty acid oxidation prevent using up PEP to form Acetyl CoA
FA- oxidation > form Acetyl CoA + NADH
no need for PEP to form more Acetyl CoA, PEP > gluconeogenesis > glucose
NADH inhibits pyruvate dehydrogenase to inhibit conversion of PEP > Pyruvate > Acetyl CoA
What happens to the 2 molecules formed by OAA after being transported out of mitochondria?
OAA inside mitochondria > Aspartate + Malate > reconvert to OAA in cytosol
What is the energy source for turning OAA to PEP?
GTP
Is the medulla of kidney reliant on blood circulation for supply of energy?
No, depends on cortical cells to produce glucose for anaerobic respiration
What does the Renal uptake of glutamine depend on?
The need to excrete H+ to maintain blood pH
More H+ need to be excreted, more glutamine uptake to produce NH3 for acid-base balance in urine
What are the 4 functions of glutamine in kidneys?
1) For acid- base balance, Glutmaine conversion to NH3 and HCO3- can buffer H+
2) Act as source of new carbon atoms in gluconeogenesis
3)Remove excess nitrogen in body by ammoniagenesis
Used as fuel > conversion to a-Ketogluturate used in TCA