Flashcards in L36 – Metabolic Processes of the Renal Cortex and Medulla Deck (44):
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?
Which of the N-compounds can cause gout? Why?
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?
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?
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
Apart from lactate, what other substance can kidney use to produce PEP via the TCA cycle to undergo gluconeogenesis?
Glutamine > a-Ketoglutarate
Inborn errors of amino acid metabolism can be observed by?
Name one Disorder in Branched Chain Amino Acid (BCAA) Metabolism
Maple syrup urine disease
What is the cause of Maple syrup urine disease?
missing or defective branched chain α-ketoacid dehydrogenase
What is the normal role of branched chain α-ketoacid dehydrogenase (BCKD complex)?
Responsible for dehydrogenation and decarboxylation of Branched Chain amino acids
What are the Branched chain amino acids?
Valine, Leucine, Isoleucine
What process preceeds the use of BCKD complex in Branched Chain Amino Acid metabolism?
Amino acid > TRANSAMINATION > OXIDATIVE DECARBOXYLATION by BCKD complex
What gives the distinct sweet odour in Maple Syrup Urine Disease?
Accumulation of BCAA α-ketoacids
What is accumulated in Phenylketouria PKU disease?
accumulation of the
amino acid phenylalanine
What is defective to cause PKU?
1) defects in phenylalanine
2) defects in dihydropteridine reductase
3) defective biosynthesis of tetrahydrobiopterin (BH4) from BH2 (BH4 used in Phenylalanine to Tyrosine conversion)
If phenylalanine hydroxylase is defective, what conversion is blocked?
Phenylalanine > Tyrosine conversion is blocked
What accumulates if phenylalanine hydroxylase is blocked and what happens to accumulated molecule?
Phenylalanine cannot be converted to tyrosine
Accumulated phenylalanine forms phenylacetate or pheyllactate
PKU patient urine has distinct smell? What molecule causes this smell?
lack of phenylalanine hydroxylase > phnylalanine accumulate and forms phenylacetate and phenyllactate
phenyacetate accumulate and give smell
What group is removed from methionine to form homocysteine?
How can Homocysteine be reconverted into methionine?
By using methyl group from FH4
How can Homocysteine be converted to cysteine?
via a reverse trans-sulphurylation pathway
What is defective in methionine metabolism pathway to cause homocysteinaemia?
1) Methionine synthase
2) Tetrahydrofolate reductase
3) Cystathionince synthase
4) B6 or B12 deficiency
What are the symptoms of Homocysteinaemia ?
1) High risk of atherosclerosis
2) Neurological problem
What occurs to accumulated homocysteine?
Form dimers homocystine and excreted in urine