L36 – Metabolic Processes of the Renal Cortex and Medulla Flashcards

(44 cards)

1
Q

Glucose utilized in the renal medulla is produced where?

A

in the renal cortex

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2
Q

How does fuel dependence in the normal fed, metabolic acidosis and fasting states change?

A

Normal fed state - mainly lactate, then glucose

Metabolic acidosis- mainly Glutamine

Fasting- mainly Fatty acids

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3
Q

What are the 4 main N-compounds in urine?

A

Urea
NH4+
Creatinine
Uric acid

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4
Q

Which of the N-compounds can cause gout? Why?

A

Uric acid

Lowest solubility, could be trapped in joints and crystallize > gout

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5
Q

Reason for more supply to renal cortex than to medulla?

A

Medulla is less vascularized due to the need to maintain counter-current multiplier system > less vessels

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6
Q

Medulla receives less blood. Consequence on cell metabolism of medulla?

A

Medulla rely on anaerobic respiration, cannot rely on oxidative phosphrylation due to lack of O2

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7
Q

How is NH4+ extracted and secreted in urine? (Start with arterial glutamine)

A

Arterial glutamine > Glutmaine in kidney cells (in mitochondria and cytosol)

Glutamine > Glutamate + NH4+

Deamination via Glutaminase enzyme

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8
Q

What enzymes are involved in conversion between Glutamine and Glutamate?

A
Glutamine > Glutamate 
use Glutaminase (release NH4+)

Glutamate > Glutamine
use ATP & Glutamine synthetase

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9
Q

What is produced in ammoniagenesis in kidney via glutamine?

A

Glutamine > HCO3- + NH3

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10
Q

Chemical pathway from glutamine to a-Ketoglutarate?

A

Glutamine > (glutaminase) > Glutamate + NH3 > (glutamate dehydrogenase GDH) > a-Ketoglutarate

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11
Q

How is glutamine converted in kidneys for gluconeogenesis?

A

Glutamine > glutamate > A-Ketoglutarate > TCA cycle

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12
Q

Where in kidney is lactate for conversion to pyruvate?

A

Kidney cortex

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13
Q

How is lactate in cortex of kidney converted to glucose for use in medulla?

A

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

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14
Q

How does fasting state change the renal metabolism ?

A

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

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15
Q

Why is NH3 produced in conversion of glutmaine to a-Ketoglutarate released into filtrate ?

A

for acid-base balance

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16
Q

What happens to the lactate produced by medulla after anaerobic respiration?

A

Transported back to cortex to undergo conversion to form glucose again

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17
Q

How is OAA shuttled out of the mitochondria to form PEP?

A

There are no OAA transporters at mitochondria

Shuttled out in:

1) Aspartate (via transamination)
2) Malate (via reduction)

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18
Q

What occurs if there is an excess of Acetyl CoA to OAA in mitochondria of renal cell?

A

Acetyl- CoA converted to ketone bodies

19
Q

In fasted state, how does fatty acid oxidation prevent using up PEP to form Acetyl CoA

A

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

20
Q

What happens to the 2 molecules formed by OAA after being transported out of mitochondria?

A

OAA inside mitochondria > Aspartate + Malate > reconvert to OAA in cytosol

21
Q

What is the energy source for turning OAA to PEP?

22
Q

Is the medulla of kidney reliant on blood circulation for supply of energy?

A

No, depends on cortical cells to produce glucose for anaerobic respiration

23
Q

What does the Renal uptake of glutamine depend on?

A

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

24
Q

What are the 4 functions of glutamine in kidneys?

A

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

25
Apart from lactate, what other substance can kidney use to produce PEP via the TCA cycle to undergo gluconeogenesis?
Glutamine > a-Ketoglutarate
26
Inborn errors of amino acid metabolism can be observed by?
Urine composition
27
Name one Disorder in Branched Chain Amino Acid (BCAA) Metabolism
Maple syrup urine disease
28
What is the cause of Maple syrup urine disease?
missing or defective branched chain α-ketoacid dehydrogenase
29
What is the normal role of branched chain α-ketoacid dehydrogenase (BCKD complex)?
Responsible for dehydrogenation and decarboxylation of Branched Chain amino acids
30
What are the Branched chain amino acids?
Valine, Leucine, Isoleucine
31
What process preceeds the use of BCKD complex in Branched Chain Amino Acid metabolism?
Amino acid > TRANSAMINATION > OXIDATIVE DECARBOXYLATION by BCKD complex
32
What gives the distinct sweet odour in Maple Syrup Urine Disease?
Accumulation of BCAA α-ketoacids
33
What is accumulated in Phenylketouria PKU disease?
accumulation of the | amino acid phenylalanine
34
What is defective to cause PKU?
1) defects in phenylalanine hydroxylase (PAH) 2) defects in dihydropteridine reductase 3) defective biosynthesis of tetrahydrobiopterin (BH4) from BH2 (BH4 used in Phenylalanine to Tyrosine conversion)
35
If phenylalanine hydroxylase is defective, what conversion is blocked?
Phenylalanine > Tyrosine conversion is blocked
36
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
37
PKU patient urine has distinct smell? What molecule causes this smell?
"Musty odour" lack of phenylalanine hydroxylase > phnylalanine accumulate and forms phenylacetate and phenyllactate phenyacetate accumulate and give smell
38
What group is removed from methionine to form homocysteine?
Methyl group
39
How can Homocysteine be reconverted into methionine?
By using methyl group from FH4
40
How can Homocysteine be converted to cysteine?
via a reverse trans-sulphurylation pathway
41
What is defective in methionine metabolism pathway to cause homocysteinaemia?
Defects in: 1) Methionine synthase 2) Tetrahydrofolate reductase 3) Cystathionince synthase 4) B6 or B12 deficiency
42
What are the symptoms of Homocysteinaemia ?
1) High risk of atherosclerosis | 2) Neurological problem
43
What occurs to accumulated homocysteine?
Form dimers homocystine and excreted in urine
44
How does Tyrosinemia II arise?
Defective or missing Tyrosine aminotransferase, cause Tyrosine accumulation > neural defect