L36 – Metabolic Processes of the Renal Cortex and Medulla Flashcards Preview

MBBS I CPRS > L36 – Metabolic Processes of the Renal Cortex and Medulla > Flashcards

Flashcards in L36 – Metabolic Processes of the Renal Cortex and Medulla Deck (44):
1

Glucose utilized in the renal medulla is produced where?

in the renal cortex

2

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

3

What are the 4 main N-compounds in urine?

Urea
NH4+
Creatinine
Uric acid

4

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

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

5

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

6

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

7

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

8

What enzymes are involved in conversion between Glutamine and Glutamate?

Glutamine > Glutamate
use Glutaminase (release NH4+)

Glutamate > Glutamine
use ATP & Glutamine synthetase

9

What is produced in ammoniagenesis in kidney via glutamine?

Glutamine > HCO3- + NH3

10

Chemical pathway from glutamine to a-Ketoglutarate?

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

11

How is glutamine converted in kidneys for gluconeogenesis?

Glutamine > glutamate > A-Ketoglutarate > TCA cycle

12

Where in kidney is lactate for conversion to pyruvate?

Kidney cortex

13

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

14

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

15

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

for acid-base balance

16

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

Transported back to cortex to undergo conversion to form glucose again

17

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)

18

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

Acetyl- CoA converted to ketone bodies

19

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

20

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

21

What is the energy source for turning OAA to PEP?

GTP

22

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

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

23

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

24

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

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

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