L13 - Metabolic processes of the renal cortex and medulla Flashcards

1
Q

Renal fuel metabolism varies with:

A
  • Normal fed state
  • Metabolic acidosis
  • Fasting
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2
Q

N-compounds in urine (with daily amt)

A

(unit is g/day)

1) Urea (12-24)
2) Creatinine (1.0-1.8)
3) Uric Acid (0.2-0.8)
4) NH4+ (0.2-1.0; as high as 10 in acidosis)

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3
Q

Glutaminase

A

Renal enzyme that catalyzes:

Glutamine + H2O –> Glutamate + NH4+

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4
Q

Glutamine synthetase

A

Renal enzyme that catalyse:

Glutamate + NH4+ –> Glutamine

(ATP converted to ADP + Pi at this process)

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5
Q

Synthesis & Degradation of Glutamine

A
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6
Q

Glutamate dehydrogenase

A

Renal enzyme that catalyses:

Glutamate –> α-ketoglutarate + NH4+

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7
Q

Renal source of NH4+ production from glutamine

A

The series of deamination of glutamine:

Glutamine to glutamate (glutaminase)

Glutamate to α-ketoglutarate (glutamate dehydrogenase)

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8
Q

Factor affecting Renal uptake of glutamine

A

Depends on the need to excrete H+ to maintain blood pH.

[note: glutamine is small enough to enter glomerular filtrate]

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9
Q

Carbonic anhydrase

A

Renal enzyme, catalyze conversion of H2O and CO2 to H+ and HCO3-

H+ excreted via urine

HCO3- secreted back to blood

(control of blood pH)

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10
Q

Renal glutamine metabolism overview

A
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11
Q

Major fuel sources for the kidney

A

Lactate (normal state)

Glutamine (acidosis)

Fatty acids (fasting state)

Glucose

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12
Q

Renal fuel source in fed state

A

Lactate (45%; transported to blood-rich cortical cells for gluconeogenesis)

Glucose (25%)

Glutamate (15%)

Fatty Acid (15%)

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13
Q

Renal fuel source in fasting

A

Fatty acid (60%)

Glutamate (25%)

Lactate (15%)

Glucose (0%)

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14
Q

Renal fuel source in acidosis

A

Glutamate (40%)

Fatty acid, glucose, lactate (@ 20%)

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15
Q

Glutamine as renal fuel molecules

A

Glutamine is used as fuel in the normal fed state, and
to a greater extent during fasting and metabolic acidosis.

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16
Q

Source of glucose utilised in renal medulla

A

Glucose utilised in the renal medulla is produced in the renal cortex

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17
Q

Nephric blood supply overview

A

Blood supply to cortical (short-looped) nephrons is greater than that to the juxtamedullary/medullary (long-looped) nephrons

18
Q

Glutamine metabolism in the kidney

A

Mitochondria:

glutamine -> glutamate -> α-ketogutarate -> [enters TCA cycle] -> Oxaloacetic acid (OAA) ->

Cytoplasm:

-> OAA -> PEP -> converted to glucose via gluconeogenesis, or pyruvate

19
Q

Translocation of electrons (in form of OAA) from mitochondria to cytoplasm

A

Malate-aspartate shuttle:

  • OAA converted to aspartate, aspartate move out of mitochondria, aspartate reconvert to OAA
  • OAA converted to malate (with NADH to NAD+), malate move out of mitochondria, malate convert to OAA (NAD+ to NADH)
20
Q

amino acid metabolism errors and urine

A

Materials excreted in urine can reflect on accumulated amino acid metabolites; therefore Inborn errors of amino acid metabolism will be manifestations in the urine

21
Q

Phenylalaine metabolism errors overview

A
22
Q

Pheylalaine Degradation

A

1) Main pathway:

Phenylalaine [phenylalaine hydroxylase> Tyrosine [tyrosine aminotransferase> Homogentisate [homogenisate oxidase> Fumarylacetoacetate [fumarylacetoactate hydrolase> fumarate and acetoacetate

2) Alternate pathway

Phenylalaine [transamination> Phenylpyruvate -> Phenylacetate (musty odour) and Phenyllactate

23
Q

Tyrosine metabolism errors overview

A
24
Q

Tyrosine degradation

A

Tyrosine [tyrosine aminotransferase> Homogentisate [homogenisate oxidase> Fumarylacetoacetate [fumarylacetoactate hydrolase> fumarate and acetoacetate

25
Q

Phenylketonuria (classical)

A

Autosomal recessive

defective enzyme: phenylalaine hydroxylase (hepatic)

Phenylalaine cannot be converted to tyrosine; accumulation of phenylalaine which is converted to phenylpyruvate, which can be found in urine. Leads to brain and nerve damage, mental retardation

26
Q

Phenylketonuria (non-classical)

A

defective enzyme: Dihidropteridine

Phenylalaine cannot be converted to tyrosine; accumulation of phenylalaine which is converted to phenylpyruvate, which can be found in urine. Leads to brain and nerve damage, mental retardation

Dihydropteridine

Convert quinoloid dihydrobiopterin (BH2) to tetrahydrobiopterin (BH4). BH4 participate in the conversion of phenylalaine to tyrosine via phenylalaine hydroxylase, where it is converted to BH2. Therefore with defective dihydropteridine, BH4 cannot be regenerated from BH2, and phenylalaine-tyrosine conversion stops

27
Q

Alcaptonuria

A

Autosomal recessive disorder to phenylalaine and tyrosine metabolic pathway

Defective enzyme: Homogentisate oxidase

Homogentisate/homogentisic acid will accumulate, leading to black urine and arthritis

28
Q

Tyrosinemia I

A

Disorder to phenylalaine and tyrosine metabolic pathway

Missing enzyme: Fumarylacetoacetate hydrolase

Accumulation: Fumarylacetoacetate

Symptoms: Liver failure, early death

29
Q

Tyrosinemia II

A

Disorder to phenylalaine and tyrosine metabolic pathway

Missing enzyme: tyrosine aminotransferase

Accumulation: Tyrosine

Symptoms: Neurological damage, mental retardation

30
Q

Methionine metabolic error overview

A
31
Q

Cystathioninuria

A

Disorder to methionine metabolic pathway

missing enzyme: cystathionase (convert cystathionine to cysteine)

Accumulation: Cystathionine

Benign cardiovascular complications and neurological problems

32
Q

Homocysteinemia

A

Disorder to methionine metabolic pathway

missing enzyme: Methionine synthase or FH4 reductase or cysthathionine synthase

Accumulation: Cystathionine

Benign cardiovascular complications and neurological problems

33
Q

Alternative fate when homocysteine builds up

A

Disulphide linkage of homocysteine, forming homocystine which will be excreted in urine

34
Q

Branched chain amino acids

A

aka BCAA; leucine, isoleucine, valine

35
Q

BCAA metabolism

A

BCAA (Leucine, isoleucine, valine) converted by branched chain α-keto acid dehydrogenase (BCKD) protein complex

36
Q

Maple syrup Urine Disease (MSUD)

A

Disorder of BCAA metabolism

Defective BCKD (branched chain α-keto acid dehydrogenase) protein complex

accumulation of α-keto acid of BCAA

Mental retardation

37
Q

Sepsis/trauma and glutamine

A

In sepsis and trauma, glutamine is released from skeletal muscle

Uptake by tissues - immune response tissue repair

38
Q

overnight fast and glutamine

A

BCAA in skeletal muscles converted to glutamine and released in case of overnight fast

39
Q

Amino acid release from skeletal muscle

A

Glutamine and alanine (derived from BCAA)

40
Q

glutamine formation from amino groups of BCAA

A

BCAA converted to α ketoacid, which is converted to glutamate via transamination. Via enzyme glutamine synthase, glutamate is converted into glutamine with NH3 derived from glutamate through purine nucleotide cycle.

41
Q

BCAA to glutamine and alanine

A