L13 - Metabolic processes of the renal cortex and medulla

Question 1

Renal fuel metabolism varies with:

Answer 1

• Normal fed state
• Metabolic acidosis
• Fasting

Question 2

N-compounds in urine (with daily amt)

Answer 2

(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)

Question 3

Glutaminase

Answer 3

Renal enzyme that catalyzes:

Glutamine + H₂O –> Glutamate + NH₄⁺

Question 4

Glutamine synthetase

Answer 4

Renal enzyme that catalyse:

Glutamate + NH₄⁺ –> Glutamine

(ATP converted to ADP + Pi at this process)

Question 5

Synthesis & Degradation of Glutamine

Answer 5

Question 6

Glutamate dehydrogenase

Answer 6

Renal enzyme that catalyses:

Glutamate –> α-ketoglutarate + NH₄⁺

Question 7

Renal source of NH₄⁺ production from glutamine

Answer 7

The series of deamination of glutamine:

Glutamine to glutamate (glutaminase)

Glutamate to α-ketoglutarate (glutamate dehydrogenase)

Question 8

Factor affecting Renal uptake of glutamine

Answer 8

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

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

Question 9

Carbonic anhydrase

Answer 9

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)

Question 10

Renal glutamine metabolism overview

Answer 10

Question 11

Major fuel sources for the kidney

Answer 11

Lactate (normal state)

Glutamine (acidosis)

Fatty acids (fasting state)

Glucose

Question 12

Renal fuel source in fed state

Answer 12

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

Glucose (25%)

Glutamate (15%)

Fatty Acid (15%)

Question 13

Renal fuel source in fasting

Answer 13

Fatty acid (60%)

Glutamate (25%)

Lactate (15%)

Glucose (0%)

Question 14

Renal fuel source in acidosis

Answer 14

Glutamate (40%)

Fatty acid, glucose, lactate (@ 20%)

Question 15

Glutamine as renal fuel molecules

Answer 15

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

Question 16

Source of glucose utilised in renal medulla

Answer 16

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

Question 17

Nephric blood supply overview

Answer 17

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

Question 18

Glutamine metabolism in the kidney

Answer 18

Mitochondria:

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

Cytoplasm:

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

Question 19

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

Answer 19

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)

Question 20

amino acid metabolism errors and urine

Answer 20

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

Question 21

Phenylalaine metabolism errors overview

Answer 21

Question 22

Pheylalaine Degradation

Answer 22

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

Question 23

Tyrosine metabolism errors overview

Answer 23

Question 24

Tyrosine degradation

Answer 24

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

Question 25

Phenylketonuria (classical)

Answer 25

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

Question 26

Phenylketonuria (non-classical)

Answer 26

**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

Question 27

Alcaptonuria

Answer 27

Autosomal recessive disorder to phenylalaine and tyrosine metabolic pathway **Defective enzyme:** Homogentisate oxidase Homogentisate/homogentisic acid will accumulate, leading to **black urine and arthritis**

Question 28

Tyrosinemia I

Answer 28

Disorder to phenylalaine and tyrosine metabolic pathway Missing enzyme: Fumarylacetoacetate hydrolase Accumulation: Fumarylacetoacetate Symptoms: Liver failure, early death

Question 29

Tyrosinemia II

Answer 29

Disorder to phenylalaine and tyrosine metabolic pathway Missing enzyme: tyrosine aminotransferase Accumulation: Tyrosine Symptoms: Neurological damage, mental retardation

Question 30

Methionine metabolic error overview

Answer 30

Question 31

Cystathioninuria

Answer 31

Disorder to methionine metabolic pathway missing enzyme: cystathionase (convert cystathionine to cysteine) Accumulation: Cystathionine Benign cardiovascular complications and neurological problems

Question 32

Homocysteinemia

Answer 32

Disorder to methionine metabolic pathway missing enzyme: Methionine synthase or FH4 reductase or cysthathionine synthase Accumulation: Cystathionine Benign cardiovascular complications and neurological problems

Question 33

Alternative fate when homocysteine builds up

Answer 33

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

Question 34

Branched chain amino acids

Answer 34

aka BCAA; leucine, isoleucine, valine

Question 35

BCAA metabolism

Answer 35

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

Question 36

Maple syrup Urine Disease (MSUD)

Answer 36

Disorder of BCAA metabolism Defective BCKD (branched chain α-keto acid dehydrogenase) protein complex accumulation of α-keto acid of BCAA Mental retardation

Question 37

Sepsis/trauma and glutamine

Answer 37

In sepsis and trauma, glutamine is released from skeletal muscle Uptake by tissues - immune response tissue repair

Question 38

overnight fast and glutamine

Answer 38

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

Question 39

Amino acid release from skeletal muscle

Answer 39

Glutamine and alanine (derived from BCAA)

Question 40

glutamine formation from amino groups of BCAA

Answer 40

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.

Question 41

BCAA to glutamine and alanine

Answer 41