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MSAP 2015 > BIOCHEMISTRY: RENAL SYSTEM > Flashcards

BIOCHEMISTRY: RENAL SYSTEM Flashcards

1
Q

How does Ka and pKa relate with acid strenght?

A

the higher the Ka the stronger the acid (lower pH)

the lower the pKa the stronger the acid (lower pH)

pKa = -logKa

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2
Q

In animals there are only 3 enzyme catalyzed reactions that may fix free NH4+ into organic molecules. What are they?

A
  1. Glutamate dehydrogenase
  • If glutamate is formed, it’s called reductive amination
  • Glutamate + NAD+ ⇔ NH3 + NADH + a-Ketoglutarate
  1. Glutamine synthetase
  • Glutamate + ATP + NH4+ ⇒ Glutamine +ADP + Pi
  • Scavenger of ammonia in peripheral tissue

3.Carbamoyl phosphate synthetase 1

  • 1st reaction in Urea cycle
  • HCO3- + NH4+ ⇒ Carbamoyl-P
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3
Q

Under what conditions may humans release ammonia in the urine?

A

An attempt to relase metabolic acidosis

Acid base affect

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4
Q

During a fasting state, what is the process that leads to the urea cycle?

A
  • Body protein is degraded
  • Amino acids flood into the blood
  • Amino acids go the liver
  • NH3 groups are removed

–Forms keto acids

–Keto acids carbon skeletons are converted into glucose or ketone bodies (to help support energy needs for body)

•NH3 must be detoxified

–Urea cycle

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5
Q

What is the objective of most transaminase (TA) reactions in the liver?

A
  • Collect N in GLU for eventual disposal in urea cycle
  • If the N is in the form of Glu then one (1) NH3 may be released

–Via the Glutamate dehydrogenase reaction

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6
Q

When the body delivers excess nitrogen to the liver via glutamine, what happens?

A
  • Glutamine contains two nitrogen groups
  • Therefore, Gln may release two (2) NH3 for detoxification in the urea cycle

–First via the Glutaminase reaction

–Second via the Glutamate dehydrogenase reaction

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7
Q

What is the process of delivering ammonia to the liver from tissues?

A
  • NH3 collected in GLN Delivered to the liver
  • Formation of GLU in liver
  1. –First-Glutaminase
  2. –(GLN → GLU + NH3)
  3. –Then-Glutamate dehydrogenase
  4. –(GLT → α-KG + NH3)
  5. –oxidative deamination in liver
  6. –Regeneration of αKG
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8
Q

Which of the following reactions is considered to be irreversible?

A.Transamination reaction

B.Glutamate dehydrogenase

C.Glutaminase

A

C. Glutaminase

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9
Q

What is the first step in the urea cycle?

A

NH4+ + HCO3- ⇒ Carbamoylphosphate (by way of CPS1)

  • Mitochondrial reaction
  • CPS1 is the rate limiting (and regulated) step of urea cycle.
  • CPSI is one of 3 mammalian enzymes that can “fix” ammonia into an organic cmpd
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10
Q

Show how fumarate may be converted back to OAA and aspartate

A

•Recall the TCA cycle:

  1. Fumarate may be converted to malate
  2. Malate may be oxidized to oxaloacetate (OAA)

•OAA may be transaminated to aspartate (glutamate donor)

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11
Q

In the liver, AST is an exception to the rule. What is it?

A

Typically the objective of TA in the liver is to collect N in GLU for eventual disposal in urea cycle (via Glutamate dehydrogenase)

In the liver, the general rule for aminotransferase reactions is the net formation of GLU

In the liver, the net flux of the AST reaction is towards the formation of aspartate.

This means that ASP is always at a high concentration for delivery of the second N into urea cycle.

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12
Q

What is the final step inthe urea cycle?

A

Conversion of Arginine to Urea (via Arginase)

  • Arginase is the final step in the urea cycle
  • Found only in the liver (cytoplasm)
  • Releases one molecule of urea, and reforms ornithine
  • ornithine transported to mitochondria
  • Urea diffuses to the blood, excreted in the urine
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13
Q

How does the 1st & 2nd nitrogen enter into the urea cycle?

A

1st enters in as free ammonia (happens in the mitochondria)

2nd enters in as aspartate (happens in cytoplasm)

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14
Q

What is the feed foward mechanism to regulate the urea cycle dependent upon?

A

Allosteric regulation of CPS1 by N-Acetylglutamate

Formation of N-Acetylglutamate is dependent on:

  1. Glutamate
  2. Arginine

Positive feed-forward regulation on the urea cycle

  1. Regulation of CPS1 by N-acetylglutamate

–Synthesis of N-acetylglutamate dependent on [GLU]

–Synthesis of N-acetylglutamate is stimulated by ARG

–Note that ARG is produced by urea cycle

  1. Regulation by substrate []

–The rate of NH4+ production

  1. Induction (synthesis) of the cycle enzymes with increase in protein metabolism (genetic regulation)

–Fasting & high-protein diet

–Increased gene expression of urea cycle enzymes

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15
Q

Why is ammonia toxic to humans?

A

• α-ketoglutarate is converted to glutamate

–Via glutamate dehydrogenase enzyme

• Reductive amination direction

–Results in decreased TCA cycle activity

–Reduced ATP synthesis

  • Don’t forget, your brain needs ATP
  • Glutamate is converted to glutamine

–Glutamine synthetase

–Results in high circulating glutamine levels

• Reduced GABA and glutamate levels, and increased levels of glutamine in the brain

–GABA is major inhibitory NT

–GLU is major excitatory NT

–GLN is an excitatory NT

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16
Q

What electrolytes are actively cotransported in the ascending loop of Henle?

A

In the ascending loop of Henle, Na, Cl, and K are actively reabsorbed (contributing to the interstitial osmotic gradient) by the Na/K/Cl (NKCC) cotransporter.

In addition, Mg, K, and Ca are passively reabsorbed as they diffuse through paracellular routes.

The thick ascending limb is impermeable to water, resulting in dilution of the tubular fluid.

The NKCC channels of the thick ascending limb are the targets for loop diuretics(Furosemide, Bumetanide, Ethacrynic Acid). By blocking reabsorption of ions in the thick ascending limb, reabsorption of water in the thin descending limb is halted.

17
Q

In the final step of the urea cycle, arginine is hydrolyzed to yield urea and which non-proteinogenic amino acid?

A

Arginase I catalyzes hydrolysis of arginine to yield urea and regenerate ornithine

18
Q

Describe the rate limiting reaction of the urea cycle.

A

The first step, the conversion of CO2 and ammonia to carbamoyl phosphate, is rate-limiting

Enzyme: carbamoyl phosphate synthetase I

Obligate activator: N-acetyl-glutamate

This step consumes 2 ATP

This step takes place in the mitochondria

The ammonia in this reaction provides the 1st amine groups in urea

Note: HCO3- + NH4+ is equivalent to CO2 + NH3 + H2O

MSAP 2015 (10 decks)

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