Nitrogen DLA part 2

Question 1

Summarize nitrogen metabolism

Answer 1

Nitrogen must be obtained from dietary sources:
– Proteins (amino acids)
• Needed for growth (protein synthesis) & amino acid derivatives
– Creatine, Purines, heme neurotransmitters, and pyrimidines, many others
There is no storage form of nitrogen in the mammal

Question 2

Describe the classifications of amino acids

Answer 2

Essential vs Non-essential Amino Acids

• Essential – cannot be synthesized by the body (human)
• Non-essential – can be synthesized by the body (human)

• Glucogenic vs Ketogenic Amino Acids
- Glucogenic – catabolism yields pyruvate or one of the . . intermediates of the citric acid cycle
→Substrates for gluconeogenesis
- Ketogenic – yields acetoacetate, acetyl CoA or acetoacetyl CoA → Not Substrates for gluconeogenesis

Question 3

What are the dietary essential amino acids?

Answer 3

Some amino acids are not synthesized in humans: these are dietary essential

-Cys and Tyr are conditionally essential: if Met is limited in the diet, Cys becomes essential; Phe is limited in the diet Tyr is essential

• Arg is also conditionally essential, its biosynthesis may not keep up with the rapidly growing individual (i.e., children who are in positive nitrogen balance)

Question 4

What is the role of liver in nitrogen metabolism?

Answer 4

• Liver is the site where most of the amino acids release their amino groups as ammonia

• NH3 is TOXIC
• Carbon skeleton is released
• NH3 is detoxified to Urea via the Urea cycle in liver
• Urea is the major end-product of N metabolism
• Urea then goes to the kidney for excretion in the urine

• Amino acid carbon skeletons are: - Used for gluconeogenesis
- Oxidized in the TCA cycle

Question 5

What is the role of the kidney in nitrogen metabolism?

Answer 5

• Urea formed in the liver is transported to the kidneys, where it is excreted in the urine
• The kidneys also excrete ammonia as ammonium ions
• Regulation of acid base balance
• Ammonia source is from glutamine (glutaminase enzyme)

Question 6

Describe the approximate distribution of urinary N-containing compounds

Answer 6

Urea-86%
Creatinine-5%
NH4+ - 3%
Other-6%
Uric acid- normally a small amount

• Other non-protein nitrogenous substances are also excreted by the kidney:
– Uric acid (end-product of purine degradation)
– Creatinine (end-product of creatine degradation) – Other
Urea is the major Nitrogen compound excreted in the urine

Question 7

How does the brush border membrane absorb amino aacids?

Answer 7

Brush border membrane absorbs amino acids by a secondary active transport mechanism.

• Na+/K+ ATPase – this is primary active transport as it is powered by ATP hydrolysis

• Three Na+ out, and two K+ in
• Establishes electrochemical gradient

• Na+ gradient harnessed by some amino acid transport systems

• Several transport systems exist, each has overlapping specificity for amino acids
• Amino acids enter into brush border cells powered by the sodium gradient, and then into the portal vein as the amino acids follow their own concentration gradient.

Question 8

What is cystinuria?

Answer 8

• Tubular reabsorption of Cystine is decreased (along with the dibasic aa ornithine, arginine, lysine) due to an inherited deficiency of the cystine transporter
• Cystine is excreted in urine
• Cystine tends to precipitate in the renal tubules (cystine stones) in the renal tract
• One of the causes of renal stones in children

Question 9

How are cystine crystals shaped?

Answer 9

hexagonal cystine crystal in urine
•shown from top

Typical hexagonal cystine crystal in urine
•shown from side

A staghorn kidney stone composed of cystine
•Typically asymptomatic (so they can get quite large)
•Very painful when it breaks off

Do not confuse these crystals with the birefringent crystals of sodium urate that is seen in the synovial fluid in patients with gout

Question 10

What is hartnup disease?

Answer 10

• Inherited defect in the transport of tryptophan - A neutral amino acid (based on side chain)

• Decreased dietary absorption of tryptophan and increased excretion of tryptophan
- Most patients are normal

• Manifestations of tryptophan deficiency

• May lead to NAD+ deficiency (pellagra)
• Only a subset of Hartnup disease patients
• Low protein diet and those lacking niacin supplementation are most susceptible

Question 11

What are the 4 D’s of pellagra?

Answer 11

• Diarrhea
• Dermatitis
• Dementia
• Death

Question 12

What is the explanation of pellagra in hartnup disease?

Answer 12

The explanation for pellagra in Hartnup disease is that niacin is not synthesized from tryptophan in sufficient amounts in these patients
Tryptophan
Many steps
Diet=
  Niacin + ATP=
 NAD

Question 13

Whaat amino acids are glucogenic?

Answer 13

Alanine
Arginine
Aspaaragine
Aspartate
Cysteine
Glutamate
Glutamine
Glycine
Proline
Serine

Question 14

Whaat nonessential amino aacid is glucogenic and ketogenic?

Answer 14

Tyrosine

Question 15

What essential amino acids are glucogenic?

Answer 15

Histidine
Methionine
Threonine
Valine

Question 16

What essential amino acids are glucogenic and ketogenic ?

Answer 16

Isoleucine
Phenylalanine
Tryptophan

Question 17

What essential aamino acids are ketogenic?

Answer 17

Leucine

Lysine