Nitrogen Metabolism

Question 1

Nitrogen Metabolism

Answer 1

• Nitrogen enters the body from dietary protein
• Dietary proteins are digested to amino acids
• Nitrogen leaves the body as urea, ammonia and other products derived from amino acid metabolism

Question 2

Amino Acids

Answer 2

• Contains C, H, O, N
• amino acids are not stored in the body
• amino acids obtained by diet, de novo synthesis, protein degradation

Question 3

Amino Acid Pool

Answer 3

Come from:
- degradation of body proteins
- digestion of dietary protein
- synthesis of amino acids

Go to:
- synthesis of body proteins
- degradation of amino acids
- synthesis of N-containing compounds

Question 4

Digestion of Dietary Proteins

Answer 4

• most nitrogen in diet is consumed as protein
• proteins are too large to be absorbed by the intestine
• must be hydrolyzed to yield individual amino acids, di- and tri peptides which can be absorbed
• proteolytic enzymes are produced by the stomach, pancreas and small intestine

Question 5

Where does digestion of proteins begin?

Answer 5

The stomach

Question 6

HCl in the stomach

Answer 6

1. Acts to kill some bacteria (antiseptic)
2. Denature proteins - making them more susceptible to hydolyses by proteases

Question 7

Pepsin- acid stable endopeptidase

Answer 7

1. Secreted as an inactive zymogen- pepsinogen
2. Pepsinogen is activated to pepsin by HCl or other previously activated pepsin
3. Release peptides and amino acids from protein

Question 8

Protein digestion by pancreatic enzymes

Answer 8

• In small intestine, polypeptides are further digested by pancreatic enzymes (trypsin, chymotrypsin, elastase, carboxypeptidase)
• Enzymes secreted as inactive zymogens (trypsinogen, chymotrypsinogen) - prevent digesting own self
• Trypsinogen is activated to trypsin by enteropeptidase (trypsin activates all other proteases)

Question 9

Fate of Digested Proteins

Answer 9

• Mixture of free amino acids and short peptides taken up by intestinal cell, majority shipped out to blood to be transported to diff. tissues of body where they will be taken up by diff. tissues

Question 10

Protein Turnover

Answer 10

• Most proteins in the body are constantly being turned over (synthesized and degraded, permits removal of abnormal or unneeded proteins)

Question 11

Concentration of protein is controlled one of 2 ways

Answer 11

1. Synthesis is regulated determining conc. while degradation plays a minor role (need less, make less)
2. Synthesis is constant, and amounts of protein are controlled by regulated degradation (degradation is increased/decreased but the input is constant)

Question 12

Rate of Protein Turnover

Answer 12

• In healthy adults, total amount of protein is constant
• Rate of protein synthesis is just sufficient to replace protein that is degraded

Question 13

Rate for individual protein turnover varies widely

Answer 13

• Regulatory proteins are short lived, half-life of minutes
• Majority of proteins are long-lived, half-life of days to weeks
• Structural proteins such as collagen are stable and have half-lives measured in months to years

Question 14

Catabolism of amino acids involves

Answer 14

1. The removal of a-amino groups
2. Breakdown of the resulting C skeletons
   - don’t want to store excess amino acids since N is acidic and hazardous in body

Question 15

Catabolism of C skeletons generates

Answer 15

• Oxaloacetate, pyruvate, fumarate, acetyl CoA and succinyl CoA

Question 16

Products of catabolism of C skeletons enter into

Answer 16

• Synthesis of glucose or lipids
• Production of energy

Question 17

Glutamate is a collector of ammonia

Answer 17

• Amino groups are converted to ammonium by oxidative deamination of glutamate

Question 18

Urea cycle

Answer 18

• After transport of ammonia to liver, ammonia is converted to urea via the urea cycle

Question 19

What is urea?

Answer 19

The major disposal form of amino groups from amino acids
- once urea is formed in the liver it is transported to kidneys to be excreted in urine

Question 19

Urea Cycle Substrates

Answer 19

• CO2 combined with ammonia to form caramoyl phosphate in mitochondrial matrix (starting substrate)
• Eventually release one molecule of urea (restart cycel)

Question 20

Glucogenic amino acids

Answer 20

• Amino acids whose catabolism yields pyruvate or intermediate of TCA (oxaloacetate…),
• These intermediates are also substrates of gluconeogenesis

Question 20

Ketogenic amino acids

Answer 20

• Catabolism yields acetoacetate or one of its precursors
• These may be converted to ketone bodies but are not substrates for gluconeogenesis

Question 21

Amino Acid metabolic disorders

Answer 21

• Disruption of either synthesis or removal of amino acids can lead to disorders
• Newborn screening leads to prevention/mitigation of symptoms
• Treatments tend to be changes in diet (phenylketonuria, maple syrup urine disease, albinism)

Question 21

PKU

Answer 21

• Phenylalanine is an essential amino acid that is precursor to tyrosine (used in synthesis of melanin)
• elevated levels of phenylalanine in tissues, blood, urine
• phenylylacetate, phenylacetate and phenylpyruvate are elevated
• phenylpyruvate excreted through urine
• hypopigmentation of skin
• CNS symptoms
• treatment with diet low in phenylalanine

Question 22

Maple Syrup Disease

Answer 22

• Deficiency of enzyme branched chain a-keto acid dehydrogenase (enzyme involved in degradation of branched chain amino acids)
• elevated levels of branched-chain amino acids and their a-keto acids in the blood and urine
• severe metabolic acidosis results in maple syrup odor to urine
• treatment; diet low in protein

Question 22

Albinism

Answer 22

• Defect in tyrosine metabolism results in deficiency in production of melanin
• Partial or full absence of pigment from skin, hair, eyes