Dai1-N-metabolism

Question 1

What are the 3 groups of AA’s based on side chains?

Answer 1

1) charged polar: Lys, Arg, His, & Asp, Glu
2) uncharged polar: Ser, Thr, Asn, Gln, Tyr, Cys
3) non-polar: Gly, Ala, Val, Leu, Ile, Met, Pro, Phe, Trp

Question 2

What are the essential amino acids?

Answer 2

(Pvt Tim Hall)

• -> Phe, Val, Trp,
• ->Thr, Ile, Met
• ->His, Arg*, Leu, Lys
• we synthesize at a very slow rate

Question 3

What 2 amino acids do we get from an essential amino acid?

Answer 3

• Tyrosine (from phe)

- Cysteine (from met)

Question 4

What food has a high BV (biological value)?

Answer 4

• Proteins from animal origin bc they have all essential amino acids

Question 5

Where are nonessential AA’s synthesized?

Answer 5

• Primarily in the liver

- Almost all (9/11) are made from glucose

Question 6

What is the amino acid pool?

Answer 6

• 90-100g free AAs in a steady state maintained in our body
• Sources of AAs: dietary protein, body protein breakdown, synthesis of non essential AAs
• Products of AAs: protein synthesis, N-compounds synthesis, glucose, ketone bodies
• AA can be used for E-production during starvation

Question 7

What is body protein turnover?

Answer 7

-Process in which new protein is synthesized to replace the one degraded. We degrade 1/30th of our proteins daily.

Question 8

What is Nitrogen balance?

Answer 8

N consumed in diet = N excreted (in healthy state)

Question 9

What are the 3 scenarios of negative N-balance?

Answer 9

1) Body protein breakdown (metabolic stress)
2) Inadequate dietary protein (Kwashiorkor)
3) Low quality protein ( lack essential AAs)

Question 10

What are the 2 protein degradation pathways?

Answer 10

1) ATP-dependent ubiquitin-proteosomes

2) Degradative enzymes in lysosomes

Question 11

What are the phases of protein digestion?

Answer 11

Gastric -> pancreatic -> intestinal

Question 12

How do zymogens become active enzymes?

Answer 12

• Require a biochemical change

- Ex. hydrolysis, conformational change, etc

Question 13

How are AAs absorbed?

Answer 13

• Brush border-specific active transport systems in intestines and kidney epithelium
• They all have different but overlapping specificity for AAs

Question 14

What is Cystinuria?

Answer 14

• Defective AA transporter, important in the kidney
• Low solubility of cystine –> stones
• Excretion of cystine & basic AAs in urine
• Common inherited disease
• Treatment: drinks lots of water to solubilize Cys

Question 15

What is Hartnup disease?

Answer 15

• Neutral amino aciduris
• Defective neutral AA transporter
• Failure of renal/intestinal cells to absorb neutral aa
• Skin rash, headache, psychiatric symptoms
• Treatment: high protein diet, intravenous/oral nicotinamide (niacin), tryptophan

Question 16

How is Nitrogen disposed of?

Answer 16

In the liver, a-amino groups are collected in glutamate by:

1) Transamination, released as NH4+
2) Oxidative deamination of gultamate
3) Urea cycle converts it into urea for disposal

Question 17

How can aminotransferases be used in diagnosis?

Answer 17

• Transaminases are intracellular enzymes, and they leak into blood under pathological conditions
• They are an indication of liver or muscle damage

Question 18

What is hyperammonemia?

Answer 18

• High levels of ammonia
• Can replace AAs in the diet w/ a-keto acids
• Aminotransferases will then make AAs
• Thr, Lys, Pro cannot participate in transaminations

Question 19

Why is ammonia very toxic?

Answer 19

• It can cause the reversal of oxidative deamination reaction, which depletes a-ketoglutarate, ATP, and NADH/NADPH.
• Glutamate is an excitatory neurotransmitter, which is made in reverse reaction

Question 20

What is the urea cycle?

Answer 20

• Series of rxns to convert ammonia into urea
• Complete cycle only in the liver, but partial cycle (local detox of ammonia) exist in other tissues
• Reaction in the mitochondria & in the cytosol

Question 21

What is BUN?

Answer 21

Blood Urea Nitrogen

• > High BUN: kidney problems
• > Low BUN: genetic defects in urea cycle

Question 22

How is the urea cycle regulated?

Answer 22

1) amount of enzyme

2) CPS1 activity, rate limiting step. N-acetylglutamate is a required allosteric activator.

Question 23

What is Hyperammonemia?

Answer 23

• High levels of ammonia
• Autosomal recessive defects
  1) N-acetylglutamate synthase(NAGS) deficiency
  2) CPS I deficiency

Question 24

What happens in OTC deficiency?

Answer 24

• Most common; X-linked (increased uracil and oratic acid in blood and urine)
• Episodic hyperirritability, vomiting, lethargy, protein avoidance, ataxia, coma, delayed growth and development, mental deterioration

Question 25

What is Citrullinemia?

Answer 25

• Argininosuccinate synthetasedeficiency
• Citrulline can be excreted
• Elevated blood ammonia, citrulline (40X normal), and glutamine levels, as well as urine citrulline and orotic acid, and decreased arginine
• 70% of infants with neonatal onset ASD who survive are severely mentally retarded.

Question 26

What is Argininosuccinic aciduria (ASA)?

Answer 26

• Argininosuccinate lyase (argininosuccinase) deficiency
• Argininosuccinate can be excreted
• Elevated blood ammonia, citrulline, glutamine, and urine argininosuccinic acid.

Question 27

What is Argininemia?

Answer 27

• Arginase deficiency
• Arginine can be excreted
• Extremely rare; developmental abnormalities
• Very rare disorder; Arginine secretion – takes away 2 N – less severe

Question 28

What are the sources of ammonia?

Answer 28

1) Transamination of aa’s + oxidative deamination of glutamate in the liver
2) Hydrolysis of glutamine (by glutaminase in liver, intestine, & kidneys mito)
3) Bacterial urease (intestine): urea–> ammonia
4) Direct deamination of other AAs
5) Amine oxidase (neurotransmitter metabolism)
6) Purine/pyrimidine metabolism