(OLD SET) Week 4 Nitrogen

Question 1

What is Positive and Negative nitrogen balance?

Answer 1

Positive: Accumulation of nitrogen in the body faster than the body can excrete it.

Negative: Nitrogen depletion- nitrogen is excreted faster than it can be taken in.

Question 2

Aminotransferase reactions do what?

Answer 2

The movement of the alpha-amino group on the amino acid

Question 3

What does glutamate dehydrogenase do?

Answer 3

Removes an alpha amino acid from glutamate.

Question 4

Can nitrogen be stored in the body?

Answer 4

No. That’s why we need a constant intake and excretion.

Question 5

Why must levels of free nitrogen in the blood be low? What amino-acids transport them?

Answer 5

Because it is toxic. That’s why they are transported by glutamine and alanine.

Question 6

How are nitrogen and urea related?

Answer 6

Ammonia is a by-product of protein being broken down in the intestines. The nitrogen from ammonia combines with other elements, such as carbon, hydrogen and oxygen, to form non-toxic urea.

Question 7

Where is urea made? Where does it go? And how does it get there?

Answer 7

Urea is made in the liver. It travels though the blood stream to the kidneys to be excreted.

Question 8

What are the two major mechanisms for controlled recycling of proteins? Describe them.

Answer 8

1. Ubiquitin-Proteosome System (UPS)
   - A tag for protein breakdown
   - Uses ATP
   - In cytosol and nucleus
2. Lysosomal degradative enzymes
   - Doesn’t require ATP
   - In cytosol only (hence typically hydrolyzing extracellular proteins.

Question 9

How does the body acquire amino acids?

Answer 9

1. de novo synthesis

2. Consumption from diet (breakdown of proteins)

Question 10

Amino acids are broken down to ______ through the glucogenic pathway or to _______ by the ketogenic pathway.

Answer 10

Amino acids are broken down to pyruvate and through the glucogenic pathway or to Acetyl CoA or acetoacetyl CoA by the ketogenic pathway.

Question 11

Describe marasmus

Answer 11

It is general starvation- a deficiency in protein and body fat

Question 12

Describe Kwashiorkor and where it generally occurs.

Answer 12

Overall calorie intake is adequate but protein is inadequate. Normally occurs in underdeveloped countries and children normal present with big bellies “ascites”

Question 13

For energy, the body uses _____ stores first, then ________ from proteins are used for gluconeogenesis and ______ is excreted via urea cycle

Answer 13

For energy, the body uses glycogen stores first, then amino acids from protein are used for gluconeogenesis and nitrogen is excreted via urea cycle

Question 14

Name the three ketone bodies

Answer 14

beta-hydroxybuterate, acetoacetate, and acetone

Question 15

In starvation, acetoacetate is an important ______ source for several tissues (except for the _____ which does not express succinyl CoA transferase)

Answer 15

In starvation acetoacetate is an important energy source for several tissues (not for liver which does not express succinyl CoA transferase)

Question 16

Why is acetoacetate important during fasting?

Answer 16

Acetoacetate is made from the break down of fatty acids and is converted to acetyl CoA by succinal-CoA transferase then it goes to the TCA.

Question 17

Describe the 4 stages of energy metabolism during starvation.

Answer 17

1. Glycogenolysis (1 day supply)
2. Gluconeogenesis (2 day supply of OAA)
3. Lipolysis and ketogenesis
4. Terminal phase (protein degradation & weakness)

Question 18

Name the three major enzymes involved in nitrogen metabolism.

Answer 18

1. Alpha-Ketogluterate: major acceptor of amino group (becomes glutamate)
2. Glutamate: donor of amino groups in biosynthesis
3. Glutamine: major transporter of nitrogen; safe way to transport otherwise toxic ammonia in blood

Question 19

What is the primary function of Aminotransferases

Answer 19

An enzyme that catalyzes the transfer reaction between an amino group on an amino acid and an α-keto acid.

Question 20

Which cofactor is considered an “energy releasing vitamin” because of its role in conversion of amino acids to alpha-ketoglutarate (a-KG) used in the TCA cycle

Answer 20

Pyridoxal phosphate (PLP)

Question 21

What reaction does Alanine aminotransferase (ALT) catalyze?

Answer 21

Glutamate + Pyruvate alpha-ketoglutarate

+ Alanine

Question 22

What reaction does Aspartate aminotransferase (AST) catalyze?

Answer 22

Glutamate + oxaloacetate Alpha-Ketoglutarate

+ Aspartate

Question 23

What is the role of glutamate dehydrogenase?

Answer 23

Conversion of Glutamate to Alpha-Ketoglutarate

Question 24

Describe the movement of and main enzymes in Nitrogen movement

Answer 24

1. Amino group is transferred to Alpha-Ketoglutarate to form Glutamate (via aminotransferases)
2. Glutamate –> Glutamine with the addition of an amide nitrogen (via glutamine synthetase)
3. Glutamine is transported to liver, where glutaminase generates glutamate and NH4+ to urea cycle
4. Glutamate –> Alpha-Ketoglutarate (via glutamate dehydrogenase) releases NH4+ to urea cycle

Question 25

What are the common causes of increased serum AST and ALT (resulting in hyperammonemia)

Answer 25

Most important cause is liver disease.

1. Non-alcoholic fatty liver disease (NAFLD)
   
   • Including steatosis, steatohepatitis, fibrosis, cirrhosis
2. Alcoholic hepatitis
3. Viral hepatitis

Question 26

What is ALT and AST used for?

Answer 26

The alanine aminotransferase (ALT) test is typically used to detect liver injury. It is often ordered in conjunction with aspartate aminotransferase (AST). When the liver is injured they are released into the blood.

Question 27

Where does the urea cycle take place?

Answer 27

Part of it takes place in the mitochondria and the other part in the cytosol

Question 28

What enzyme catalyzes the key regulatory step for the urea cycle?

Answer 28

Carbamoyl phosphate synthetase I (CPS1) turning ammonia and CO2 –> carbamoyl phosphate

Question 29

Describe what infection can contribute of hyperammonemia

Answer 29

bacterial urease generating NH4+ in the intestine

Question 30

What is uremia?

Answer 30

Is an increased urea in blood (high BUN). It occurs when urea and other waste products build up in the body because the kidneys are unable to eliminate them. Due to chronic kidney disease or acute renal failure.

Question 31

What is azotemia?

Answer 31

A high concentration of nitrogen-containing compounds in the blood (urea, creatinine, and uric acid). It is caused by a decrease in blood flow (hypoperfusion) to the kidneys

Question 32

A deficiency in any urea cycle enzyme results in congenital ______________.

Answer 32

A deficiency in any urea cycle enzyme results in congenital hyperammonemia

Question 33

What is the clinical presentation of ammonia toxicity?

Answer 33

Symptoms: tremors, slurred speech, drowsiness, vomiting, cerebral edema, blurred vision

Hepatic encephalopathy when brain swelling (due to compromised liver function)

Question 34

How can you use amino acids for energy?

Answer 34

Amino acids are broken down to pyruvate to feed into the TCA cycle.

Question 35

Why do patients with a protein calorie deficiency present with edema and ascites?

Answer 35

• In Kwashiorkor, hypoproteinemia and hypoalbuminemia lead to ascites (colloid osmotic pressure reduced and fluid goes to tissue)
• Hepatomegaly from enlarged fatty liver from carbohydrate diet

Question 36

Describe the role of ornithine transcarbamoylase (OTC) in nitrogen metabolism

Answer 36

OTC is a urea cycle enzyme that catalyzes the reaction between ornithine and carbamoyl phosphate to product citruline and thus allows a nitrogen to enter the cycle.

Question 37

What are the consequences of OTC deficiency?

Answer 37

A deficiency in OTC causes urea cycle deficiency resulting in increased serum ammonia levels. As an early enzyme in the urea cycle, OTC deficiency may cause a more severe hyperammonemia than other urea cycle enzyme deficiencies.

Question 38

Would you expect males or females to have more severe forms of OTC deficiency and why?

Answer 38

Hemizygous males would likely have the more severe form because OTC deficiency is X-linked recessive.

Question 39

Other than the severity of an OTC mutation, what would affect the clinical severity of OTC presentation in a female?

Answer 39

X-inactivation plays a big role in the presentation of OTC in a female. For example, if the X containing the normal OTC gene is inactivated in hepatic cells, the female would likely show symptoms. Depending on the pattern of X-inactivation, presentation in females ranges from asymptomatic to almost as severe as in males.

Question 40

What mechanism would be involved in conserving glucose so that it could be used for the brain with someone who is starving?

Answer 40

FA breakdown-> increase in Acetyl CoA which inhibits pyruvate dehydrogenase so less glucose converted to pyruvate destined for TCA cycle

Less Acetyl CoA goes into TCA cycle because OAA is depleted via gluconeogenesis, so Acetyl Co A is used in ketone body production

Question 41

Which acid-base disorder might develop while in starvation?

Answer 41

Ketoacdiosis will develop bc…

1. Glucose = no insulin
2. No insulin = FA beta oxidation –> ketone body formation
3. Increased ketone bodies –> acidosis from above acids, and dehydration-related decrease in tissue perfusion (lactic acid increase)

ALSO, dehydration will develop bc…
1. No insulin = Increase in plasma glucose bc glucose cannot enter the liver from the blood stream –> dehydration (due to a build up of glucose molecules in the kidneys which pulls water out preventing absorption); Increase in creatinine (due to renal failure)

Question 42

How can histamines cause increased vascular permeability leading to a runny nose associated with an allergic reaction, as well as affect gastric function?

Answer 42

• Histamine binds to receptors (H1-H4), when bound to an H2 receptor it stimulates secretion of protons transported by the H+/K+ ATPase to the gastric lumen (protons used in HCl).
• Gastric acid secretion is inhibited by a histamine H2 receptor antagonist like cimetidine, ranitidine (OTC drugs).

Question 43

Describe the role of nitric oxide in relieving angina.

Answer 43

NO binds to and activates soluble guanylate cyclase causing cGMP synthesis, which reduces amount of Ca2+ available for vascular smooth muscle contraction.

Resulting in…
Vasodilation reducing myocardial wall stress and thus decreases myocardial oxygen demand and improving oxygen delivery to cardiac muscles

Question 44

What is high amounts of alkaline phOsphatase (ALP) a sign of?

Answer 44

Biliary tract Obstruction which prevents the bile from flowing into the duodenum (AKA cholestasis)

Question 45

Hyperammonemia can be caused by a deficiency in any of the four enzymes- name them.

Answer 45

Carbomyl-Phosphate Synthetase I (CPSI)
Ornithine Trans-Carbomylase (OTC)
Argino-Succinate Synthetase (ASS)
Argino-Succinate Lyase (ASL)