Fate of Amino Acid: Carbon Skeleton

Question 1

____ of dietary proteins in the ____ and lumen of the ____ releases free amino acids into the bloodstream

Answer 1

Proteolysis of dietary proteins in the stomach and lumen of the small intestines releases free amino acids into the bloodstream

Question 2

Protein digestion beings in the stomach by ____ and the enzyme ____

Answer 2

Protein digestion beings in the stomach by hydrochloric acid and the enzyme pepsin

Question 3

What are three functions of hydrochloric acid in the stomach?

Answer 3

• Kill bacteria
• Denature Proteins
• Activate Pepsinogen

Question 4

Gastric Phase of Protein Digestion

Pepsin in adult stomachs is secreded as ____. It is specific for peptide bonds formed by ____ (Phe, Tyr, Trp) or ____ amino acids (aspartic acid and glutamic acid)

Answer 4

Gastric Phase of Protein Digestion

Pepsin in adult stomachs is secreded as pepsinogen. It is specific for peptide bonds formed by aromatic (Phe, Tyr, Trp) or acidic amino acids (aspartic acid and glutamic acid)

Question 5

The enzyme ____ digests milk protein (casein) in infants

Answer 5

The enzyme rennin digests milk protein (casein) in infants

Question 6

Pancreatic Phase of Protein Digestion

Occurs in the ____ with enzymes secreted from the ____

____ activates ____ to become trypsin

Trypsin then activates ____ to ____ and ____ to ____

Answer 6

Pancreatic Phase of Protein Digestion

Occurs in the small intestine with enzymes secreted from the pancreas

Enteropeptidase activates trypsinogen to become trypsin

Trypsin then activates chymotrypsinogen to chymotrypsin and proelastase to elastase

Question 7

Intestinal Phase of Protein Digestion

Intestinal enzymes are ____ and ____

The end product is ____, ____, and ____

Answer 7

Intestinal Phase of Protein Digestion

Intestinal enzymes are aminopeptidases and dipeptidases

The end product is free amino acids, dipeptides, and tripeptides

Question 8

Ammino acids are actively transported across the intestinal mucosa (needs ____, ____ pump, ____ ions, and ____)

Answer 8

Ammino acids are actively transported across the intestinal mucosa (needs carrier, Na+ pump, Na+ ions, and ATP)

Question 9

Neutral amino acid transport systems are notably important for the transport of ____ as a deficiency in this can lead to ____ disease

Answer 9

Neutral amino acid transport systems are notably important for the transport of Trp (tryptophan) as a deficiency in this can lead to Hartnup disease

Question 10

Dibasic amino acid transport systems are notably immportant for the transport of ____ as deficiencies in this can lead to ____

Answer 10

Dibasic amino acid transport systems are notably immportant for the transport of cystine as deficiencies in this can lead to cystinuria

Question 11

Hartnup’s Disease

Decreased levels of plasma ____

Urine excretion of ____

____ compounds increased

Decreased synthesis of ____ and ____ are responsible for neurological symptoms and pellegra like rash

Additonal symptoms include mental retardation and intermittent cerebellar ataxia

Answer 11

Hartnup’s Disease

Decreased levels of plasma tryptophan

Urine excretion of tryptophan

Indole compounds increased

Decreased synthesis of serotonin and pellegra are responsible for neurological symptoms and pellegra like rash

Additonal symptoms include mental retardation and intermittent cerebellar ataxia

Question 12

Cystinuria is a disorder of the ________ reabsorption of filtered ____ and ____ amino acids (ornithine, arginine, lysine)

The inability to reabsorb ____ leads to accumulation and subsequent preciptation of stones of ____ in the urinary tract

Answer 12

Cystinuria is a disorder of the proximal tubule’s reabsorption of filtered cystine and dibasic amino acids (ornithine, arginine, lysine)

The inability to reabsorb cystine leads to accumulation and subsequent preciptation of stones of cystine in the urinary tract

Note: Cystinuria is distinct from cystinosis, a rare defect in the transport of cystine out of lysosomes that results in the foramtion of cystine crystals within the lysosome and tissue damage

Question 13

Amino acids can be broken down into:

• ____ which can:
  
  • Be used for biosynthesis of AAs, nucleotides, and amines
  • Be converted to ____ and enter the urea cycle to be converted to ____ to be exreted
• Carbon skeletons which can be converted to ____ and enter the ____ cycle

Answer 13

Amino acids can be broken down into:

• Ammonia which can:
  
  • Be used for biosynthesis of AAs, nucleotides, and amines
  • Be converted to carbamyl phosphate and enter the urea cycle to be converted to urea to be exreted
• Carbon skeletons which can be converted to a-keto acids and enter the citric acid cycle

Question 14

____ amino acids give rise to pyruvate or C4 or C5 TCA cycle intermediates. All such compounds can contribute to ____

____ amino acids give rise to acetyl-CoA and excess acetyl-CoA may be converted to ________

Answer 14

Glucogenic amino acids give rise to pyruvate or C4 or C5 TCA cycle intermediates. All such compounds can contribute to gluconeogenesis

Ketogenic amino acids give rise to acetyl-CoA and excess acetyl-CoA may be converted to ketone bodies

Question 15

Amino acids ____ and ____ can be converted to fumarate

Amino acids ____, ____, and ____ can be converted to propionyl-CoA which can be converted to succinyl-CoA

Answer 15

Amino acids phenylalanine and Tyrosine can be converted to fumarate

Amino acids isoleucine, Valine, and methionine can be converted to propionyl-CoA which can be converted to succinyl-CoA

Question 16

Amino acids can be dervied from ____, ________ cycle, and the ________ pathway

Answer 16

Amino acids can be dervied from glycolysis, citric acid cycle, and the pentose phosphate pathway

Question 17

How can alanine participate in the TCA cycle?

Answer 17

Alanine can be converted to pyruvate via ALT

Question 18

How can asparagine enter the urea cycle?

Answer 18

Asparagine can be converted to aspartate via AST

Question 19

Phenylalanine and Trysosine can ultimately be converted into ____ which participates in the TCA cycle

Answer 19

Phenylalanine and Trysosine can ultimately be converted into fumarate which participates in the TCA cycle

Question 20

Isoleucine, Valine, methionine, and threonine can be converted to ____ which is converted to ____, which is converted to ____ to participate in the TCA cycle

Answer 20

Isoleucine, Valine, methionine, and threonine can be converted to propionyl-CoA which is converted to methylmalonyl-CoA, which is converted to Succinyl-CoA to participate in the TCA cycle

Question 21

What can glutamate be converted into to participate in the TCA cycle?

Answer 21

Glutamate can be converted to a-ketoglutarate to participate in the TCA cycle

Question 22

________ amino acids are those that are required to some degree in young/growing individuals or during certain illnesses or pathway defects

____ and ____ are two important examples

Answer 22

Conditionally essential amino acids are those that are required to some degree in young/growing individuals or during certain illnesses or pathway defects

Arginine and Trysosine are two important examples of conditionally essential amino acids

Question 23

The first step in amino acid degredation is the removal of ____

This occurs via an aminotransferase which requires ____ as coenzyme

Answer 23

The first step in amino acid degredation is the removal of nitrogen

This occurs via an aminotransferase which requires PLP (Vitamin B6) as a coenzyme

Note: All transamination reactions require PLP

Question 24

ALT transfers an a-amino group from ____ to ____ to form ____ and ____

(____ can be oxidatively deaminated to yield an ____ ion)

Answer 24

ALT transfers an a-amino group from alanine to a-ketoglutarate to form pyruvate and glutamate

(glutamate can be oxidatively deaminated to yield an ammonium ion)

Question 25

AST converts ____ and ____ to ____ and \_\_\_\_

Answer 25

AST converts _aspartate_ and _a-ketoglutarate_ to _oxaloacetate_ and _glutamate_

Question 26

AST and ALT are increased following damage to ____ tissue; however, ALT is more ____ specific as an increase in AST can also be seen in ____ and ____ damage

Answer 26

AST and ALT are increased following damage to _liver_ tissue; however, ALT is more _liver_ specific as an increase in AST can also be seen in _heart_ and _muscle_ damage

Question 27

Homocytinuria can be cause by (4 examples):

Answer 27

Homocytinuria can be cause by (4 examples): * Cystathionine B-synthase defect/deficiency * Methionine synthase defect/deficiency * Vitamin B6 deficiency * Vitamin B12 deficiency * Folate deficiency

Question 28

**Homocystinuia is evidenced by (2 examples):**

Answer 28

**Homocystinuia is evidenced by:** * Homocyteine in the urine * Elevated methionine and its metabolites in the blood

Question 29

**Homocystinuria results in (4 examples):**

Answer 29

**Homocystinuria results in:** * Intellectual disability * Osteoporisis * Myocardial infarction * _Lens dislocation_

Question 30

What is methyl-malonic acidemia caused by? Levels of what increase in the blood? This results in (2 examples):

Answer 30

Methyl-malonic acidemia is caused by: **Methylmalonyl-CoA mutase defect/deficiency** Levels of what increase in the blood? **Methylmalonic acid (methylmalonate)** This results in (2 examples): **Metabolic acidosis and developmental problems**

Question 31

**Oxidation of Odd Chained Fatty Acids** **Propionic acidemia** is caused by a ________ deficiency (an autosomal recessive metabolic disorder) This condition is very serious and requies a strict dietary regime and ____ supplementation Monitored by measuring ________ in the blood Presents in the early neonatal period with (4 examples):

Answer 31

**Oxidation of Odd Chained Fatty Acids** **Propionic acidemia** is caused by a _proprionyl-CoA carboxylase_ deficiency (an autosomal recessive metabolic disorder) This condition is very serious and requies a strict dietary regime and _biotin_ supplementation Monitored by measuring _propionic acid_ in the blood Presents in the early neonatal period with: * Progressive encaphalopathy * Heart/liver damage * Seizures * Delays in normal development

Question 32

**Oxidation of Odd Chained Fatty Acids** Methylmalonic aciduria can occur because of defects in ________ or in defects in ____ metabolism Increased methlmalonic acid levels are a sensitive indicator of mild ____ deficiency Treatment involves ____ restriction using formula deficient in valine, isoleucine, methionine, and threonine Infants are well at birth but become ill on protein feeding and develop lethargy, failure to thrive, muscular hypotonia, respiratory distress, and recurrent vomiting and dehydration

Answer 32

**Oxidation of Odd Chained Fatty Acids** Methylmalonic aciduria can occur because of defects in _methylmalonyl CoA mutase_ or in defects in _vitamin B12_ metabolism Increased methlmalonic acid levels are a sensitive indicator of mild _vitamin B12_ deficiency Treatment involves _protein_ restriction using formula deficient in valine, isoleucine, methionine, and threonine Infants are well at birth but become ill on protein feeding and develop lethargy, failure to thrive, muscular hypotonia, respiratory distress, and recurrent vomiting and dehydration

Question 33

The branched chain amino acids are \_\_\_\_, \_\_\_\_, and \_\_\_\_ When these enzymes are degraded in extra-hepatic tissues they share two common enzymes (2 examples): While much of the catbolism of AAs takes place in the liver, the branched chain amino acids are oxidized a primary fuels in \_\_\_\_, adipose, kidney, and brain tissues

Answer 33

The branched chain amino acids are _valine_, _leucine_, and _isoleucine_ When these enzymes are degraded in extra-hepatic tissues they share two common enzymes: * **branched-chain aminotransferase** * **branched-chain a-ketoacid dehydrogenase complex** While much of the catbolism of AAs takes place in the liver, the branched chain amino acids are oxidized a primary fuels in _muscle_, adipose, kidney, and brain tissues

Question 34

**Maple Syrup Disease** Defective \_\_\_\_\_\_\_\_ Urine has odor of \_\_\_\_\_\_\_\_ Mental and physical retardation unless patients are placed on a diet low in \_\_\_\_, \_\_\_\_, and ____ early in life BCAAs play a key role in maintaining the supply of the neurotransmitter \_\_\_\_

Answer 34

**Maple Syrup Disease** Defective _branched-chain a-keto acid dehydrogenase complex_ Urine has odor of _maple syrup_ Mental and physical retardation unless patients are placed on a diet low in _valine_, _isoleucine_, and _leucine_ early in life BCAAs play a key role in maintaining the supply of the neurotransmitter _glutamate_

Question 35

**Maple Syrup Disease** Defective \_\_\_\_\_\_\_\_, this enzyme also requires (5 examples):

Answer 35

**Maple Syrup Disease** Defective _branched-chain a-keto acid dehydrogenase complex_, this enzyme also requires: * Thiamine pyrophosphate (TPP) from thiamine (vitamin B1) * Lipoic acid * CoA from vitamin B5 * FAD from riboflavin (vitamin B2) * NAD (vitamin B3)

Question 36

**Phenylketonuria** Caused by mutations in the gene encoding \_\_\_\_\_\_\_\_ Results in a build up of ____ which gets converted to ____ and \_\_\_\_

Answer 36

**Phenylketonuria** Caused by mutations in the gene encoding \_\_\_\_\_\_\_\_ Results in a build up of ____ which gets converted to ____ and \_\_\_\_

Question 37

Phenylketonuria

Answer 37

Phenylketonuria

Question 38

**Phenylketonuria** Mutation in ________ causes ____ to accumulate in body fluids and ____ derivatives to not be made \_\_\_\_\_\_\_\_ odor in urine and sweat Treatment with ____ diet. If untreated, drastic IQ reduction

Answer 38

**Phenylketonuria** Mutation in _phenylalanine hydroxylase_ causes _phenylalanine_ to accumulate in body fluids and _tyrosine_ derivatives to not be made _Mouse-like_ odor in urine and sweat Treatment with _low phenylalanine_ diet. If untreated, drastic IQ reduction

Question 39

Deficiency in ____ also causes phenylketonuria

Answer 39

Deficiency in _tetrahydrobiopterin_ (aka (BH4/THB) also causes phenylketonuria

Question 40

A deficiency in ________ or any of the enzymes of ____ synthesis leads to hyperphenylalaninemia and decreased synthesis of ____ and \_\_\_\_

Answer 40

A deficiency in _dihydropteridine reducase_ or any of the enzymes of _BH4_ synthesis leads to hyperphenylalaninemia and decreased synthesis of _catecholamines_ and _serotonin_

Question 41

**Type II tyrosinemia** is an inborn error of tyrosine metabolism caused by a deficient ________ enzyme. Results in ____ accumulation in plasma, urine, and tissue, causing ________ and \_\_\_\_\_\_\_\_ Of note this enzyme also requires PLP (vitamin B6)

Answer 41

**Type II tyrosinemia** is an inborn error of tyrosine metabolism caused by a deficient _Tyrosine Aminotransferase (TAT)_ enzyme. Results in _tyrosine_ accumulation in plasma, urine, and tissue, causing _corneal ulcers_ and _palmoplantar hyperkeratosis_ Of note this enzyme also requires PLP (vitamin B6)

Question 42

**Alkaptonuria (Black Urine Disease)** \_\_\_\_ accumulates in urine (turns urine dark when left standing) Often benign but sclera of the eyes and ear wax may be pigmented.

Answer 42

**Alkaptonuria (Black Urine Disease)** _Homogentisate_ accumulates in urine (turns urine dark when left standing) Often benign but sclera of the eyes and ear wax may be pigmented.

Question 43

**Type I Tyrosinemia** High ____ levels. Tyrosine levels are normal or slightly elevated. Due to a deficiency in \_\_\_\_\_\_\_\_. Causes \_\_\_\_and its metabolites to accumulate in the urine. Urine has a ____ odor Treatment includes dietary resstriction of ____ and \_\_\_\_, as well as substrate reduction therapy Symptoms usually appear in the first few months of life and include **failure to thrive**, **diarrhea**, **vomiting**, **liver failure, renal tubular acidosis**, **jaundice**, and **nosebleeds**

Answer 43

**Type I Tyrosinemia** High _succinylacetone_ levels. Tyrosine levels are normal or slightly elevated. Due to a deficiency in _fumarylacetoacetate hydrolase_. Causes _fumarylacetoacetate_ and its metabolites to accumulate in the urine. Urine has a _cabbage_ odor Treatment includes dietary resstriction of _phenylalanine_ and _tyrosine_, as well as substrate reduction therapy Symptoms usually appear in the first few months of life and include **failure to thrive**, **diarrhea**, **vomiting**, **liver failure, renal tubular acidosis**, **jaundice**, and **nosebleeds**

Question 44

**Unsual Urine Odors or Colors and Their Associated AA Disorder** * Mousy/Musty * Maple Syrup * Cabbage/Rancid Butter * Black

Answer 44

**Unsual Urine Odors or Colors and Their Associated AA Disorder** * Mousy/Musty --\> PKU (Phenylalanine) * Maple Syrup --\> Maple Syrup Urine Disease (BCAA) * Cabbage/Rancid Butter --\> Tyrosinemia type I (Phe, Tyr) * Black --\> Alkaponuria (Phe, Tyr)