Amino Acid Metabolism Flashcards Preview

Medical Biochemistry > Amino Acid Metabolism > Flashcards

Flashcards in Amino Acid Metabolism Deck (39):
1

What is the Amino Acid Pool and where do these AAs come from?

The come from Protein turnover from misfolded proteins being broken down, digested food that has been absorbed by small intestine, and de novo synthesis.

2

What are proteolytic enzymes? Give specific examples of Exopeptidases and endopeptidases.

Proteolytic enzymes are enzymes that cleave proteins. Based on the specific part, there are exopeptidases and endopeptidases.

Exopeptidases--> cleave on either the N terminus exopeptidases or the C terminus exopeptidases.
N-terminus: aminopeptidases
C-terminus: carboxypeptidases

3

What are lysosomes and at what pH are they activated?

Lysosomes are intracellular organelles that degrade protein via hydrolysis. They are the most active at pH=5 and inactive at pH=7.

4

What are the different types of methods that a lysosome will have to try and target degradable proteins?

They have non-selective and selective means:

Non-selective: macroautophagy, microautophagy, charperone-mediated autophagy

Selective: via Endocytosis and MVB Pathway

5

What are the different methods that a cell will use to degrade older proteins or mis-folded proteins?

1.) lysosomal degradation
2.) proteosome degradation

6

What is the proteosome and how does it work?

The proteosome is a large protein complex consisting of 19s, 20s, 19s subunits ( 19s= regulatory, 20s= catalytic).

The process by which it works is through electrostatic interaction between 19s subunit with UBIQUITIN protein to bind to the proteosome for degradation.

7

What is the connection between the proteosome and the Urea Cycle? Other catabolic processes?

The proteosome will break down proteins to the basic sub-units: a.) NH3 b.) carbon skeleton c.) Ubiquitin

Carbon Skeleton--> TCA cycle, Glycolysis, etc.

NH3--> Pushed out via the Urea Cycle by using CPSI shuttle in the mitochondria that helps create carbamoyl-P.

**That is added to ornitate--> citrulline-->aspartosuccinate--> arginine (fumarate leaves)--> ornithine (Urea leaves)

8

What amino acid residue helps link Ubiquitinated protein to the proteosome?

Lysine residues via polar, electrostatic interactions

9

what happens in MACRO-LEVEL extracellular proteolytic cleavage?

-proteolytic enzymes secreted as needed based on what the organism eats (small intestine digestion)

- usually secreted in inactive zymogen forms:
small intestine lumen (enterocytes) that secrete peptidases--> cleavage of trypsinogen to trypsin enzyme
--> leads to the breakdown of a lot of other proteolytic enzymes like chemotripsinogen--> chemotripsin

10

Tell me all of the Essential Amino Acids?

PVT TIM HALL

Phenylalanine
VALINE**
Threonine

Tryptophan
ISOLEUCINE**
Methionine

Histidine
Arginine**
Leucine
Lysine

11

Tell me all the ketogenic amino acids? (2)

Leucine & Lysine

12

Tell me all the ketogenic & glucogenic amino acids? (5)


Tryptophan, Tyrosine, Phenylalanine, Isoleucine, Threonine
(All "T" Amino acids, All "aromatic" amino acids, and Isoleucine)

13

What is oxidative deamination and where does it take place?

Oxidative deamination is the conversion of an amide to a ketone via the use of Glutamate Dehydrogenase (GDH) which converts:

Glutamate--> Alpha-KG + NH3


Oxidative Deamination is the step used in the liver to create free standing NH3 to enter Urea Cycle. First transamination of unwanted AA occurs, followed by formation of its base keto-acid.

NH3--> CPSI--> Carbamoyl-P
carbamoyl P enters Urea cycle and binds with ornithine

14

What is the name of the cofactor essential for transaminase enzymes?

Pyrridoxyl- 5'-phosphate which is a derivative of Vitamin B6

15

What is the clinical relevance of ALT (Alanine Transaminase) and AST (aspartate transaminase)?

ALT and AST are specific transaminases that are used to determine liver disease or liver damage. The increase in the level of these transaminases suggest increased permeability in hepatocytes--> release of Transaminase Proteins.

16

What are the names of AAs in the Alpha-ketoglutarate family?

Glutamate, Glutamine, Proline, Arginine,

17

What are the names of the AAs in the oxaloacetate family?

Aspartate, Asparagine, Methionine, Threonine, Isoleucine, Lysine

18

What are the names of the AAs in the pyruvate family?

Alanine, Valine, Leucine

19

What are the names of the AAs in the Ribulose-5-phosphate family?

Histidine

20

What are the names of the AAs in the E-4-P + PEP family?

Tryptophan, Tyrosine, Phenylalanine

21

What are the names of the AAs that are made from the 3-PG family?

Glycine, Cysteine, Serine

22

What are the names of the AAs that feed into the glucogenic pathway for Succinyl-CoA?

Methionine, Valine, Isoleucine

23

What are the names of the glucogenic AAs that fall into alpha-ketoglutarate intermedicate?

Glutamine, Proline, Arginine, Histidine*

24

What are the names of the glucogenic AAs that fall into OAA?

Arginine, Aspartate

25

What are the names of the glucogenic AAs that fall into the Fumarate intermediate?

Tryptophan, Phenylalanine, Aspartate*

26

What is homocystinuria and what causes it? What are the clinical symptoms of it and how can you treat it?

Homocystinuria is a methionine degradation pathway problem. The disorder is accompanied by enzyme defficiency with cystathione Beta- Synthase, Cobalamin (Vitamin B12) deficiency, or homocysteine methyl transferase enzyme issues.

Sx: Megoblastic Anemia

Tx: Give Pyrridoxin Vitamins, DECREASE methionine in diet, give betaine drug to methylate homocysteine back to methionine


27

What are the branched chain AAs?

Valine, Leucine, Isoleucine (LIV)

28

What is Maple Syrup Disorder?

Autosomal recessive Disorder
Caused by: Branched Chain Alpha-Keto Acid Dehydrogenase

Sx: Maple syrup odor in urine from the alpha-keto acids in blood and urine; metabolic acidosis, swelling of the brain, coma

Tx: Dietary Leucine Restrictions
Liver Transplant

29

What is Phenylketonuria? What are the by-products of it? What does it cause? How do you treat it?

Phenylketonuria is a disorder that is caused during the degradation of Phenylalanine in the blood to Tyrosine.

Affected Enzyme: Phenylalanine Hydroxylase Enzyme

Phenylalanine accumulation leads to:
Phenylacetate + phenyllactate in the blood

SX: low phenylalanine tolerance, MUSTY ODOR (skin, breadth, urine)

***BIGGEST PROBLEM--> NT Disruption and blocks AA transport in the brain--> brain swelling (encephalopathy)

DX: POST-PARTITION GUTHRIE TEST (Test right after mother gives birth 24-48 hrs later)

TX: R-tetrahydrobioptein, Decrease GI uptake of Phenylalanine via drugs



30

What are the important derivatives from Tryptophan AA?

Derivatives of Tryptophan include:
1.) Serotonin Production
2.) Melatonin Production (need Serotonin for Melatonin)

Problems: Tryptophan deficiency leads to Carcinoid Tumors

31

What are the Tyrosine derivatives?***

Tyrosine Derivatives:

Triiodothyronine (T3)
Thyroxine (T4)
Problem: Thyroglobulin Problem
Complications: Grave's Disease, Hyper/Hypothyroidism

Melanin
Problem: Lack of Melanin Production due to Tyrosine Def.
Complication: Albinism

Dopamine
Problem: Cannot form Dopamine and release in Substantia Nigra
Complication: Parkinson's Disease

Norepinepherine Production**


32

How does the brain remove excess NH3 ions?

The brain removes NH3 ions via Glutamine Synthase/Glutamine Synthetase:

NH3+ Glutamate--> Glutamine (Glutamine Synthase)

***The glutamine goes into the blood where it enters hepatic portal system and goes through the transamination in the liver and oxidative deamination via glutamate into Urea Cycle

33

What are the means of which NH3 is removed from the other tissues like the muscle and other organs (besides Brain)?

Alanine (ALA transaminase) + Glutamine (Glutamine Synthase)

34

what is the means by which muscle tissues remove excess NH3 ions?

The removal of NH3 occurs through ALA transaminase reaction that uses a pyruvate molecule and another AA to convert to Alanine + KETO ACID (corresponding to AA1).

35

What is the general mechanism of the Urea Cycle?

The Urea Cycle will first form:
1.) Transamination of either Alanine/Glutamine to produce a molecule of Glutamate

2.) Glutamate will lose its NH3 by oxidative deamination

3.) Carbamoyl P Synthetase I(CPS I) in Mitochondria will
take up the NH3 to create Carbamoyl-P

4.) Then carbamoyl-P will be added to Ornithine which will be filtered out into cytosol in the form of fumarate, urea, etc.

5.) Ornithine is Regenerated

36

What is the problem with free standing NH3(g) that is worse than NH4+ Ion?

It can freely cross the blood/brain barrier. It will cause:

encephalopathy
pH imbalance
cerebral edema
intracranial hypertension

DECREASE [glutamate] which is an important neurotransmitter which leads to CNS depression.

DECREASE [Alpha-Ketoglutarate] because all of the alpha ketoglutarate will be in the form of either GLUTAMATE/GLUTAMINE---> TCA CYLCE SUPPRESSION

37

What happens when you eat a high protein diet?

Urea cycle activity increases, 20-30% of urea production will be in the gut--> feeding those bacteria in gut

38

What is Creatine?

Creatine is a protein reservoir for Phosphate groups to be replenished in times of physical work.

39

What AAs make up Creatine?

Glycine, Arginine, Methionine (GAM)

Side Note: CK-MB form found in MI/heart attack cases in the blood