Ocpm-Amino Acid Metabolism & Urea Cycle

Front 1

What comprise the monomers that we use to make polypeptides?

Back 1

Amino acids

Front 2

How are proteins made generically?

Back 2

Transcription and translation

Front 3

How are amino acids used for energy production in our bodies?

Back 3

They contain C-C bonds which can be fed into the TCA cycle directly or indirectly.

Front 4

What must happen first before an amino acid can continue on in being used for energy production?

Back 4

The amino group must be removed, this converts it from an alpha amino acid to an alpha-keto acid, stripping off the amine group which becomes ammonia which is toxic to our bodies.

Front 5

How is ammonia removed from our bodies?

Back 5

Urea cycle disguises the ammonia and it is excreted in the urine.

Front 6

What are the two important components of Nitrogen metabolism?

Back 6

1.) Amino acid pool

2.) Protein turnover

Front 7

What is the Amino acid pool?

Back 7

The "Pool" of individual amino acids in the body excluding AA's in proteins.

They come from:
-Dietary AA's
-Tissue AA's from degradations of proteins in the body

Front 8

Describe the amino acid pool at any given time.

Back 8

Amino acid pool is approx 100g coming from:
-Body protein catab. 400g/d
-Dietary protein. 100g/d
-De Novo synth. Variable

New body protein is about 300-400g/d
AA's used for energy metabolism is variable
Gluconeogenesis
FA synthesis
CO2 & ATP
Special products. 30g/d
Porphyrins
Creatine
Purines/Pyrimidines
Neurotransmitters (GABA)

Front 9

For a 70kg male, what amount is protein?

Back 9

Approx 12kg. Of that 12kg, about 400g (3.3%) is broken down and replaced each day

Front 10

What happens to protein turnover with age?

Back 10

Synthesis of protein is greater than catabolism, same is true for anabolic situations such as weightlifting

Front 11

Some specific proteins have higher turnover rates due to shorter t1/2's, why have turnover at all?

Back 11

Protein turnover allows a cell to be adaptable to new situation/environments, Adaptability increases survival.

Front 12

Because there are protein turnover rates, there must be regulation. Turnover (degradation) is stimulated by what?

Back 12

Ubiquitin (a small protein)
-binds to protein molecule

Proteins with many Pro-Glut-Ser-Threo (PEST) sequences are rapidly degraded

Front 13

Amino acids may be used for energy, what is the typical percentage of our energy coming from Amino acids/proteins?

Back 13

20%, remembering that the primary need for proteins (AA's) is for protein synthesis.

Front 14

Americans eat approx. how much protein/day compared to the RDA?

Back 14

100g/day, RDA is 56g. We eat about 2x recommended allowance.

Front 15

What does a low protein diet lead to?

Back 15

Shortages in essential amino acids, leads to increased protein catabolism, and can lead to Kwashiorkor in extreme instances.

Front 16

Where does protein digestion begin?

Back 16

Stomach. HCL secreted by parietal cells activates pepsinogen produced by Chief cells under the direction of Gastrin and CN X (Vagus).

Front 17

Where does most protein digestion occur?

Back 17

Small intestine. Protein digestion only begins in the stomach.

Front 18

What enzymes participate in protein digestion in the small intestine?

Back 18

Pancreatic enzymes:
Trypsin
Chymotrypsin
Elastase
Carboxypeptidase

Small intestine:
Aminopeptidase

Front 19

Where is aminopeptidase found in the small intestine?

Back 19

It is found lining the mucosal cells forming the lumen of the small intestine.

Front 20

What is the function of aminopeptidase on protein structure?

Back 20

Acts on the N-terminus of proteins and clips off single AA's and short peptide fragments.

Front 21

What form are pancreatic enzymes found in prior to entering the duodenum?

Back 21

Proenzymes or zymogens which are the inactive precursors of these enzymes which if activated in the pancreas will digest the pancreatic tissue--->major problems.

Front 22

What are the inactive forms of the pancreatic enzymes?

Back 22

Trypsinogen
Chymotripsinogen
Proelastase
Procarboxypeptidase

They are cleaved by Enteropeptidase to their active forms.

Front 23

What happens to AA's and peptides that are cleaved from polypeptides?

Back 23

They are transported into the mucosal cells of the small intestine and any remaining peptide bonds are hydrolyzed. Only single AA's leave mucosal cells and enter circulation via hepatic portal circulation.

Front 24

.What is the cost to transport AA's across the mucosal cell membrane?

Back 24

AA pumps (at least 7 known) pump specific AA's across the membrane and cost ATP per AA.

Front 25

After entering circulation individual AA's lose their amine group to become alpha-keto acids, what are the two ways the amine group is removed?

Back 25

1.) Transamination (majority)

2.) Oxidative Deamination
-liver, kidney. Produces alpha keto acid and ammonia.

Front 26

What are transaminases?

Back 26

A group of enzymes specific for one or a few AA's used in transamination.

Front 27

Which AA's are not substates for at least 1 transaminase?

Back 27

Lysine & Threonine

Front 28

What is true for all Aminotransferases?

Back 28

Alpha-ketoglutarate is the amine "acceptor", products being Glutamate, and an alpha-keto acid. (The NH3 is transferred from the AA to alpha keto glutarate which becomes glutamate)

Front 29

What cofactor does Transaminase require?

Back 29

Pyridoxal-PO4 from Vitamin B6.

Front 30

What are two examples of Transaminases?

Back 30

Alanine Aminotransferase
-Also called GPT (glutamate-pyruvate transaminase). Alanine gives its NH3 to apha-KG and becomes Pyruvate.

Aspartate Aminotransferase
-Also called GDT (Glut-OAA transaminase)
-The EXCEPTION to the rule.

Front 31

Whats important to know about Alanine aminotransferase in muscle tissue?

Back 31

The reaction runs from right to left, this is creating alpha-KG and Alanine; protein breakdown occuring. High levels of Alanine in blood.

Front 32

What is the action of Aspartate aminotransferase?

Back 32

Removes the NH3 group from Glutamine (which becomes Alph-KG) and transfers it to OAA which becomes Aspartate.

Front 33

What AA is needed for Urea synthesis?

Back 33

Aspartate

Front 34

What is the function of Glutamate DH?

Back 34

Acts quickly on Glutamate produced by transaminases converting it to Alpha-KG + NH3+ (reversible rxn)

Front 35

What regulates Glutamate DH activity?

Back 35

Stimulated by:
-ADP, GDP

Inhibited by:
-ATP, GTP
*Inhibiting AA metabolism when energy supply is good.

Front 36

What are the electron carriers for Glutamate DH?

Back 36

NAD or NADP

Front 37

Plants we eat contain some D-Amino acids, how do we process these?

Back 37

Our bodies use D-Amino Acid Oxidase to convert D-AA's to Alpha-Keto acids + NH4+

Front 38

Whats important about the transaminase and glutamate dh rxns?

Back 38

They are reversible so they are employed in AA synthesis as well as catabolism.

Front 39

What are the two direct deamination rxns?

Back 39

Serine---->Pyruvate + NH4
Serine dehydratase

Threonine-->Alpha-Ketobutyral + NH4 via Threonine Dehydratase.

Front 40

How do we get rid of nitrogen?

Back 40

Consuming the ammonia (NH4) and producing Urea which can circulate in the blood and be removed in the kidneys.

Front 41

What are the nitrogenous compounds found in urine and their approx percentages?

Back 41

Urea (86%)
Creatinine (5%)
NH4+ (3%)
Other (6%)

Front 42

What are they primary forms of nitrogenous waste in birds/reptiles and fish?

Back 42

Birds/Reptiles (Uric Acid)

Fish (Ammonia, excreted all the time)

Front 43

What are the steps of the Urea cycle?

Back 43

Arginine
Ornithine
Citrulline
Argininosuccinate
Arginine + Fumarate

Front 44

What are the enzymes used in the Urea cycle?

Back 44

Arginase (produces urea)
Ornithine transcarbamylase
Argininosuccinate Synthase
Argininosuccinase

Front 45

Where is Carbamoyl-PO4 made?

Back 45

Mitochondria

Front 46

C02 + NH4 + 2 ATP + H2O------> via carbamoyl phosphate synthase yields?

Back 46

Carbamoyl-PO4
2 ADP + Pi
3 H+

Front 47

What is the rate limiting enzyme for the formation of Urea?

Back 47

Carbamoyl Phosphate synthase

Front 48

What is the rate limiting enzyme for the formation of Urea?

Back 48

Carbamoyl Phosphate synthase

Front 49

Where in the body is Urea produced?

Back 49

Liver

Front 50

What amino acid are other amino acids converted to frequently for use by the body?

Back 50

Alanine

Front 51

Why don't we want ammonia in the blood & tissues?

Back 51

It is highly toxic in small amounts. Transported as Urea or Glutamine

Front 52

Does ammonia ever accumulate "inside" the body?

Back 52

No, ammonia is immediately dumped into the urine which is technically outside the body in a storage space.

Front 53

The ketogenic amino acids are?

Back 53

Lysine
Leucine

Front 54

What is important to know about ketogenic amino acids?

Back 54

Their carbons only enter at AcCoA, can be used for Ketone production but not for gluconeogenesis (remembering pyruvate is 3 carbons) They enter as 2-C's therefore as AcCoA.

Front 55

What is important to know about Glucogenic amino acids?

Back 55

Carbons can be used for gluconeogenesis. They enter with 3 C's

Front 56

What are the Glucogenic amino acids?

Back 56

Most amino acids are, with the exception of Lysine/Leucine.

Front 57

Which are the amino acids with "mixed" catabolism (ie. Ketogenic/Glucogenic)

Back 57

Tyrosine
Isoleucine
Phenylalanine
Tryptophan
May enter as either AcCoA or other points compatible with gluconeogenesis.

Front 58

What is the mnemonic for the essential amino acids?

Back 58

PVT TIM HALL
HAL=Basic-Hist, Arg, Lys
ALL=Ketogenic only

Front 59

Which amino acids can be converted to Pyruvate and then AcCoA for TCA?

Back 59

**Alanine
Serine
Glycine
Cysteine
Threonine
Tryptophan

Front 60

Which amino acids can be converted directly to AcCoA for TCA?

Back 60

**Leucine
**Lysine
**Isoleucine
**Tyrosine
**Phenylalanine
**Tryptophan

Front 61

Which amino acids enter TCA as alpha-ketoglutarate?

Back 61

**Glutamine
**Glutamate
Proline
Arginine
Histidine

Front 62

Which amino acids enter TCA as Succynl CoA?

Back 62

Methionine
Valine
Isoleucine
Threonine

Front 63

Which amino acids enter TCA as Fumarate?

Back 63

Phenylalanine
Tyrosine

Front 64

Which amino acids enter TCA as OAA?

Back 64

Aspartate
Asparagine

Front 65

What is important about the pathways of amino acid catabolism?

Back 65

They are also reversible so that amino acid synthesis can be run in the other direction.

Front 66

What does PVT TIM HALL stand for?

Back 66

The essential amino acids. Phenylalanine, Valine, Tryptophan, Threonine, Isoleucine, Methionine, Histidine, Arginine, Lysine, Leucine.

Front 67

What is methinonine converted to during catabolism?

Back 67

Methionine to S-Adenosylmethionine (SAM)

Front 68

What is SAM (S-adenosylmethionine) important for in AA catabolism?

Back 68

Its an important CH3 (methyl) donor to the "One carbon pool" for synthesis of various compounds.

Front 69

In addition to SAM, name another important one carbon pool carrier?

Back 69

Folic acid (Folate), its activated, carbon carrying form is THF (Tetrahydrofolate)

Front 70

What are the special products produced from amino acids?

Back 70

Porphyrins
Creatine
Histamine
Serotonin
Catecholamines
Melanin

Front 71

What are porphyrins?

Back 71

Web-like structures that bind Iron (Fe2+, Fe3+) for redox rxns.

Made from Glycine, Succinyl CoA

Front 72

What is a porphyrin complexed with a metal?

Back 72

Metaloporphyrin:
Hemoglobin
Myoglobin
Cytochromes

Front 73

Where does Heme synthesis occur?

Back 73

Liver
Bone marrow

Front 74

What is the typical lifespan of an RBC?

Back 74

120 days

Front 75

Describe the breakdown of Hemes.

Back 75

Destroyed RBC-->Heme-->Biliverdin-->Bilirubin-->Bound to albumin-->Secreted in bile.

Front 76

What is the function of Heme oxigenase?

Back 76

Converts heme to biliveridin, requires (1) NADPH

Front 77

What is the function of Biliverdin reductase?

Back 77

Converts Biliverdin to Bilirubin using (1) NADPH

Front 78

What is the ultimate fate of Heme?

Back 78

It is processed and secreted into bile.

Front 79

What is jaundice?

Back 79

Higher than normal levels of bilirubin in blood

Front 80

What are the 4 types of jaundice?

Back 80

Hemolytic
Obstructive
Hepatocellular
Premature Newborn

Front 81

What is hemolytic jaundice?

Back 81

High RBC death; sickle cell, malaria

Front 82

What causes obstructive jaundice?

Back 82

Bile ducts are blocked, possibly by gallstones.

Front 83

What is Hepatocellular jaundice?

Back 83

Liver damage such as cirrhosis, hepatitis.

Front 84

Why are newborns sometimes jaundiced?

Back 84

Premature babies are frequently jaundiced because their liver is not fully developed and functional.

Front 85

What is creatine?

Back 85

A phosphate bond acceptor. Made from glycine and arginine. Its breakdown product is creatinine. Increased levels of creatine in urine=kidney malfunction.

Front 86

What is important to know about histamine as far as our amino acid lecture is concerned?

Back 86

Regulates H+ secretion by the stomach.

Results from removal of the COO- from Histidine.

Involved in allergy & inflammation rxns.

Front 87

What is important to know about Serotonin?

Back 87

Its 5-OH-Tryptamine
Made from tryptophan
Neruotransmitter in CNS & gut (enteric nervous system)

Front 88

What are catecholamines?

Back 88

Neurotransmitters of the CNS/PNS/Sympathetic autonomic systems. Made from tyrosine & phenylalanine
-Dopamine (DA)
-Norepinephrine (NE)
-Epinephrine (EPI)

Front 89

What are the breakdown products of NE and EPI? What enzymes are responsible?

Back 89

Homovanillic acid and Vanylmandelic acid.

-Monoaminie oxidase
(MAO)
-Catecholamine-O- methyl transferase
(COMT)
(Complicated)

Front 90

What is melanin?

Back 90

Skin pigment made from Tyrosine.

Albinism is absent or low