Protein Degradation And Tissue Utilization Of Amino Acids

Front 1

what are the three categories of sources of amino acids?

Back 1

de novo synthesis, dietary ingestion of protein, and intracellular protein digestion.

Front 2

what are the four categories of uses of amino acids?

Back 2

cell signaling, energy source/ degradation, protein synthesis, and synthesis of other biomolecules

Front 3

what are the two amino acids involved in cell signaling?

Back 3

glycine and glutamate

Front 4

during dietary digestion of proteins, what is released by the stomach? what does it do?

Back 4

HCl; converts pepsinogen to pepsin

Front 5

what is released by the pancreas during dietary digestion of proteins?

Back 5

bicarb, zymogens (trypsinogen, chymotrypsinogen, proelastase, and procarboxypeptidase)

Front 6

what is a zymogen?

Back 6

its an inactive form of an enzyme

Front 7

T/F
the enzymes released by the pancreas are active and start working right away.

Back 7

FALSE:
the enzymes released by the pancreas are called zymogens and they need to be activated by another enzyme.

Front 8

what is released by the endothelium cells in the duodenum during dietary digestion of protein? what is its job?

Back 8

enteropeptidase; to activate the zymogens produced by the pancreas

Front 9

what are the four active enzymes in the duodenum during dietary protein digestion?

Back 9

trypsin, chymotrypsin, carboxypeptidase, and elastase

Front 10

what are the endothelial cell enzymes that are released during dietary digestion of proteins?

Back 10

enteropeptidase, aminopeptidase, and dipeptidase.

Front 11

what is the job of the bicarb produced by the pancreas?

Back 11

to neutralize the acidity of the solution coming from the stomach and entering the duodenum.

Front 12

what is the ph level in the duodenum in comparison to the ph level in the stomach?

Back 12

duodenum= ~6
stomach = 2-3

Front 13

in what type of solution is pepsin active?

Back 13

acidic

Front 14

what enzyme produces a negative feedback on enteropeptidase?

Back 14

trypsin

Front 15

what 2 enzymes are necessary for the conversion of all of the zymogens? how many zymogens are directly converted to enzymes by each enzyme?

Back 15

enteropeptidase (1- trypsinogen to trypsin) and trypsin (3- all the others)

Front 16

what are two disorders of dietary protein that were mentioned in lecture?

Back 16

cystic fibrosis and chronic pancreatitis

Front 17

what is the inheritance of cystic fibrosis?

Back 17

autosomal recessive

Front 18

what is cystic fibrosis? what does it lead to?

Back 18

a defective chloride channel causes thickening secretions of the pancreatic duct reducing the amount of zymogens released by the pancreas. This leads to an inability to break down proteins and thus leads to malabsorption of protein.

Front 19

what does chronic pancreatitis lead to?

Back 19

ultimate destruction of zymogen producing pancreatic cells. This leads to poor protein digestion and malabsorption

Front 20

what are the symptoms and treatment for disorders of dietary digestion?

Back 20

symptoms: low protein serum and poor growth (children)
treatment: pancreatic enzyme supplemental therapy.

Front 21

what is the most important ion for uptake and transport of dietary amino acids? (ignoring tri- and dipeptides)

Back 21

Na+

Front 22

what drives the rate of uptake and transport of dietary amino acids?

Back 22

Na-K atpase pumps found on the serosal side.

Front 23

how many Na-dependent transporters are there on the lumen side of intestinal cell?

Back 23

at least six

Front 24

how are amino acids transported into the portal vein via the serosal side of the intestinal cell?

Back 24

via facilitated diffusion

Front 25

T/F
the facilitated diffusion used to transport amino acids into the portal vein is bidirectional.

Back 25

TRUE!

In times of fasting, the amino acids will enter the intestinal cell to produce energy.

Front 26

what ion is necessary for the uptake and transport of amino acids that are di and tripeptides?

Back 26

H+

Front 27

what ion is necessary as a cotransporter to deposit amino acids into circulation?

Back 27

Na

Front 28

T/F
the transporters used to bring amino acids into the intestinal cell are the same as the transporters used to deposit amino acids into circulation

Back 28

FALSE

they use the same ion, but they are different transporters

Front 29

what is Hartnups disease?

Back 29

its an autosomal recessive disorder with a defect in the absorption of neutral amino acids.

Front 30

what can lead to pellagra-like symptoms?

Back 30

lack of tryptophan (due to hartnup's disease) coupled with deficient niacin (Vit B3) in diet.

Front 31

T/F
what cannot be absorbed by the intestines can be absorbed by the kidneys.

Back 31

FALSE:
the kidneys and intestines absorb the same things, so if they are not absorbed by the intestines, then they will not be absorbed by the kidneys and will thus end up in the urine

Front 32

what are some of the symptoms of hartnups disease?

Back 32

hyperaminoaciduria of the neutral amino acids, some sensitivity to sunlight, some involuntary movement of muscle (ataxia) and eyes (nystagmus), and some tremors

Front 33

what is the treatment for hartnups disease?

Back 33

High protein and niacin-rich diet.

Front 34

what is cystinuria?

Back 34

an autosomal recessive disease that has a defect in transport of cystine and other basic amino acids (ornithine, lysine and arginine) across the brush border of the intestines and the kidneys

Front 35

what are the symptoms of cystinuria?

Back 35

cystine stones in kideys, ureter and bladder and hyperaminoaciduria (of involved amino acids)

Front 36

what is the treatment for cystinuria?

Back 36

High fluid intake and medications that increase pH of urine.

Front 37

what is lysinuric protein intolerance?

Back 37

its an autosomal recessive disease that has a defect in the transport of basic amino acids (arg, lysine, and orinithine) through the basal side of the intestinal and kidney cell

Front 38

what are the symptoms of lysinuric protein intolerance?

Back 38

hyperaminoaciduria of the basic amino acids, low plasma levels of basic amino acids and secondary hyperammonemia after meals

Front 39

what cycle do low plasma levels of basic amino acids levels affect primarily? what do they do to it?

Back 39

urea cycle. primarily lower the rate of this cycle.

Front 40

what is the treatment for lysinuric protein intolerance?

Back 40

intravenous arginine hydrochloride and nitrogen scavengers to reduce the amount of ammonium and a protein restricted, high calorie (carb) diet.

Front 41

what degradation pathway is used for misfolded or damaged intracellular proteins and turnover of intracellular proteins?

Back 41

Ubiquitin-protease pathway

Front 42

when is lysosomal degradation used in relation to protein degradation?

Back 42

for endocytosis, phagocytosis and autophagy

Front 43

what is removed in autophagy?

Back 43

organelles, protein aggregates, and intracellular pathogens

Front 44

what is the main protease involved involved in ECM turnover via lysosomes? what ion does it require for it to work?

Back 44

matrix metalloprotease; zinc

Front 45

what is removed in phagocytosis?

Back 45

pathogens (bacteria) and cell debris after apoptosis

Front 46

T/F
autophagy can be induced by eating

Back 46

FALSE:

it can be induced by starvation

Front 47

what are the major lysosomal proteases for autophagy and phagocytosis?

Back 47

cathepsins

Front 48

what are the steps involved in Ubitiqitin protease degradation?

Back 48

1st E1 (which is a ubiquitin activating enzyme) has a ubiquitin attached to it along with a sulfur group. Then E2 and 3 (ubiquitin ligases) attach themselves to E1 and then E2 exchanges the -SH group it has for the complex S-ubiquitin structure that is attached toe E1. E1 then leaves. Then enters the protein to be marked by the ubiqitin. That protein sits in the groove of the E3 and has the ubiquitin group transferred to it. Thus the protein is now marked for degradation.

Front 49

how many E1s are there? E2s? E3s?

Back 49

1; ~30; hundreds

Front 50

what determines what protein will be ubiquited?

Back 50

the composition of the E2-3 complex

Front 51

what protein is necessary for the activity of a proteasome?

Back 51

CAP proteins (ATPases)

Front 52

what is required in order for the protein to be threaded into the proteasome, but is not required for the cleavage?

Back 52

ATP

Front 53

the proteolytic subunits of the proteasome have activities that are similar to three enzymes, what are they?

Back 53

trypsin, caspace, and chymotrypsin

Front 54

what is bortezomib? what is it used to treat?

Back 54

protease inhibitor drug (blocks catalytic site of the proteasome). used to treat multiple myelomas and mantle cell lymphomas because it prevents the destruction of pro-apoptotic factors leader to cancer cell death.

Front 55

what is angelman's syndrome?

Back 55

genomic imprinting- neurological disorder that has a mutation or deletion in UBE3A gene which codes for the Ubiquitin ligase for E3. Only the maternal gene is active in brain neurons, the paternal is silenced.

Front 56

what are the symptoms of angelman syndrome?

Back 56

happy demeanor, seizures, balance and movement issues, delayed development and mental retardation, and speech impairment.

Front 57

what is Von-Hippel Lindau syndrome?

Back 57

autosomal dominant, 2 hit hypothesis. It is a deficiency in Ubiquitin ligase subunit E3 which prevents to destruction of the hypoxia inducible factor 1a (HIF1a) which causes angiogenesis. This will cause increase blood vessel formation leading to tumors.

Front 58

what are the symptoms of Von-Hippel Lindau syndrome?

Back 58

angiomatosis (little knots in capillaries), tumors in CNS, renal, adrenal gland, and endolymphatic tissue

Front 59

T/F
The body does have specialized storage for amino acids, it just isn't a lot of storage

Back 59

FALSE
the body has no specialized storage for amino acids. amino acids are stored in other forms.

Front 60

How are amino acids stored?

Back 60

80% are in skeletal muscle, and the carbon core of excess amino acids is stored as glycogen and TGs and nitrogen is secreted as urea.

Front 61

what is the primary function of the amino acid blood pool?

Back 61

to shuttle amino acids around so that they can be used for energy, deposited as waste or used for the production of biomolecules.

Front 62

what organ is the major site of amino acid metabolism? what two types of activity does it have?

Back 62

liver; catabolic and synthetic

Front 63

what does the catabolic activity of the liver do? what are the products

Back 63

converts the carbon of the amino acid to various products: TCA intermediates and pyruvate via gluconeogenesis and acetyl CoA and acetoacetate via ketone bodies

Front 64

what does the synthetic activity of the liver produce?

Back 64

glutathione, non-essential amino acids, plasma proteins, purine nucleotides and heme

Front 65

what three amino acids does the gut use for energy?

Back 65

glutathione, glutamate and aspartate

Front 66

via what vessel are most amino acids transported to the liver by?

Back 66

portal vein

Front 67

In a starved state, what is the major gluconeogenic amino acid? how is it produced both directly and indirectly?

Back 67

alanine. directly from the muscle or indirectly via the kidneys and intestines via glutamine.

Front 68

which organ in the body does not use amino acids as energy?

Back 68

brain

Front 69

what are the two purposes of glutamine in the kidney?

Back 69

energy and to balance urine pH

Front 70

what amino acid does the kidney, the liver and the intestines donate to the amino acid pool?

Back 70

alanine

Front 71

Between a fed and starvation state of the intestines, what function of the amino acid changes? which amino acids are lost?

Back 71

the source of energy changes between a fed and starvation state. The fed state has glutamate, glutamine and aspartate as sources of fuel whereas the starvation state has glutamine branched-chain.

Front 72

what is glutamine used for in the intestine?

Back 72

to synthesize orinthine and citrulline.

Front 73

which organ mainly uses alanine for purposes other than energy?

Back 73

liver

Front 74

what three types of fast dividing cells use the TCA to produce energy?

Back 74

lymphocytes, tumor cells and epithelial cells of the gut

Front 75

where is the vast majority of glutamine used? why?

Back 75

in the kidney to regulate pH. excreting NH3 as NH4.

Front 76

During sepsis, how are amino acids utilized?

Back 76

immune cells are rapidly dividing after the hepatocytes release their acute phase proteins. The rapid division of the immune cells need amino acids to synthesize more protein.