Biochem Exam 5: Aa Metabolism 1 (Protein Degradation)

Front 1

What is trypsinogen? How is it activated?

Back 1

Proenzyme excreted from pancreas into small intestine and activated to Trypsin (digestive protease) by proteolytic cleavage by enteropeptidase from GI epith cells. Also Trypsin can then form more active rest of proenzymes

Front 2

What is pepsinogen? How is it activated?

Back 2

Stomach proenzyme activated to pepsin (protease) by low pH (H+).

Front 3

What activates the following: chymotrypsinogen, proelastase, procarboxypeptidases?

Back 3

Trypsin

Front 4

How are peptides taken up from intestinal lumen & circulation?

How are they released into circulation

Back 4

Via Na co-transport. Dipeptides through H co-transport.

released via facilitated transport

Front 5

What is Hartnup disease (autosomal recessive)?
How is it treated?

Back 5

Def. in uptake of neutral/hydrophobic AAs (including Trp). If pt is also def. in B3 (niacin deficiency) = decreased NAD+ production = photosens., tremors, ataxia, nystagmus (pellagra-like) symptoms

Tx: Niacin rich diet, high protein diet.

Front 6

What AAs are elevated in the urine of patients with cystinuria.

Back 6

Cystine, Ornithine, Arginine, Lysine. ("Can Only ARGue LYS" or COAL)

Front 7

What is the cause and tx of cystinuria?

Back 7

Def. uptake of COAL at the brush border leading to cystine stones (in kidney, ureter, & bladder) and hyperaminoaciduria.
Tx: High fluid intake and meds that elevate urine pH.

Front 8

What is lysinuric protein intolerance (autosomal recessive)?
Tx?

Back 8

Defect in basal transport of basic AAs. (OAL). Patients get hyperaminoaciduria of basic AAs, low plasma basic AAs (dec urea) & secondary hyperammonemia after meals (n/v).

Tx with arginine and nitrogen scavengers to reduce blood ammonia. Also protein restr. high cal diet

Front 9

What are matrix metalloproteinases and what do they require?

What are cathepsins?

Back 9

main proteastes involved in extracellular matrix turnover, require zinc

Major lysosomal proteases.

Front 10

What is ubiquitin?

Back 10

A small protein that "marks" other intracellular proteins for degradation by proteasomes.

Front 11

What does a proteasome need to function?

Back 11

CAP proteins (ATPases) to feed the protein into protease for degradation & ATP to unfold protein & thread into proteasome core

Front 12

Why is Bortezomib (Velcade) effective in tx MM and certain lymphomas?

Back 12

It is a protease inhibitor. It is thought to stop the degradation of pro-apoptotic factors leading to cancer cell death.

Front 13

What is the result of the chromosomal deletion that occurs in Angelman syndrome?

Back 13

Codes for E3 subunit of ubiquitin ligase.

symptoms: delayed development/mental retardation, speech impairment, happy demeanor, frequent laughing, movement & balance disorders, seizures

Front 14

What is Von Hippel-Landau syndrome?

Back 14

Def. in E3 ubiquitin subunit (VHL) prevents destruction of hypoxia inducible factor (factor that promotes angiogenesis).

symptoms: Inc. incidence of tumors (angiomatosis)

Front 15

What is the fate of the vast majority of AAs in the fed state?

Back 15

*stored dynamically in functional proteins (80% skeletal muscle)

AAs are shuttled to liver and broken down. C core is used in the synthesis of glycogen and TGs. N is excreted in the urine as urea or NH4.

Front 16

How are AAs utilized during fasting?

Back 16

Skeletal muscle (esp. myosin) is broken down into AAs and sent to the liver to produce glucose through gluconeogenesis.

Front 17

What is the major glucogenic AA?

Back 17

Alanine

Front 18

Which organs provide what AAs to the AA pool?

Back 18

Kidney and intestine - alanine.
Sk. muscle - All, but mainly alanine and glutamine. Brain - glutamine.


*ala & glu most important AAs in blood AA pool

Front 19

How is glutamine used as an energy source in fast dividing cells?

Back 19

Glutamine is converted to glutamate and then to alpha-ketoglutarate (by transaminases) and fed into the TCA.

Front 20

How does usage of the AA pool shift during metabolic acidosis?

Back 20

Most glutamine is shuttled to kidney to produce NH4 (ammonia), facilitating excretion of H+ ions.
-process coupled w/ bicarbonate release to circulation

Front 21

How does usage of the AA pool shift during sepsis?

Back 21

AAs are preferentially used by the liver to produce proteins used in acute phase reactions and to immune cells for energy (glutamine is especially used here).

Front 22

obj.
List main sources of AAs

Back 22

de novo synthesis
digestion of dietary proteins
intracellular protein digestion

Front 23

obj.
List main utilization of AAs

Back 23

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

Front 24

obj.
Explain positive/negative nitrogen balance & when occur

Back 24

positive: N intake > N excretion
-during growth/pregnancy or recovery

negative: N intake < N excretion
-during illness or malnutrition

Front 25

obj.
List proteases that participate in digestion of dietary proteins

Back 25

Stomach: pepsinogen, HCl
Pancreas: HCO3-, trypsinogen, chymotrypsinogen, proelastase, procarboxypeptidases
Duodenum: aminopeptidases, dipeptidases, enteropeptidase

Front 26

obj.
explain proteolytic cascade that acts in duodeunum

Back 26

Enteropeptiidase activates proenzyme typsinogen from pancreas to trypsin, then trypsin activates rest of the proenzymes (chymotrypsinogen, proelastase, procarboxypeptidases) into chymotrypsin, elastase, & carboxypeptidase

Front 27

obj.
How does dietary AA absorption relate to reabsorption of AA in kidneys?

Back 27

1. AA absorbed through brush border of intestinal lumen (Na+ cotransport)
2. AA are released into circulation via portal vein (facilitated transport)
3. AA reabsorbed by proximal tubules of kidney (Na+ cotransport)

Front 28

If an AA cannot be absorbed by the intestine it cannot be reabsorbed from the glomerular filtrate (kidney) either, where will it go?

Back 28

AA will accumulate in urine

**thus AA absorption diseases can be detected by elevated AAs in urine

Front 29

obj.
explain lysosomal protein degradation

What type of proteins are degraded this way?

Back 29

Protease digestion & removal


-endocytosed proteins, phagocytosed particles, & autophagy (intracellular organelles)

Front 30

What do protein digestion disorders that are caused by loss of digestive proteases lead to?

How are they treated?

what are 2 examples?

Back 30

lead to malabsorption which leads to malnutrition, low serum protein levels, using albumin as a diagnostic tool, poor growth in children

treat w/ pancreatic enzyme supplement

EX; cystic fibrosis, chronica pancreatitis (alcoholism)

Front 31

How do cystic fibrosis & chronic pancreatitis result in a loss of digestive proteases?

Back 31

cycstic fibrosis: Cl- channel deficiency, leads to dried secretions blocking pancreatic duct

chronic pancreatitis: damage to pancreas, leads to loss of enzyme secreting pancreatic cells

Front 32

obj
explain ubiquitin protein degradation

Back 32

-protein "marked" w/ ubiquitin for degradation, machinery present in cytosol & nucleus will then degrade

-misfolded/damaged intracellular proteins, turnover proteins (myosin & transcription factors)

Front 33

How are AAs used in the brain (normally)?

Back 33

1. branched chain AAs (BCAAs) are transported through blood brain barrier by transporters
2. in astroglial cells, amino group of BCAAs undergoes transamination to make glutamate, which is converted to glutamine
3. glutamine is transported to neurons & converted back to glutamate & GABA