Renal--Biochem--Amino Acid Lecture 1

Front 1

What are four reasons for which proteins can be degraded?

Back 1

1) damage by free radicals
2) oxidative damage
3) misfolded
4) no longer needed

Front 2

What does nitrogen balance express?

Back 2

balance between anabolism and catabolism

Front 3

How is nitrogen balance assessed, what is a positive versus negative balance.

Back 3

comparing dietary N intake vs urinary N output. Positive balance: net storage of compounds, negative: net breakdown of stored nitrogenous compounds

Front 4

Muscle builidng does _____ nitrogen balance?

Back 4

positive

Front 5

prenancy does ____ nitrogen balance

Back 5

positive

Front 6

healing does _____ nitrogen building

Back 6

positive

Front 7

illnes/bacterial infection does _____ nitrogen balance

Back 7

negative

Front 8

uterine resorption does _____ nitrogen balance

Back 8

negative

Front 9

wounding does _____ nitrogen balance because....

Back 9

negative because constantly catabolizing the burn tissue

Front 10

describe the transamination reaction in the breakdown of amino acid (AA catabolism)

Back 10

Enzyme: transaminase
Process: amine group on random amino acid transfered to a-ketoglut to form a glutamate. This collects all amine groups onto the glutamate.

Front 11

What component is ESSENTIAL for the transamination reaction in AA catabolism?

Back 11

pyridoxal phosphate or vitamin B6. pyridoxal phosphate takes the amine off an amino acid and stores it as pyridoxamine phosphate (red) and the product is a-ketoglut (oxidized). Then the amine from the pyridoxamine phosphate combines w/ a-ketoglut to form glutamate (red) and pyridoxal phosphate (ox) regenerated

Front 12

Are transamination reactions reversible or irreversible?

Back 12

every step is reversible!

Front 13

What component is ESSENTIAL for the transamination reaction in AA catabolism?

Back 13

pyridoxal phosphate or vitamin B6. pyridoxal phosphate takes the amine off an amino acid and stores it as pyridoxamine phosphate (red) and the product is a-ketoglut (oxidized). Then the amine from the pyridoxamine phosphate combines w/ a-ketoglut to form glutamate (red) and pyridoxal phosphate (ox) regenerated

Front 14

Are transamination reactions reversible or irreversible?

Back 14

every step is reversible!

Front 15

What is the problem w/ glutamate production?

Back 15

Glutamate must be transported to liver from peripheral tissues where the amine group can be disposed. Glutamate charge, not get through memberane well so convert to glutamine which is neutral.

Front 16

What are the steps, and enzymes in the glutamate-->glutamine reaction

Back 16

1) glutamate oxidized to a-ketoglutarate and ammonia (NAD reduced) via glutamate dehydrogenase enzyme
2) second glutamate molecule reduced using ATP energy to form glutamine via glutamine synthetase enzyme

Front 17

What happens to glutamine in the liver?

Back 17

GLUTAMINASE enzyme hydrolyses glutamine to glutamate, releasing ammonia for use in the urea cycle. (Also in kidney and intestines)

Front 18

What happens to the glutamate formed in liver from glutamine?

Back 18

Enzyme: glutamate-aspartate-aminotransferase
Action: glutamate puts its amine group on oxacaloacetate which forms aspartate and a-ketoglutarate. Aspartate used in urea cycle

Front 19

What molecule acts as the "handle" in the urea cycle? Describe its overall role

Back 19

ornithine holds the amine groups which are then cleaved off as urea to regen ornithine

Front 20

Step 1 Urea cycle (enzyme name, enzyme abbreviation, subcellular localization substrate, product)

Back 20

Enzyme: carbamoyl phosphate synthetase I
abbrev: CPS I
localization: liver mitochon
Substrate: bicarb+ammonia
product: carbamoyl phosphate

Front 21

Step 2 Urea cycle (enzyme name, enzyme abbreviation, subcellular localization substrate, product)

Back 21

enzyme: ornithine trans-carbamoylase
abbrev: OTC
localization: liver mitochon
substrate: ornithine+carbamoyl phosphate
product: citrulline
** basically a condensation reaction of the two substrates w/ phosphate as leaving group

Front 22

Step 3 Urea cycle (enzyme name, enzyme abbreviation, subcellular localization substrate, product)

Back 22

enzyme: arginosuccinate synthetase
abbrev: AS
localization: cytoplasm
substrate: citrulline+aspartate
product: argininosuccinate

Front 23

Step 4 Urea cycle (enzyme name, enzyme abbreviation, subcellular localization substrate, product)

Back 23

enzyme: arginossucinase=arginosuccinate lyase
abbrev: AL
localization: cytoplasm
substrate: arginosuccinate
products: fumarate (into TCA cycle)+arginine

Front 24

Step 5 Urea cycle (enzyme name, enzyme abbreviation, subcellular localization substrate, product)

Back 24

enzyme name: arginase
abbrev: none
localization: cytoplasm
substrate: arginine
products: urea +ornithine

Front 25

What two steps in the urea cycle use energy?

Back 25

STEP 1- Uses two ATPs, the first P used to incorporate amine onto carbomyl phosphate, second phosphate acts as a leaving group
STEP 3- 1 ATP broken into AMP and 2Pi's to convert citrulline and aspartate to arginosuccinate

Front 26

What type of reactions for sure cost one ATP?

Back 26

Any reaction that creates a C-N bond

Front 27

What are two ways in which the urea cycle produces energy?

Back 27

1) Fumarate is given off in STEP 4 of urea cycle when arginine is formed from arginosuccinate and in the TCA cycle generates 1 NADH
2) The glutamate dehydrogenase reaction in the conversation of glutamate to glutamine produces NADH

Front 28

What step in the urea cycle is regulated and how?

Back 28

STEP 1- production of carbomoyl phosphate via CPS I. Buildup of glutamate converts the glutamate to N-acetyl glutamate (NAG) which allosterically activates CPS I (glutamate converted to NAG in feedforward mechanism)
2) buildup of NH3

Front 29

What do muscles utilize frequently as energy sources?

Back 29

amino acids

Front 30

What do muscles do during heavy energy demands?

Back 30

Anaerobic metabolism-->produce excess pyruvate and lactate

Front 31

What is the deal w/ alanine in muscle metabolism?

Back 31

Excess pyruvate is converted to alanine in muscle (glu aminates it) and then converted back to pyruvate in liver. The amine on alanine adds to alpha-ketoglut and forms glu. The pyruvate then forms glucose

Front 32

What are three targets for glutamine?

Back 32

intestine, kidney, liver

Front 33

What happens to glutamine in the intestine?

Back 33

It can be converted to alanine, NH4+, or citrulline

Front 34

What is the fate of the citrulline produced in the intestine?

Back 34

It is shipped intot he kidney to produce arginine

Front 35

What is the significance of arginine produced in the kidney?

Back 35

It goes into blood and is used in protein biosynthesis, DOES NOT go to liver in general

Front 36

How does the kidney compensate for acidosis?

Back 36

In acidic conditions, the glutamine in kidney is converted to ammonia which incorporates a hydronium ion to form ammonium ion which is excreted into the urine

Front 37

Why is ammonia toxic?

Back 37

Increased ammonia levels cause an increase in glutamine levels. This makes it difficult for glutamate on the post synaptic receptor to be recycled as glutamine to the pre synaptic receptor.

Front 38

What are the energetic effects of alteration of glutamate levels due to ammonia buildup?

Back 38

This is less likely, removal of ammonia requires ATP and can deplete energy levels.