Rnwk1- 4-12 Biochem Nitrogen Metab In Kidney

Front 1

What goes on in the PCT?

Back 1

all the glucose reuptake occurs

Front 2

Where does and how does water get reabsorbed in kidney?

Back 2

Through transport proteins called aquaporins
- Occurs in descending loop of henle and medullary Collecting duct

Front 3

Why is the loss of a urea cycle enzyme toxic?

Back 3

Creates hyperammonemia--It backs up all the way to ammonia which has toxic effects.

Front 4

What is difference in initial vs final composition of urea in urine?

Back 4

urine has 60x concentration even though 50% reclaimed because glucose and amino acids are all reclaimed into urine causing water to flood in

Front 5

What part of nephron does water get reabsorbed from the tubules?
Where does water get reabsorbed without salt?

Back 5

PCT, descending loop of henle (not ascending), DCT, CD (water reabsorbed without salt)

Front 6

Describe the mechanism of release of anti-diuretic hormone (ADH) aka "vasopressin"...

Back 6

Supraoptic nucleus of hypothalamus- senses high blood osmoticity, releases ADH which binds to kidney receptor- which activated cAMP production.
This results in aquaporin mobilization to apical membranes,

Front 7

Where does ADH act on? (slide 18)

Back 7

aquaporin 2- vasopressive responsive aquaporin

Front 8

What area and role do the following aquaporins have?
a. AQP1
b. AQP2
c. AQP3/4

Back 8

a. kidney isoform found at apical side of PCT and descending loop
b. Apical side of CD and is ADH- responsive
c. found at the basolateral sides

Front 9

Which aquaporin is the isoform found at apical side of PCT and descending loop?
Which aquaporins are at the basolateral sides?

Back 9

AQP1

- AQP3,4

Front 10

Describe the structure of aquaporin protein

Back 10

6 transmembrane helicies and 4 subunits make up a complex through each monomer acts as a water channel

Front 11

1. In responding to high BP (aka ______?)
2. What peptide is released and what does it do?
3. Explain the mechanism of this action....

Back 11

1. (or a hypervolumic response)
2. atrial natriuretic peptide is released and decreases Na reabsorption results in increased GFR. Atrial natriuretic peptide feedbacks on the renin-angiotensin system by reducing plasma levels of renin and andosterone.
3. Involves a receptor-mediated activation of a cGMP-dependent kinase (cGK-1) that phosphorylates which inactivates the epithelial sodium channel in the PCT and CCD.

Front 12

How does aldosterone do what it does? (i.e. Na reabsorption and increased BP) (biochemically)?

Back 12

induces ENaC gene expression (DCT and CD)
1. Binds receptor
2. Activates HRE genes
3. Increased ENaC expression
4. Increased Na absorption
5. Increase BP

Front 13

Describe how renin-angiotensin system works/ how aldosterone is secreted and where each is made/ secreted...

Back 13

Renin secreted from Kidney by JGA-JG Juxtaglomerular apparatus when blood volume is low (kidney assumes its the BP)
- Renin activates angiotensinogen which was made in the liver
- Angiotensinogen activates Angiotensin I (in lung) which through ACE (angiotensin converting enzyme) turns to AngII. Angiotensin II does three main things...
1. thirst, 2. vasoconstriction, 3. signal adrenals to release Aldosterone which causes Na/water retention

Front 14

In DCT secretion of toxic metabolites and drugs what are the two key enzymes?

Back 14

OAT-1 and OCT

Front 15

Name the major nitrogenous urinary excretory products (What should rates be in g/24hrs?)
What level may we see in ammonia if the patient is acidotic? (TEST QUESTION)

Back 15

• Urea: 12‐20
• Creatinine: 1‐1.8
• Uric acid: 0.2‐0.8
• Ammonia: 0.2‐1 (up to 10 in acidosis)

Front 16

1. High urea in blood vs. urine...
2. Where is urea synthesized? Why is it made?

Back 16

1. in urine think kidney in blood think kidney
2. Made in liver to remove ammonia

Front 17

Most ammonia is removed from urea cycle made to _____ and removed in urine.
What is ammonia also removed through?

Back 17

urea
Also removed through glutamine

Front 18

What % of creatine is reabsorbed?

Back 18

0% used to find renal clearance

Front 19

What region of the kidney participates in gluconeogenesis?

Back 19

cortical region (cortex)

Front 20

How does ammonia help control blood pH?

Back 20

Ammonia (NH3) can move freely into and out of cells so it diffuses into Glomerulus
Na/H exchange occurs and H is pumped into Glomerulus and combines with NH3 to make NH4 and prevent free H's from lowering pH
-

Front 21

1. What is bicarbs role and how is it made and where?
2. What is left from original reactants?

Back 21

1. HCO3 is made from carbonic acid after H2O and CO2 combined in tubule, bicarb is able to go to blood and acts as buffer
2. - H is left from original reactants and it is pumped out into glomerulus where it combines with NH3 to make NH4 or HPO3 to make HPO4

Front 22

Name the 4 disorders of amino acid metabolism we need to know for biochem

Back 22

• PKU
• Alcaptouria
• Primary oxaluria type I
• Maple syrup urine disease

Front 23

What does PKU stand for?
What gene?
What builds up in blood?
Body effects?

Back 23

Phenylketouria
- defect in the phenylalanin hydroxylase, - PAH gene
- Phenylalanine builds up in blood and converted to phenylpyruvate (found in urine)
• Neurologic sequelae

Front 24

Explain the defect associated with Alcaptouria...
What does it cause in short term and long term?

Back 24

Enzyme defect in the tyrosine pathway
– Homogenisate oxidase
– HGD gene
• Urine oxidizes to dark color
• Later in life:
– Pigment deposits in joints (arthritis)
– Kidney and prostate stones

Front 25

What is the cause of primary oxaluria type I?
What is the gene associated with defect?
What happens with problem?

Back 25

Primary oxaluria, type I
• Defect in the transaminase that converts glyoxylate to glycine
– Alanine‐glyoxylate aminotransferase
– AGXT gene
• Glyoxylate spontaneously oxidizes to oxalate
• Oxalate crystallize with Ca2+ forming kidney stones (renal calculi)

Front 26

Describe the disease Maple Syrup urine disease....
What enzyme is involved?
What genes are involved?
What signs and symptoms does it cause?

Back 26

Maple Syrup Urine Disease
• Defect in the enzyme required for oxidative decarboxylation of BCAAs (branch chain amino acids)
– Alpha‐keto acid dehydrogenase
– Genes: BCKD, DBT, DLD
• Urine smells like burnt sugar
• Neurological complications

Front 27

What are two main amino acid transport defects?
Why would amino acid absorption defects be called a double whammy?
What do you think?

Back 27

1. hartnup disease
2. cystinuria

DOUBLE WHAMMY!- results in both kidney and small intestinal problems
- increased amino acid in urine and decrease in blood

Front 28

– Pellegra‐like symptoms
– SLC6A19
– Neutral amino acid transporter:
System name: B0

Back 28

hertnup disease

Front 29

Kidney stones
– SLC3A1; SLC7A9
– Basic amino acid transporter:
System name: B0,+

Back 29

cystinuria

Front 30

Four main types of kidney stones and describe each
What is most common type?

Back 30

• Calcium Oxalate (80-90%)
• Cystine (specific for genetic defect (cystinuria)-
• Struvite- ammonium magnesium phosphate- result of UTIs (often in women)
• Urate- formed from uric acid by product of purine metabolism

Front 31

Pneumonic for solute carrier proteins involved with defective amino acid transport diseases...

Back 31

SoLute Carrier
SLCnXm

Front 32

Explain the difference in synthesis of aldosterone and glucocorticoid?

Back 32

Aldosterone is mineralcorticoid
last two steps of synthesis uses 18-hydroxylation- then 18-oxidation