Organ metabolism L62 Flashcards

1
Q

How is the gene expression regulated in Different organs?

A

Epigenetic regulation:

1) DNA methylation: decrease DNA transcription
2) Histone acetylation and Phosphorylation: increase transcription
3) Different Transcription factors in Different muscles

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2
Q

What are important functions of the kidney?

A

1) Renin which controls BP and Na metabolism though Renin-Angiotensin
2) Produces erythropoietin (glycoproteins) increase erythropeosis = making of RBC
3) Hydroxylation -> activation of Vitamin D
4) Controls the content of the ruin

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3
Q

What might happen if we have a kidney dysfunction?

A

1) Anemia
2) BP problems
3) Vit D deficiency
4) Urine composition problem (ex: Cystinuria)
5) Kidney Stones

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4
Q

What is in kidney stones

A

1/2: Ca oxalate (increased diet in oxalate causes kidney stones ex: spinach)
1/3: CaPO4 or CaCO3 or MgNH4PO4 or association
Cystein in Cystinuria
Uric Acid Stone in Gout (increased Purine metabolism -> uric acid > s) -> kidney stones and deposition in joints

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5
Q

What can the urine composition tell us?

A

1) Diabetes
2) Problems w/ amino acids/ proteins bc we should have none in the urine
3) How the pH was balances (NH4+ in the urine gets rid of H+ in the blood)
4) Creatinine comes from creatine Phosphate in muscle, more muscle mass (men), more creatinine
5) Phosphate and Sulfate reflect protein metabolism

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6
Q

What is a good kidney function test?

A

Observe levels of creatinine in the kidney

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7
Q

What are some functions of the liver?

A

1) control CHO metabolism
2) Control lipid metabolism
3) Drug and Hormone metabolism
4) Blood and plasm protein synthesis
5) Formation of Bile
6) N balance

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8
Q

What is so special about the liver as an organ

A

Ability to regenerate after a partial hepatectomy

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9
Q

How long after a complete hepatectomy would the pt die?

A

24 h

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10
Q

What does it mean if we have glucose in the urine?

A

diabetes

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11
Q

How can the kidney control pH of the blood?

A

1) gets rids of H+ as NH4+

2) Can make HCO3-

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12
Q

Why is the liver important in N balance?

A

Because the last step of the amino acid metabolism which ends up in putting the N on the urea happens in the liver

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13
Q

What happens in the N balance in the liver is dysfunctioning

A

Urea is not made

  • -> Ammonia would accumulate
  • -> Hepatic Encephalopathy/ coma due to hyperamonemia
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14
Q

How is the liver involved in the metabolism of CHO?

A

1) Glycogen storage
2) Glycogen degradation
3) Gluconeogenesis

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15
Q

How is the liver involved in the metabolism of lipids?

A

FA oxidation
FA synthesis

But FA oxidation -> Acetyl CoA
if ACoA&raquo_space; TCA
we make KB but liver cannot metabolize KB bc it lacks Acetoacetate-Succinate CoA transferase so it gives it to the muscles -> happy

Liver= Altruistic

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16
Q

How is the liver involved in lipids other than FA?

A

Cholesterol

Packaging and storing

17
Q

How is the liver involved in bile production?

A

Cholesterol
-> bile acids
Bile acids + Gly or taurine -> Bile salts which emulsify fats

bile = Bilirubin diglucunoride + Bile esters

18
Q

What diseases are involved in problems w/ Bilirubin Conjugation?

A

1) Dubin-Johnson syndrome: no removal of bilirubin
2) Crigler-Najjar: no glucunoridation of Biliirubin
- > Liver Test

19
Q

How is the liver involved in drug metabolism?

A

1) phase 1: Cytochrome P450s which are dose sensitive to the drugs and that happens in ER
2) Conjugation reaction w/ sulfate and glucorunic acid

For ethanol: metabolized by ethanol dehydrogenase which uses NAD and which is constitutive so it is not regulated
ethanol can also be metaboliszed by P450 2E1

Ethanol ->acetaldehyde -> acetate (which is tolerable)

20
Q

What happens in the liver of alcoholics?

A

We cannot upregulate ethanol dehydrogenase so the P4502E1 can help
but NAD:NADH goes up since we use ethanol dehydrogenase more
Accumulation of acetaldehyde
-> toxic
-> cirrhosis (fibrous tissue replaces hepatic tissue)

21
Q

How is liver involved in the plasma protein making?

A

1) Fibrinogen
2) Albumine (osmotic pressure)
3) Alpha and Beta Globuline
4) Prothrombine (blood clotting time)

22
Q

What happens in the event of plasma protein dysfunction?

A

1) blood clotting time extended
2) Osmotic pressure misbalance and then edema and think about Kwashiorkor when there is not enough aa to make these plasma protein

23
Q

What are the test of liver CHO metabolism?

A

1) glucose tolerance: we give a person a solution of glucose and then we see how their glycemic will be a high glycemic might be caused by DM or liver damage to store glycogen
2) IV galactose tolerance

24
Q

What is the test for liver lipid metabolism?

A

Cholesterol esterification to make cholesterol ester where OH on position 3 is esterified
Liver damage -> different levels of cholesterol:cholesterol ester

25
Q

What is the test for liver bile function?

A

1) Bilirubine conjugation
dysfunction: Crigler-Najjar and Dubin-Johnson
2) Alkaline Phosphatase
3) Dye Clearance

26
Q

What is the test for liver N balance?

A

1) Most imp Alanine Transferase
2) Aspartate Transferase (But that can also be secreted during MI so not as useful)
3) Gamma Glutamyl transpeptidase

27
Q

What is the test for liver drug metabolism?

A

conjugation og benzoate w glycine -> Hippurate which will get excreted

28
Q

What is the test for liver plasm protein function?

A

Blood clotting time, extended in liver failure

Albumine and Globuline ratios, diminished in liver failure

29
Q

What is responsible for muscle contractility

A

sliding of thick (myosin) and thin (actin, tropomyosin, troponin-not in smooth muscle)
Requires ATP

30
Q

What are sources of ATP for muscle contraction?

A

1) ATP reserve in cell

2) Creatine P + ADP –> Creatine + ATP
when muscle contracts ADP increases and that triggers the reaction towards formation of ATP
Enzyme = Creatine Kinase

3) 2ADP ATP +AMP
Enzyme = Adenylate Kinase

31
Q

What is the metabolism of a relaxing muscle?

A

FA metabolism

32
Q

What is the metabolism of a contracting muscle?

A

1) 1st glycolysis

2) then when all CHO are depleted: FA oxidation

33
Q

What is the difference between fast and slow twitch?

A

fast twitch: fast action mainly glycolysis ex: sprint or weight lifting
red twitches

slow twitch: red: a lot of mitochondria, oxidation
Long contraction: running a marathon

34
Q

Physiology of muscle contraction

A

Start at Rest
ATP attached to Myosin head
-> Myosin cannot attach to actin
ATPase activity in myosin head
ADP-Pi-Myosin
–> Actin can now attach
ADP-Pi-Myosin-Actin
The attachment of actin releases ADP and Pi= RDS
This is the power stroke where the confirmation of myosin head will change and hence cause the sliding
After Sliding, ATP attaches and Actin detaches
–> Back to rest to repeat

35
Q

Regulation of muscle contraction w/ Ca2+?

A

1) Muscle cell get nerve message depolarization
2) depolarization propagates down to Sarcoplasmic reticulum
3) Ca2+ into cytosol
4) a) In striated cells: ca binds Subunit C on Troponin
- > changes conformation
- > changes conf of tropomyosin
- > allows actin to bind to myosin

b) In smooth muscle cells:
Ca interact w ca-calmodulin sensitive myosin light chain kinase

36
Q

What diseases in the Muscle should we know?

A

1) Duschenne Muscle Dystrophy (frame shift mutation) and Becker Muscle Dystrophy.
X linked
No dystrophin present

2) Myotonic Dystrophy
Triplet repete in gene 
AD
Anticipation
No relaxation of muscle 
Prot Kinase DMPK def

3) Limb Griddle Muscle Dystrophy
locus Heterogeneity
Genes of sacroglycans (transmb port) and calpain (cal dependent protease
AR but can be AD
Wasting of muscle proximal to pelvis and shoulder