Lecture 57 Flashcards
What are three factors involved in tissue-specific gene expression?
1) DNA methylation
2) Expression of tissue-specific transcription factors
3) Side chain modification of nuclear proteins e.g. phosphorylation and acetylation of histones
What are important functions of the kidney?
The role of the kidney in multi organ systems is illustrated by its participation in the following systems:
1) the kidney produces renin that is a part of the renin angiotensin system for the control of blood pressure & sodium balance
2) Erythropoietin is a glycoprotein produced by the kidney. It is a major regulator of erythropoiesis
3) Hydroxylation & activation of Vitamin D occurs in the kidney
What is one way of getting rid of excess protons (acidity) in the body?
Increased excretion of ammonium in the urine
What can elevated levels of creatinine indicate?
It can either indicate an excess of muscle breakdown or a greater quantity of muscle mass in an individual
How high of a fasting glucose level is indicative of diabetes?
> 125mg in blood
How much water is excreted in the urine per day?
About 1.2L
What cations and in what amounts are they excreted in the urine per day?
1) Sodium: 2-4g
2) Potassium: 1-2g
3) Ammonium: 0.4-1.0g
4) Calcium: 0.1-0.3g
5) Magnesium: 0.05-0.2g
What anions and in what amounts are they excreted in the urine per day?
1) Chloride: 4-9g
2) Sulfate: 2-5g
3) Phosphate: 2-5g
What organic compounds and in what amounts are they excreted in the urine per day?
1) Urea: 25-30g
2) Creatinine: 1.0-1.8g
3) Amino acids: 0.05-015g
4) Glucose: <150mg
What are characteristics of kidney stones?
1) About half of all kidney stones contain calcium oxalate
2) One third of kidney stones consist of calcium phosphate, magnesium ammonium phosphate, calcium carbonate or a mixture of these
3) Uric acid stones are common in gout
What are functions of the liver?
1) Capacity for regeneration
2) Regulation of nitrogen, carbohydrate & lipid metabolism
3) Formation of bile
4) Drug & hormone metabolism
5) Plasma protein synthesis
What occurs in liver regeneration?
DNA synthesis occurs after tissue injury or partial hepatectomy
What occurs in the liver during nitrogen metabolism?
The liver deaminates amino acids and converts ammonia to urea. Elevated levels of ammonia are believed to be a major factor in hepatic encephalopathy after liver damage
What occurs in the liver during carbohydrate metabolism?
The storage of glucose as glycogen and maintenance of blood glucose levels are major liver functions
What occurs in the liver during lipid metabolism?
Fatty acid synthesis, oxidation & formation of ketone bodies
What occurs in the liver during the formation of bile?
Important constituents of bile include bilirubin diglucuronide and bile salts. Gall stones consist mainly of cholesterol & bilirubin
What occurs in the liver during drug & hormone metabolism?
Much of hepatic drug metabolism can be divided into phase 1 (primarily involving cytochrome P450s in the E.R.) and phase 2 (conjugation reactions e.g. with sulfate & glucuronic acid). Ethanol is oxidized to acetaldehyde primarily by the soluble alcohol dehydrogenase but is also metabolized by the inducible cytochrome P450 2E1
What occurs in the liver during plasma protein synthesis?
Albumin & most alpha & beta globulins are synthesized in the liver
What are diagnostic tests of liver function?
1) Nitrogen metabolism: Alanine aminotransferase, Aspartate aminotransferase, Gamma glutamyl transpeptidase
2) Carbohydrate metabolism: glucose tolerance, IV galactose tolderance
3) Lipids: Cholesterol esterification
4) Bile function: Bilirubin conjugation, Alkaline phosphatase, Dye clearance
5) Drug metabolism: Hippurate excretion from benzoate
6) Plasma proteins: Blood clotting time, Albumin/globulin ratio
Describe characteristics of contractile proteins:
1) Contraction is achieved by the relative motion of thick and thin filaments. Thick filaments contain myosin. In striated muscle, the major components of thin filaments are actin, troponin & tropomyosin
2 Important concepts include: sliding filaments, steric hindrance, swinging crossbridges, ATPase & calcium signaling
Describe the power stroke of actin and myosin
1) Myosin is loaded with ATP
2) ATP-Myosin + H2O → ADP-Pi-Myosin
3) ADP-Pi-Myosin + Actin → Actin-Myosin-Pi-ADP (Power stroke occurs here)
4) Actin-Myosin-Pi-ADP → Actin-Myosin + ADP + Pi (Actin and Myosin are stuck and need to be separated for the next power stroke to occur
5) Actin-Myosin + ATP → ATP-Myosin + Actin (ATP required to release Actin-Myosin)
Describe the regulatory action of calcium in muscles
1) A nerve impulse to striated muscle results in depolarization of the outer membrane of the muscle fiber
2) The depolarization is transmitted to the sarcoplasmic reticulum and results in calcium release
3) Calcium binds to the C subunit of troponin
4) A series of conformational changes occur in troponin and tropomyosin and permit the interaction of actin with myosin
5) There is no troponin in smooth muscle. Calcium increases contraction by activation of a calcium-calmodulin-sensitive myosin light chain kinase
What are short term sources of ATP?
1) Creatine kinase catalyzes the reaction: Creatine phosphate + ADP ←→ Creatine + ATP
2) Adenylate kinase catalyzes the reaction: 2ADP ←→ ATP + AMP
What percentage of the total body ATP expenditure occurs in muscle?
40-75%
When is fatty acid oxidation used as a source of energy instead of carbohydrate metabolism?
In resting muscle, oxidation of fatty acids is a major source of energy. During exercise there is increased dependence on carbohydrate metabolism, but in very prolonged exercise fatty acid metabolism predominates
What does muscle high energy phosphate reserve consist of?
The high energy phosphate reserve in muscle consists of ATP and creatine phosphate. It will only sustain short bursts of activity
When is glycolysis important as opposed to mitochondrial oxidative metabolism?
Glycolysis is very important in fast twitch muscle whereas mitochondrial oxidative metabolism is more important in slow twitch muscles for sustained activity
Describe the Duchenne muscular dystrophy
1) Duchenne muscular dystrophy is due to a lack of dystrophin, a cytoskeletal protein
2) The dystrophin gene is X-linked
Describe Becker muscular dystrophy
1) Becker muscular dystrophy is less severe & results from an altered dystrophin molecule
Describe myotonic dystrophy
1) In myotonic dystrophy there is impaired muscular relaxation
2) The disease results from expansion of a genetic triplet repeat
3) There is autosomal dominant inheritance with increased severity in successive generations
4) Most cases are due to a defect in the gene for a protein kinase (DMPK)
Describe Limb Girdle muscular dystrophy
1) In limb girdle muscular dystrophy there is wasting of muscles proximal to the shoulders & pelvis
2) Mutations in several genes on different chromosomes may cause this phenotype
3) Most have an autosomal recessive inheritance, but some are autosomal dominant
4) Among the genes related to limb girdle muscular dystrophy are genes for sarcoglycans & calpain. Sarcoglycans are transmembrane proteins in muscle & calpain is a calcium activated protease
