Tissue Metabolism

Question 1

Creatine

Answer 1

Forms creatine phosphate in muscle (form of energy storage)

Question 2

Glutathione

Answer 2

Protects against free radical injury (reduces peroxides)

Question 3

Purines & Pyrimidines

Answer 3

Found in nucleotides

Question 4

Sphingosine

Answer 4

Precursor of sphingolipids found in myelin (and other membranes)

Question 5

Heme

Answer 5

Incorporated into Hb

Question 6

Niacin/B3

Answer 6

NAD, NADP coenzymes for oxidation reactions

Question 7

Glycine conjugates of xenobiotic compounds

Answer 7

Inactivation, target for urinary excretion

Question 8

Xenobiotics

Answer 8

compounds that enter through the GI tract with no nutritional value but can be very toxic; enzymes responsible for detox will make the xenobiotic easier to excrete; most the of enzymes have a preferred substrate but also work on similar ones; they introduce O2 to the xenobiotic and that activates is and makes free radicals and these can cause damage within the body

Question 9

CYP 3A4/5

Answer 9

cytochrome P450 family; responsible for detox of most drugs and xenobiotic compounds; metabolize the statin drugs for example; grapefruit juice inhibits it because the grapefruit inhibits the enzymes so that the statins will accumulation which will amplify the toxic effects in that patient

Question 10

CYP2E1

Answer 10

used in ethanol detox

Question 11

Phase I Reactions

Answer 11

introduce/expose reactive groups for use in phase 2; oxidation, reduction, hydrolysis, and hydroxylation; RH to R-OH

Question 12

Phase II Reactions

Answer 12

conjugate a negatively charged group to promote excretion; conjugation, sulfation, methylation, and glucuronidation; R-OH to RSO4-

Question 13

Detox of Xenobiotics

Answer 13

The xenobiotic produces the ligands that will bind to receptor once in the cytoplasm aka nuclear receptor like a steroid or gene specific transcription factor; the TF is translated and upregulated to cause the enzyme to work

Question 14

Acetaminophen Detox in the Liver

Answer 14

UDP and glucuronyl transferase and sulfo transferase = phase II enzymes Phase I reaction – none here because already active NAPQI is a toxic intermediate that can be further modified to be excreted in urine but the problem is if the patient takes an overdose acetaminophen then the capacity of the first two enzymes are overwhelmed and there is an increase in the amount of the toxic intermediate if someone is consuming alcohol while taking this medication, then they are stimulating CYP2E1 even when taking normal dose, they are still increasing the toxic intermediate

Question 15

Signs of liver damage

Answer 15

↑ALT, AST; may have ↑[a.a.] in serum Jaundice (inefficient bilirubin glucuronidation) ↑clotting times (liver not producing clotting factors) Edema (liver not producing albumin) Hepatic encephalopathy (less urea, excess ammonia) ↑ALP and GGT may indicate some liver diseases

Question 16

Liver cirrhosis

Answer 16

Portal hypertension (HTN) Thin-walled varicies Varicies may rupture and cause bleeding into abdominal/thoracic cavity Increased ammonia in blood as bacteria metabolize blood proteins Hepatic encephalopathy

Question 17

Visceral Adipose Tissue (VAT)

Answer 17

cushions internal organs; great omentum, mesenteric, and retroperitoneal adipose tissues

Question 18

Subcutaneous Adipose Tissues (SQ)

Answer 18

between skin and muscle; deep subcutaneous and superficial subcutaneous adipose tissue

Question 19

Hormone Sensitive Lipase (HSL)

Answer 19

released when stimulated by N, NE, cortisol, and GH; releases FA into the blood carried by albumin

Question 20

Adipose in Fed State

Answer 20

Insulin promotes storage of TG (and inhibits lipolysis) Lipoprotein lipase (LPL) active in adipose and muscle tissues

Question 21

Adipose in Fasting State

Answer 21

Low insulin promotes lipolysis Lipolysis promoted by HSL activation (E, NE, cortisol, GH)

Question 22

Adiponectin

Answer 22

decreases free FA, improves lipid and glycemic profile

Question 23

Leptin

Answer 23

decreases food intake

Question 24

Interleukin - 6

Answer 24

pro-inflammatory; an increase correlates with cardiovascular disease

Question 25

MetS Criteria (3 or more)

Answer 25

Abdominal obesity TG \> 150 mg/dL HDL \< 40 mg/dL ( 130/85 Fasting blood glucose \> 100 mg/dL

Question 26

Skeletal Fiber Types: Type I, Type IIa, and Type IIb

Answer 26

Type I – Slow oxidative fibers Lots of mitochondria, myoglobin (Mb) Relatively resistant to fatigue Relatively low glycogen content Develop force slowly, maintain contractions longer Prominent in postural muscles Type IIa – Fast-oxidative fibers Functional characteristics with both Type I and Type IIb Type IIb – Fast glycolytic fibers Few mitochondria and Mb; glycogen rich Prone to fatigue- predominantly in larger limb muscles Rich in glycogen Develop greater force, contractions occur more rapidly Prominent in large muscles of limbs

Question 27

Fuels used during exercise

Answer 27

Spike of glycogen then prolonged exercise we rely on FAs then glucose; glycogen is NEVER depleted

Question 28

Creatine Kinase (CK)

Answer 28

Phosphocreatine + ADP makes Creatine and ATP

Question 29

Adenylate Kinase (AK)

Answer 29

2ADP to ATP + AMP; AMP stimulates AMP kinase to allow fatty acyl CoA to enter the mitochondria (this is done in emergencies) and prevents malonyl CoA from inhibiting fatty acyl CoA from entering mitochrondria

Question 30

Creatinine

Answer 30

creatine produced in the liver; creatinine is released from the muscle at a steady rate proportional to muscle mass and used to evaluate other molecules excreted in the urine; if elevated in the blood = impaired renal function

Question 31

Duchenne Muscular Dystrophy

Answer 31

Dytrophin is missing which connects the actin and myosin (contractile apparatus) to the sarcolemma (muscle cell membrane), which is important because the communication between the membrane and the contractile apparatus is important; when the muscle does contract the sarcolemma can bleb up and that causes problems Your muscle start to atrophy because the muscles think they are not being used (like bed ridden patient not getting physical therapy) Mostly males because females need both X chromosomes to be defected to cause this