Biochem - E4 Review Slides

Question 1

Liver/Kidney carry out…

Answer 1

gluconeogenesis

Question 2

Liver is primary home of…

Answer 2

urea cycle

Question 3

Muscle/liver metabolize…

Answer 3

glycogen (glycogenolysis, glycogenesis)

Question 4

rbc lack malic enzyme

Answer 4

When oxidant encountered and NADP+/NADPH ratio increases, can’t generate NADPH through malic enzyme.. severe oxidative damage and red cell destruction can ensue

rbc use g6p dehydrogenase to regen NADPH

Question 5

Glucokinase vs. hexokinase

Answer 5

Glucokinase (liver/b cell) - high Km for glucose

hexokinase (ubiquitous) - low Km

Question 6

Examples of allosteric inhibition/stimulation

Answer 6

PFK1 stim via F2,6BP (glycolysis)
AcetylCoA Carboxylase stim via citrate (FAS)
Carbamoylphosphate synthetase II inhib via UDP (pyrimidine synthesis)
Glutamate dehydrogenase inhib ATP (rxn prod alpha-ketoglutarate)
Carnitine acyl transferase 1 inhib via MalonylCoA (1st prod of FAS inhibits beta-oxidation)

Question 7

Examples regulation of the amount of enzyme

Answer 7

Glucokinase increases with high CHO (glycolysis in liver)
Ornithine carbamoyl transferase increases with high protein (urea cycle)

PEPCK gene transcription increases with high cortisol (gluconeogenesis)

HMG-CoA reductase regulated by degradation/stabilization (CHL causes its degradation) (CHL synthesis)

peptidase in response to high protein diet

Question 8

Examples of covalent modification - inhibition or activation (by phosphorylation)

Answer 8

Glycogen Phosphorylase stimu by phosphorylation (glycogenolysis)
Glycogen Synthase inhib by phosphorylation (glycogenesis)

Question 9

Example of compartmental separation to regulate metabolism

Answer 9

Transport of FAs regulated by carnitine acyl transferase (CPT) 1 (beta oxidation)

Regulating acyl carnitine entering mitochondria where enzymes of beta oxidation are

Question 10

Insulin (function and major metabolic path affected)

Answer 10

• promotes fuel storage after a meal, promotes growth
• stim glucose storage as glycogen (muscle and liver) (glycogenesis)
• stim FAS and storage
• stim aa uptake and protein synthesis

Question 11

Glucagon (function and major metabolic path affected)

Answer 11

• mobilizes fuels, maintains blood glucose levels during fasting
• activates gluconeogenesis and glycogenolysis during fasting
• activates FA release from adipose tissue (cAMP –> PKA –> TAG lipase aka hormone sensitive lipase)

Question 12

Epinephrine

Answer 12

• mobilizes fuels during acute stress
• stim glucose prod from glycogen (glycogenolysis)
• stim FA release from adipose

Question 13

Cortisol

Answer 13

• provides for changing requirements over long-term

Stimulates…

• amino acid mobilization from muscle protein
• gluconeogenesis
• FA release from adipose

Question 14

Adipose vs Heart lipoprotein lipase

Answer 14

Adipose LPL –> larger Km, storage repository, allows for removal when increased fat

Muscle LPL –> smaller Km, higher affinity allows heart for access to fat for fuel even when decreased fat levels

Question 15

G-protein cycle

Answer 15

• Activation of the G protein by GDP/GTP exchange –> release of GTP-bound Gs-alpha from G-beta-gamma –> activate adenylcyclase to synthesize cAMP
• Hydrolysis allows return to inactive state (cholera toxin covalently modifies Gs-alpha to active state
• Gs –> modified by cholera toxin to keep it in active state
• Gi –> blocked by pertussis toxin to prevent inhib of adenyl cyclase (Gi –> normally inhibitory)

Question 16

Cortisol Reacts with the Glucocorticoid Receptor Found in the _______

Answer 16

Cytoplasm

Cortisol binds to specific receptor in cytoplasm, conformational change takes place, releasing receptor from hsp (chaperone) so the receptor moves to the nucleus, binds DNA, activates transcription

Exp. gluconeogenic PEPCK

Question 17

Stages of starvation (sources of glucose)

Answer 17

Absorptive (0-4 hrs): exogenous glucose

Postabsorptive (0-12hr): Glycogen, Hepatic gluconeogenesis

Early starv (16-30hr): Hepatic gluconeogen, Glycogen

Intermed starv: hepatic/renal gluconeogenesis

Prolong starv: hepatic/renal gluconeogenesis

Question 18

Use of proteins during starvation

Answer 18

Early starvation - 75 g/day

Mid/late starvation - 20g/day (less)

Question 19

Metabolite usage during fasting

Answer 19

Total amount of nitrogen excreted decreases (particularly urea).

N excreted as ammonia increases then stays higher than normal (partially to conserve cations that would be excreted along with xs KBs).

FA and KBs rise.

Question 20

Controlling Blood Glucose Levels

not dir connected to Insulin

Answer 20

a Glucosidase Inhibitors (Acarbose) Block Glucose Uptake

SGLT2 Inhibitors (Jardiance) Block Glucose Resorption in Kidney

Metformin Blocks Gluconeogenesis in Liver & Peripheral Uptake

Question 21

Controlling Blood Glucose Levels

connected to insulin secretion

Answer 21

Sulfonylureas (Glipizide) Inhibit ATP-Dependent K Channels, thus increasing insulin release from beta cells

Glinides (Replaginide) Inhibit ATP-Dependent K Channels

Incretin Analogs (Exenatide) With Extended life

DPIV Inhibitors (Sitagliptin) To Extend Incretin Life

Question 22

secretion of insulin from the pancreas

Answer 22

regulated by the ATP-sensitive potassium channel

High blood glucose and glucokinase in the cell
ATP production
closed K channels
depolarization
opening of voltage-activated calcium channels
Ca++ influx triggers exocytosis of secretory granules containing insulin

Question 23

sulfonylureas and meglitinides

Answer 23

target potassium channel of pancreatic cells

antidiabetic drugs (fo type 2)… act by increasing insulin release from the beta cells in the pancreas

Question 24

Hormones produced in the digestive tract that control insulin production/secretion

Answer 24

Incretins such as GLP-1 or GIP.
Released from cells in intestine in response to fed glucose

Close K channels via cAMP dependent signaling mechanism –> insulin release

Question 25

Type 1 DM

Answer 25

``` loss of beta-cells genetic susceptibility obsesity not usually autoimmunity: +, GAD+ (Often) Plasma insulin: little to none Insulin response: normal Fasting hyperglycemia: severe Ketoacidosis: yes Tx: insulin ```

Question 26

Type 2 DM

Answer 26

``` beta-cells initially preserved genetic susceptibility (IRS-1 mutations) obsesity common autoimmunity: usually no Plasma insulin: low to high Insulin response: usually reduced Fasting hyperglycemia: variable Ketoacidosis: not usually... Instead Hyperosmolar non-ketotic coma (HONK) (Hyperglycemic hyperosmolar synd.(HHS) ``` Tx: Diet, oral antidiabetics, insulin

Question 27

Regulation of insulin secretion

Answer 27

ATP (ATP/ADP ratio) and GLP1/GIP are “natural” regulators of the K channel. Sulfonylureas and meglitinides act on the potassium channels GLP1/GIP incretin analogues Inhibitors of DPP4 - blocks degradation of GLP1/GIP

Question 28

Insulin Signals Through a ________ Receptor

Answer 28

Insulin binds to insulin receptors on cell surface (Tyrosine Kinase receptor) --> these phosphorylate cellular targets ... - activation of Ras --> phosph/transcrip - prod of lipid PIP3.... 1. relocalization of Glut4 to promote glucose uptake (adipose/muscle) 2. activates protein phosphatase 1

Question 29

Insulin increases or decreases blood glucose?

Answer 29

decreases blood glucose by increasing glucose uptake in muscle and adipose cells.

Question 30

Insulin increases or decreases glycogen phosphorylase?

Answer 30

decreases

Question 31

Insulin increases or decreases glycogen synthase activity?

Answer 31

increases

Question 32

Insulin increases or decreases gluconeogenesis?

Answer 32

decreases, inhibits PEPCK

Question 33

Insulin increases or decreases glycolysis?

Answer 33

increases in the liver (PFK1 upregulated), so increasing acetyl CoA formation, increasing ketogeneis

Question 34

Insulin increases or decreases FAS in the liver?

Answer 34

increases (stim ACC)

Question 35

Insulin increases or decreases lipoprotein lipase?

Answer 35

increases, so increases lipid transfer to adipocytes

Question 36

Insulin increases or decreases glucose in adipocytes?

Answer 36

Increases, so increases TAG synthesis

Question 37

Insulin increases or decreases hormone-sensitive lipase?

Answer 37

Decreases, so increases lipid deposition

Question 38

Insulin increases or decreases amino acid uptake into cells?

Answer 38

Increases, so increases protein synthesis

Question 39

3 major ways that Insulin acts to reduce blood glucose

Answer 39

1. promotes glucose uptake 2. favors glycogen formation 3. inhibits gluconeogenesis

Question 40

Hypertriacylglycerolemia

Answer 40

Loss of insulin --> the lipid triad 1. elevated triglycerides 2. low HDL 3. small, dense LDL *atherogenic

Question 41

In obese people undergoing therapeutic starvation, daily excretion of urea is high in the first week and later declines. This is consistent with the fact that, as starvation continues, A. carbohydrate demands of brain and muscle increase. B. ketone body formation decreases. C. the brain begins to use amino acids for gluconeogenesis. D. the liver loses the ability to synthesize urea. E. the rate of gluconeogenesis from amino acids decreases.

Answer 41

E.

Question 42

Which of the following is not true about Type II DM? A. Most likely to be associated with adult onset B. Does not require initial treatment with insulin for most cases C. May be treated with a drug that sensitizes cells to insulin or increases insulin release D. May result in hyperosmotic non-ketotic coma E. Usually results in ketoacidosis

Answer 42

E.

Question 43

Diabetic Ketoacidosis (DKA)

Answer 43

No insulin leads to ... - uncontrolled lipolysis (hormone sensitive lipase) - failure to take up FAs (LPL) in adipose tissue Elevated FA --> synthesis of ketone bodies in liver

Question 44

hyperosmolar hyperglycemic state (HHS, HONK)

Answer 44

Type II DM | Non-ketotic, even more life-threateningly serious than DKA.

Question 45

glutamate dehydrogenase regulation

Answer 45

Inhibited by ATP/GTP, stimulated by ADP/GDP

Question 46

tx for hyperammonemia

Answer 46

- supp. benzoate or phenylbutyrate - limit protein intake, have abundance of glucose (starch) to prevent gluconeogenesis - supply arginine

Question 47

Fates of arginine

Answer 47

creatine, nitric oxide