Glycolysis and Pyruvate Dehydrogenase (Biochem) Flashcards Preview

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Flashcards in Glycolysis and Pyruvate Dehydrogenase (Biochem) Deck (81)
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1

in which cells does glycolysis occur?

- glycolysis occurs in all cells
- in RBC, glycolysis represents the ONLY energy-yielding pathway available (bc they don't have mito)

2

normal blood glucose in mM?

- normal = 4-6 mM
- 70-110 (or 60-100) mg/dL

3

Why do we give Potassium Chloride to a patient in DKA?

- because we're also giving insulin, and insulin causes K to be absorbed by the cells.

- Insulin causes Potassium to shift into the cells thereby decreasing the extracellular K level.
- That's why insulin is used in the treatment of hyperkalemia.
- Level of Potassium in the serum also affects insulin secretion from the pancreas.
- Because the beta cells have an ATP dependent K channel which, when closed, leads to retained K inside the beta cell which favors depolarization thereby enhancing Calcium mediated release of secretory granules.
- Therefore, in hyperkalemia more K will enter the beta cell and insulin secretion will increase
- and conversely in hypokalemia the K ions are more likely to leave the beta cell and so insulin secretion will decrease.

4

the first steps in glucose metabolism in any cell are:

- transport across the membrane
- and phosphorylation by kinase enzymes inside the cell to prevent it from leaving via the transporter

5

most of the carbs in food are in complex forms like:

- starch: amylose and amypectin
- disaccharides: sucrose and lactose
- only a very small amount of the total carbs ingested are monosaccharides

6

What begins to digest carbs in the mouth?

- in the mouth, secreted salivary amylase randomly hydrolyzes the starch polymers to dextrin ( less than 8-10 glucoses)
- upon entry into the stomach, the acid pH destroys the salivary amylase

7

What breaks down dextrin? and where does this occur?

- in the intestine, dextrin are hydrolyzed to the disaccharides maltose and isolates
- disaccharides in the intestinal brush border complete the digestion process

8

Maltase function

Maltase cleaves maltose to 2 glucoses

9

isomaltase function

isomaltase cleaves isomaltase to 2 glucoses

10

lactase function

lactase cleaves lactose to glucose and galactose

11

sucrase function

sucrase cleaves sucrose to glucose and fructose

12

- how does glucose get into the mucosal cells?
- is this active or passive transport?

- the sodium/glucose transporter moves glucose into mucosal cells
- this is an Active Transporter
- glucose entry into most cells is concentration driven
- it is INDEPENDENT OF SODIUM!!!!!!!

13

What is the normal concentration of glucose in peripheral blood?

4-6 mM or 70-110 mg/dL

14

Where is the GLUT 1 transporter found?
- kinetics

- GLUT 1 and GLUT 3 mediate basal glucose uptake in most tissues, including brain, nerves and RBC
- Their high affinities for glucose ensure glucose entry even during periods of relative hypoglycemia
- at a normal glucose concentration, GLUT1 and GLUT 3 are at Vmax.

15

- GLUT 2 is found where?
- kinetics?

- GLUT 2 is a low-affinity transporter, found in hepatocytes
- after a meal, portal blood = rich in glucose
- GLUT 2 captures the excess glucose primarily for storage
- when the glucose concentration drops below the Km for the transporter, much of the remainder leaves the liver and enters the peripheral circulation
- in the beta islet cells of the pancreas, GLUT 2 (along with glucokinase) serves as the glucose sensor for insulin release
- Bc both GLUT 2 and glucokinase have high Km values for glucose, glucose is transported and phosphorylated via 1st order kinetics (directly proportional to glucose concentration in the bloodstream)

16

GLUT 4 translocation to the cell membrane in skeletal muscle is stimulated by??

- exercise
- this effect, which is INDEPENDENT OF INSULIN, involves a 5' AMP-activated kinase

17

Where is the GLUT 3 transporter found?

- GLUT 1 and GLUT 3 mediate basal glucose uptake in most tissues, including brain, nerves and RBC

18

- Where is GLUT 4 found?
- How does it respond?

- GLUT 4 is in adipose tissue and muscle
- it responds to the glucose concentration in peripheral blood
- the rate of glucose transport in these 2 tissues is increased by insulin, which stimulates the movement of additional GLUT 4 transporters to the membrane
- decreased insulin decreases the # of plasma membrane GLUT 4 transporters by endocytosis of the transporter into cytoplasmic vesicles.
- increased insulin increases the # of plasma membrane GLUT 4 transporters through fusion of the cytoplasmic vesicles containing the membrane-bound GLUT 4 with the plasma membrane.

19

What signals insulin release in the beta islet cells of the pancreas?

- the GLUT 2 transporter and glucokinase serves as the glucose sensor for insulin release from the beta islet cells of the pancreas
- insulin secretion by the pancreatic beta cells is biphasic
- glucose stimulates the first phase (within 15 mins) with release of preformed insulin
- the 2nd phase (several hours) involves insulin synthesis at the gene level

20

GLUT 1:
- tissues
- Km, Glucose
- functions

- most tissues (ESP BRAIN and RBC)
- Km, glucose: approx 1 mM
- f(x): basal uptake of glucose

21

GLUT 2:
- tissues
- Km, Glucose
- functions

- liver, pancreatic beta cells
- Km, glucose: approx 15 mM
- f(x): uptake and release of glucose by the liver beta cell glucose sensor

22

GLUT 3:
- tissues
- Km, Glucose
- functions

- most tissues
- Km, glucose: approx 1 mM
- f(x): basal uptake

23

GLUT 4:
- tissues
- Km, Glucose
- functions

- skeletal muscle, adipose tissue
- Km, glucose: approx 5 mM
- f(x): insulin-stimulated glucose uptake; stimulated by exercise in skeletal muscle

24

Although basal transport occurs in all cells indepdently of insulin, the transport rate ____ in adipose tissue and muscle when insulin levels ____

Although basal transport occurs in all cells indepdently of insulin, the transport rate INCREASES in adipose tissue and muscle when insulin levels RISE

25

Why does the transport rate of glucose into muscle cells INCREASE when insulin levels increase?

- the transport rate of glucose into muscles increases when insulin levels increase bc:
- muscle stores excess glucose as glycogen

26

Why does the transport rate of glucose into adipose tissue INCREASE when insulin levels increase?

- the transport rate of glucose into adipose tissue INCREASES when insulin levels increase bc:
- adipose tissue requires glucose to form dihydroxyacetone phosphate (DHAP) which is converted to glycerol phosphate and is used to store incoming FA as TG
- TGL = 3 FA attached to glycerol.

27

insulin ____ PFK-2 in the liver by _____

insulin stimulates PFK-2 in the liver by dephospho rylation

28

What 3 enzymes in Glycolysis are rate-controlled and catalyze irreversible steps?

*Because of these 3 enzymes, Glycolysis is Irreversible, when the liver produces glucose, different reactions and therefore different enzymes must be used at these points!

1. Hexokinase (all tissues) aka Glucokinase (in liver)
- Glucose --> Glucose 6P
- Mg2+ cofactor; requires ATP --> ADP
- Glucose 6P downregulates
- insulin stimulates

2. PFK-1
- Fructose 6P --> Fructose-1,6 bis P
- ATP --> ADP
- AMP stimulates
- ATP, citrate inhibit/downregulate

3. Pyruvate Kinase
- Phosphoenolpyruvate (PEP) --> Pyruvate
- ADP --> ATP
- Fructose 1, 6 bis P is an allosteric activator of forward reaction (of pyruvate kinase)

29

Pyruvate Kinase Deficiency
- Findings

- 2nd MC genetic deficiency that causes hemolytic anemia
- AR
- (#1 MCC = G6PD deficiency)
* Causes:
- chronic hemolysis --> hemolytic anemia
- increased BPG --> lower-than-normal O2 affinity of HbA
- no heinz bodies (heinz bodies are more characteristic of G6PD deficiency)
- results from a partial enzyme defect

30

Effects of 2,3 bisphosphoglycerate on the O2/Hb curve

- RBC have bisphosphoglycerate mutase which converts 1,3 BPG to 2,3 BPG.
- 2,3 BPG binds to the beta chains of HbA and decreases its affinity for oxygen
- (shifts Hb/O2 curve to the R. Normal R shifts allow for O2 to be unloaded in tissues)
- an abnormal increase in RBC 2,3-BPG might shift the curve far enough to the R that HbA is not fully saturated in the lungs
- 2,3-BPG doesn't bind well to HbF because HbF doesn't have a beta subunit.
*Summary:
- 2,3-BPG decreases O2 affinity for Hb
- 2,3-BPG increases O2 unloading
- 2,3-BPG regulates how RBC carries O2

- HbF has a higher affinity for O2 than maternal HbA
- this allows transplacental passage of O2 from mother to fetus