Carbohydrate Metabolism Flashcards Preview

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Flashcards in Carbohydrate Metabolism Deck (45):
1

Can glucose cross cell membrane, why?

No, it is too large and polar to be able to cross. It therefore requires the use of GLUTs (glucose transporters) that are located on the cell membrane or special case in a GLUT vesicle.

2

GLUT1

ubiquitous (found everywhere), high affinity (low Km) for glucose, used mainly in RBCs and brain. Facilitated diffusion.

3

GLUT2

Low affinity (high Km) for glucose, main transporter in liver. In a fed state, there is a surplus of glucose going through the liver, therefore the affinity of GLUT2 doesn't have to be that high. Facilitated diffusion

4

GLUT3

Main glucose transport in neurons, also has a high affinity (low Km) for glucose. Facilitated diffusion

5

GLUT4

Glucose transporter present in skeletal muscle, heart and adipose tissue. This transporter is INSULIN DEPENDENT/regulated by insulin. Facilitated diffusion. Found in vesicles within cytosol of cell. When insulin binds to a surface receptor, it signals the GLUT4 vesicle to fuse with the plasma membrane, now creating channels available for glucose uptake.

Fed state > Insulin released > GLUT4 binds to membrane > glucose uptake.

6

GLUT5

Transports glucose and fructose through the cell membranes. Facilitated diffusion

7

Glycolysis products

anaerobically: 2 pyruvate, 2 NADH, 2 ATP >> if continue 2 pyruvate are reduced to 2 lactate (muscle cells during exercise or red blood cells).
aerobically: pyruvate can be completely oxidized, or intermediates can go to other pathways.

8

three phases of glycolysis

1) investment: includes first three enzyme catalyzed reactions in glycolysis, uses 2 ATP.
2) Splitting: in two rxns the split of 1 6C molecule to 2 3C
3) Payoff: 4 ATP produced, 2 NADP produced.

9

What step of glycolysis traps glucose inside the cell

The first rxn in glycolysis phosphorylates glucose to G6P, which "traps" it inside the cell. All cells use HEXOKINASE to catalyze this rxn. The liver and pancreatic beta cells use GLUCOKINASE to catalyze this phosphorylation. This is a regulatory step

10

First regulatory step of glycolysis and what regulates it

The first regulatory step of glycolysis is the first rxn in glycolysis. Hexokinase or glucokinase use 1 ATP to phosphorylate glucose to G6P. G6P inhibit this step (feedback inhibition), Glucagon inhibits (excess glucose, stop making energy), Fructose 6-P inhibits, Glucose fructose 1-P and Insulin (fed state, make energy from food) activate this pathway. Hexokinase has high affinity for glucose, glucokinase has low affinity > mostly used after eating when glucose levels are elevated so affinity doesn't have to be very high

11

Isozymes

Enzymes with different structures, but the same function.

12

Rate limiting step of glycolysis, the enzyme of this step and regulators

The third rxn phosphorylates F6P to F1,6BP through the enzyme PHOSPHOFRUCTOKINASE-1. PFK-1 is positively regulated (continue through glycolysis) via AMP (more ATP needs to be generated -- hungry) and F2,6BP (product of side/parallel rxn) and high insulin/low glucagon (fed state). PFK is negatively regulated (slow/stop glycolysis) via ATP (have enough energy) or citrate (intermediate of TCA cycle).

13

glycolysis step that produces NADH

the 6th rxn of glycolysis converts G3P to 1,3BPG by using glyceralaldehyde 3-P dehydrogenase to reduce NAD+ to NADH (makes 2 NADH since theres 2 G3P).

14

Last regulatory step of glycolysis, enzyme and how it is regulated

The last rxn in glycolysis converts phosphoenolpyruvate (PEP) to pyruvate via PYRUVATE KINASE. Insulin and Fructose-1,6BP positively regulate PK (increase activity, has glucose, wants to make energy). Glucagon, ATP and ALANINE negatively regulate PK (has enough energy stored, slow glycolysis and PEP enters gluconeogenesis).

15

Hexokinase/glucokinase: compare

hexo: located everywhere, low Km, high affinity, low Vmax, glucose and other intermediates can be substrate, inhibited by G6P. glucokinase: located in liver and pancreatic beta, high Km, low affinity, high Vmax, glucose in the only substrate, not inhibited by G6P (but by glucagon)

16

Fed state ??????

and opposite is hungry (glucagon)

high insulin, stimulates protein phosphatase which dephosphorylates PK making it active allowing it to phosphorylate PEP to pyruvate.

17

G6P use in pathways other than glycolysis

Pentose phosphate pathway >> makes ribose for DNA/RNA and NADPH for those pathways, eventually used in galactose metabolism, glycogen synthesis

18

Pyruvate use in pathways other than glycolysis

transformed into oxaloacetate which is used in gluconeogenesis

converted to alanine for gluconeogenesis or protein synthesis

oxidized to acetly CoA and CO2 in TCA

reduced to lactate >> Cori cycle

19

glycolytic enzyme disorders often result in...

ineffective glycolysis = hemolytic anemia

20

Causes of type 2 diabetes

enzyme mutations, unable to convert proinsulin to insulin, defective insulin receptor, pancreatitis, pancreatic carcinoma

21

Tarui Disease

GSD VII: PFK-1 deficient > exercise induced muscle cramps/weakness, hemolytic anemia, jaundice,

22

Gluconeogenesis

creates glucose from carbohydrates (pyruvate) in liver, kidney and SI when blood glucose levels are low and glycogen stores are depleted. Not direct reversal of glycolysis. Uses lactate, AA and glycerol as precursors. Bypasses irreversible steps of glycolysis using different enzymes.

Would chose to breakdown 1) glycogen stores/lactate/other carbs(galactose/fructose) 2) fat/glycerol 3) proteins/alanine

23

glycolysis vs gluconeogenesis

gluconeogenesis uses: pyruvate carboxylase (PC), phosphoenolpyruvate carboxylkinase (PEPCK), F1,6BPhatase, G6Phatase

24

PC enzyme gluconeogenesis

converts pyruvate to oxaloacetate so it can pass from inner mitochondrial space to cytosol. it is found on mito membrane. OAA is converted to malate in mito, malate transferred through the membrane via malate shuttle and reoxidized to OAA in cytosol. Pyruvate carboxylase uses biotin cofactor.

25

Rate determining step of gluconeogenesis

converting F1,6BP to fructose 6P via FRUCTOSE 1,6-BISPHOSPHATASE. this enzyme is activated by cortisol and citrate (TCA intermediate). Inhibited by AMP and F26BP

26

Glucose 6-phosphatase location and function

Located on lumen of ER, the G6Ptase converts G6P to glucose. G6P transported into ER and converted to glucose which is then transported into cytosol by GLUT 7

27

GLUT 7

on ER lumen and transports glucose from lumen into cytosol in final step of gluconeogenesis

28

Cori Cycle

in RBC and exercising muscle: moves lactate (produced by anaerobic glycolysis) into blood supply and then into liver for gluconeogenesis

29

Fructose-1,6-bisphosphatase deficiency and its results on gluconeogenesis

similar to Tarui, but for gluconeogenesis. presents infancy. hypoglycemia, lactic acidosis, ketosis, apnea

30

Von Gierke disease

GSD1a: glucose 6 phosphatase deficiency = can't take final phosphate of of G6P in gluconeogenesis so unable to produce free glucose. Hepatomegaly, lyperlipidemia,

31

GLUT 2 mutation

Fanconi-Bickel syndrome: can't uptake glucose, fructose or galactose. Autosomal recessive disorder leads to hepatomegaly, resistant rickets. Treated with a special diet.

32

Polyol Pathway

converts glucose to fructose via sorbitol intermediate. Cells without sorbitol dehydrogenase will accumulate sorbitol >> water influx >> swelling >> cataracts

33

Fructose metabolism

Doesn't rely on PFK-1 so the rate determining step of glycolysis is skipped >> faster metabolism >> easier converted into fat >> less healthy

34

Galactose metabolism

GALT (glucose 1P uridyltransferase) is the rate limiting step

35

GALT deficiency

glucose 1P uridyltransferase: galactitol accumulates >> liver failure/sepsis/bleding

36

PPP (pentose phosphate pathway)

the purpose is to create ribose used in DNR/RNA and NADPH used for biosynthesis. occurs in cytosol. Has an oxidative and nonoxidative phase.

Oxidative: G6P dehydrogenase (RATE LIMITING STEP) G6PD deficiency results in hemolytic anemia

non-oxidative: ribose is creates from ribulose and an isomerase. other glycolysis/gluconeogenesis metabolites are also created. Reversible reactions.

37

What is glycogen

large glucose storage molecules when excess glucose in in body. has a 1,4 glycosidic bonds between linear sections and a1,6 glycosidic bonds at branch points. connected to a protein primer/glycogenin at the reducing end. non-reducing ends are added glucose at C4-OH

38

where is glycogen stored

in the liver and muscle as granules (enzymes necessary + glycogen)

liver glycogen regulates BLOOD glucose

Muscle glycogen provides fuel for physical activity

39

glycogenesis

process of making and extending glycogen molecules from glucose units.

glucose still trapped in cell by phosphorylating to G6P > G1P > UDP-glucose

40

rate determining step of glycogenesis

GLYCOGEN SYNTHASE transfers glucose from UDP-glucose to the non-reducing (4C-OH of glucose) by forming a1,4 glycosidic bond

41

How does glycogen branch

GLYCOSYL 4:6 TRANSFERASE breaks linear 11 glucose chain and attaches a 7 glucose chain to the 4th glucose away from previous branch or core protein.

42

glycogenolysis

Rate limiting step is GLYCOGEN PHOSPHORYLASE which cleaves glucose residues until within 4 glucoses from branch point.

43

Debranching glycogen

the Debranching enzyme releases the glucoses of the branch until the last one until glucosidase cuts the final glucose off the branch leaving a new linear glycogen chain to be degraded by GLYCOGEN PHOSPHORYLASE

44

regulation of Glycogen Synthase

dephosphorylated is the active form and phosphorylated is the inactive form

45

regulation of Glycogen Phosphorylase

phosphorylated is the active form and dephosphorylated is the inactive form