BC 31 Hexose Monophosphate Shunt

Question 1

Hexose Monophosphate Pathway
WHY
WHERE
WHEN

Answer 1

Generates NADPH and %C sugars for nucleic acid production

• most active during absorbtive phase of DNA rep
• in CYTOSOL
• One ox branch, two non ox

Question 2

Oxidative Branch of HMP

Reaction and Purpose

Answer 2

G6P and NADP–> Ribonse 5P and NADPH
-used G6PD (RATE LIMITING)

regulation:
+G6P
+NADP
-NADPH

PURPOSE :

1. FA synthesis in liver adipose and lactating mam gland
2. steroid synthesis in testes ovaries and plac and ad cortex
3. glucathione reduction in erythrocytes

R5P for nucleotide synthesis

Question 3

Non Ox Forward HMP

Answer 3

Ribose 5P –>Fructose 6 Phosphate and glyceraldehyde 3 phosphate

• uses Transketolase and TPP (coenzyme)
• –non regulated except lack of TPP

Reason: when we don’t need R5P this creates glycolytic intermediates for breakdown
-provides mechanism for metabolic use of 5 carbon sugars derived from carb breakdown

Question 4

Non Ox Reverse

Answer 4

F6P and Glyceraldehyde 3 P –> R5P
-transketolase and TPP

when bodies need for R5P increases and neeed for NADPH lowers. Remove glycolytic intermediates to 5C sugars

Question 5

high IG ratio on HMP

Answer 5

increase G6P for either HMP ox or glycolysis

Question 6

decrease in thiamine

Answer 6

INHIBIT:

• both non ox paths
• pyruvate dehydrogenase
• alpha ketogluterate DHC

Question 7

Cytosolic Citrate effects

Answer 7

inhibits PFK 1 (RL in Glycolysis)

• accumulation of G6P
• Ox branch of HMP shunt producing NADPH

-NADH for FA synth, glycolysis,

Question 8

Significance of NADPH

Answer 8

with mitochondria

• liver and muscle
• NADPH from (HMP OX and MALLIC enzyme)

without mitochondria

• RMC and Cornea/lens
• ox branch of HMP shunt is THE ONLY PATH

Question 9

Draw map of HMP shunt

Answer 9

check in notes

Question 10

H2O2 reduction with NADPH

Answer 10

Indirect

• Reactive oxidation species (ROS) is a byproduct of aerobic metabolism, drugs, toxins
• H2O2 accepts e-from reduced glutathione (G-SH)(natural antiox) and makes H2O

-goes to G-S-S-G - NAPDH donates e- to go back to G-SH

Glutathione is a tripeptide, requires atp for synthesis

Question 11

Fructose Metabolism
dietary source
entry into cel mechanism
two steps in metabolism

Answer 11

SUCROSE: fructose and glucose
-honey and fruit, free fructose

ENTRY into cells NOT insulin dependant
-also poor elicitor of insulin secretion (high glycemic index)

STEP 1 sugar trap

• phosphorylation of fructose by fructokinase
• in liner and kidneys/smooth intestine
• F1P trapped in cell

STEP 2 F1P–> DHAP and D glyceraldehyde BY aldolase
-D glyceraldehyde converted to Glyceraldehyde 3 P and both can enter glycolysis in fed state

OR metabolized by gluconeogenesis in fast or lipogensis

IMPORTANT: rate of fructose metabolism uncontrollable bc enters BELOW RL PFK1
-excessive acCOA leads to increased FA synthesis

Question 12

Fructokinase Deficiency

Answer 12

benign fructose accumulation

cannot trap in cells…leaks out…essential fructoseuria

Question 13

Dietary Galactose metabolism

Answer 13

epimer of glucose: less sweet

1. phosphorylation of Gal by falactokinase to G1P (trapped)
2. G1P –> UDP galactose and Glucose 1_
   -Gal–1-P uridyltransferase
3. UDP gal as C source for glycolysis via UDP hexose 4 epimerase
   Glucose 1P used in gluconeogenesis OR used again to add UDP to another Gal 1P again

confusion here

Question 14

Aldose reductase

Answer 14

high Km for galactose, no physiological importance until galactose is high
alsdose reductase convert galactose to galactitol
-sugar alcohol

in liver: broken down
other tissues: accumulates brings in H2O

Question 15

Galactokinase Deficiency:

Answer 15

accumulation of galactose in blood and urine
-shunted to aldose reductase–galactitol created and osmotically active, damage and precipitation of proteins (cataracts)