BIOCHEM EXAM 4: PPP

Aldehyde + Alcohol (reversible arrows)

Hemiacetal

Ketone + Alcohol (reversible arrows)

Hemiacetal

What is glucopyranose?

(6C) glucose in ring form

What is glucofuranose?

(5C) glucose in ring form

What are these arrows pointed to?

anomeric C atom

If monosaccharide rxns occur in an intramolecular fashion, the product

is a ring

What is the equilibrium aqueous mixture of glucose at standard glucose conditions?

33% - alpha anomer

66% - beta anomer

<1% - linear

Do hexokinase and most glycolytic enzymes care about aqueous mixture of glucose?

hexokinase and most glycolytic enzymes don’t care as long as it’s a monosaccharide, since interconversion is so fast

What monosaccharides are important to know for biochemistry?

Ribose, Deoxyribose, Glucose, Mannose, Galactose, Fructose

What branched sugar comes from cereals, tubers, breads?

starch/amylopectin

What enzyme acts on starch/amylopectin, and where is it expressed?

amylase; expressed in salivary glands, intestines (at least 4 glucose)

Starch/amylopectin (Amylase→)

Many glucose molecules

What disaccharide comes from germinated cereals?

maltose

What enzyme acts on maltose and sucrose, and where is it expressed?

sucrase; intestines

What disaccharide comes from table sugar, fruits?

sucrose

Maltose (Sucrase→)

2 glucose

Sucrose (Sucrase→)

1 Glucose + 1 Fructose

What disaccharide comes from mammalian milk?

Lactose

What enzyme acts on lactose, and where is it expressed?

lactase; infant intestines (retained in adulthood in some humans)

Lactose (Lactase→)

1 glucose + 1 galactose

What 2 saccharides cannot go straight to glycolysis?

Fructose + Galactose

Where does fructose metabolism mostly take place?

the liver

What is the Step 1 of fructose metabolism?

Fructokinase phosphorylates Fructose into F1P

What is Step 2 of fructose metabolism?

Aldolase B chops F1P into Glyceraldehyde and DHAP

What is Step 3 of fructose metabolism?

• TPI converts F1P into G3P

• Triokinase converts Glyceraldehyde into G3P

What step bypasses the PFK-1 valve?

Why do we now think excess dietary fructose is harmful?

What happens to the G3P made by fructose metabolism?

plugged into gluconeogenesis or glycolysis as needed

What is galactose metabolism also referred to as?

Leloir’s Pathway

What is Step 1 of galactose metabolism?

Galactokinase turns a-D-galactose into Galactose-1-Phosphate

What step of Leloir’s Pathway uses ATP?

Step 1 dephosphosphorylates it into ADP

What is Step 2 of galactose metabolism?

GALT transfers a UDP to Galactose-1-Phosphate to create UDP-Galactose

UDP Galactose is in equilibrium w/…

UDP-Glucose

What is Step 3 of galactose metabolism?

UDP-Galactose Epimerase rearranges UDP-Galactose into G6P

What type of Diabetes Mellitus involves no insulin (congenital, beta cells in pancreas are killed by autoimmune response?

Diabetes Mellitus Type 1

What type of Diabetes Mellitus involves insulin resistance/insensitivity (age, BMI, genetics)?

Diabetes Mellitus Type 2

What is hyperglycemia?

consistently elevated blood sugar

In either forms of diabetes: high [glucose] in cell does what?

saturates hexokinase

When hexokinase is saturated, glucose will enter the…

unintended “polyol pathway”

Step 1 of “Polyol Pathway”

Using NADPH, Aldose reductase reduces Glucose to Sorbitol

Glucose-6-P-dehydrogenase is highly specific for…

NADP+

What does the phosphate in NADP+ do?

tags the activated carrier as reserved for anabolic rxns

Step 2 of “Polyol Pathway”

Using NAD+, Sorbitol dehydrogenase turns Sorbitol into Fructose

What is the original function of Aldose reductase?

detoxification

Why is Aldose reductase not meant to bind glucose?

bc it has a high K_m

What enzyme gets saturated easily?

Sorbitol dehydrogenase

What does a high build-up of sorbitol inside cells do?

it changes the osmolarity (causes osmotic stress)

What cell shave a high baseline glucose uptake?

LuRKS (Lens, Retina, Kidneys, Schwann cells)

What are Schwann cells?

glial cells of peripheral nervous system

What is diabetic retinopathy?

damage to retinal microvasculature →visual impairment

What is diabetic neuropathy?

peripheral nerve dysfunction causing pain, tingling, or abnormal sensation

What is the Pentose Phosphate Pathway (PPP) also called?

Hexose Monophospahte (HMP) Shunt

What EC do cells need for reductive anabolism?

NADPH

PPP can be used to make…

NADPH and nucleotides

What sugar does PPP make?

ribose-5-phosphate

What process is ribose-5-phosphate essential for?

nucleotide synthesis

Which 3 places does PPP mainly occur?

1. liver

2. adipocytes

3. erythrocytes (RBCs)

Where do PPP rxns take place cellularly?

the cytosol

PPP is divided into

OXIDATIVE (linear) and NON-OXIDATIVE (non-linear) pathways

Step 1 of PPP

Using NADP+, Glucose-6-P-dehydrogenase oxidizes G6P into 6-Phosphogluconolactone

What type of rxn is Step 1 of PPP?

redox

What step of PPP is the “committed” step; and why?

Step 1; 2 + 3 are highly thermo. favored

Feedback inhibition is done by NADPH in which step of PPP?

Step 1

When is Step 1 of PPP activated?

When E is high (ATP/AMP high) and NADPH levels are low

What is Step 2 of PPP?

Gluconolactonase hydrolysizes 6P-Gluconolactone → 6P-Gluconate using H2O

In Step 2 of PPP, hydrolysis is very favored, nonetheless…

the enzyme (gluconolactonase) speeds it up even more

What is Step 3 of PPP?

Using NADP+, 6-Phosphogluconate dehydrogenase reduces 6P-Gluconate → 3-Keto-6P-Gluconate → Ribulose-5-P

What type of rxn is Step 3 of PPP?

Redox

What is 3-Keto-6P-Gluconate?

an unstable intermediate of Step 3 of PPP

What is Step 4 of PPP?

Phosphopentose Isomerase rearranges Ribulose-5-P (ketose) → Ribose-5-P (aldose)

What type of rxn is Step 4 of PPP?

isomerization

Which Step of PPP produces NADPH, one of the key reasons for the pathway?

Step 3

What is the Non-Oxidative Phase of PPP?

a set of fully reversible C rearrangements

Ribose and ribulose can become…

Sedoheptulose and G3P (which can reenter glycolysis)

Why should the cell further react Sedoheptulose to yield more G3P and F6P?

bc cells need NADPH more than ribose-5-phosphate so

What enzyme is needed for making G3P from 5-C molecules?

Transketolase

R5P + Xylulose-5-P (? → ) G3P + Sedoheptulose-7-P

? = Transketolase

Erythrose-4-P (? → ) G3P + F6P

? = Transketolase

What two pathways does transketolase connect?

PPP → Glycolysis (feeding excess sugar phosphates into it)

What vitamin does transketolase require for function?

Thiamine (Vitamin B1)

In contrats to glycolysis, G-6-P dehydrogenase is activated when..

ATP/AMP are high and NADPH levels are low

What are the 4 Modes of the PPP?

1. Non-oxidative pathway runs in reverse

2. Only oxidative steps run

3. G3P fed back into gluconeogenesis

4. G3P sent into glycolysis

Which Mode is run when you only need Ribose?

Mode 1

What happens in Mode 1?

Non-oxidative pathway runs in reverse

Mode 1 can also just do a…

conformation change

Which Mode is run when you need both NADP and Ribose?

Mode 2

What happens in Mode 2?

Run only Oxidizing steps

What type of cell is likely to run Mode 2?

Muscle cell

What Mode is run when you only need NADPH?

Mode 3

What happens in Mode 3?

Run oxidative steps → Convert R5P into G3P → G3P is fed back into gluconeogenesis

Mode 2 is mostly used by cells wanting to do…

Nucleotide Synthesis

What type of cell is most likely to run Mode 3?

liver cells

What Mode is run when both NADPH and ATP are needed?

Mode 4

What happens in Mode 4?

Run Oxidative steps → R5P → G3P → G3P sent into glycolysis

What Mode is very common in erythrocytes (RBCs)?

Mode 4

Which Modes run oxidizing pathway?

2, 3, 4

Ribose-5-P (the product of Step 4) spontaneously…

forms ring