Lecture 32 Carbohydrate Metabolism and Regulation

The rate of glycolysis is typically controlled by the _______ concentration.

glucose

The rate of gluconeogenesis is typically controlled by the concentrations of _______ and other glucose precursors.

lactate

If both glycolysis and gluconeogenesis were highly active at the same time the result would be a ______ ______ consuming two ATP and two GTP per reaction cycle.

futile cycle

The production of ___ and ________ ______ for synthesis of other molecules regulate the rate of glycolysis (glucose to pyruvate).

ATP; building blocks

Glucose is used to make ribose in the _______ ________ _______

pentose phosphate pathway

__________ is the enzyme involved in the phosphorylation of glucose during the first step of glycolysis. (___________ in the liver)

Hexokinase; glucokinase

_______-_-_________ can be used for glycolysis, the pentose phosphate pathway to make nucleotides, glycogen synthesis, and other pathways such as sugar derivatives.

Glucose-6-phosphate

Glycolysis is an _________ process which makes 2 pyruvate, 2 ATP, and 2 NADH.

anaerobic

During stage _ of glycolysis, ATP must be coupled to reactions to drive them forward.

1

During stage _ of glycolysis, energy is generated in the form of ATP.

2

ATP is generated during glycolysis and the TCA cycle via _________-_____ _______________.

substrate-level phosphorylation

Oxidative phosphorylation occurs in the ____________

mitochondria

_________-_____ _______________ is the formation of ATP from a high phosphoryl transfer potential substrate.

Substrate-level phosphorylation

During the first few steps of glycolysis, glucose is activated by _______________ with ATP (__________ and ___-_ enzymes are involved in these steps)

phosphorylation; hexokinase; PFK-1

Phosphorylation of glucose and all subsequent intermediated ensures that they ______ __ ___ ____

remain in the cell

There are _ steps at which ATP is produced in glycolysis (___ and __ are the enzymes for these steps)

2; PGK; PK

Aerobic respiration involves both _________ and substrate-level phosphorylation.

oxidative

Anaerobic respiration only involves _________-_____ _______________.

substrate-level phosphorylation

Anaerobic glycolysis eventually forms _______ while aerobic respiration goes into the ___ _____.

lactate; TCA cycle

During anaerobic respiration, NADH must be reoxidized by ______ ____ ____________ as opposed to aerobic respiration where it can be reoxidized by the ETC via oxidative phosphorylation.

lactic acid fermentation

The only purpose of lactic acid fermentation is to regenerate ____ for glycolysis (production of 2 ATP via substrate-level phosphorylation).

NAD+

The enzyme _______ _____________ reduces NADH to NAD+ during lactic acid fermentation.

lactate dehydrogenase

Under aerobic conditions, electrons are shuttled into the mitochondria so ____ can be reduced for glycolysis.

NADH

NADH is transferred into the mitochondria via ________

shuttles

Glycolysis provides precursors for:

5 carbon sugars
Fatty acid biosynthesis (from pyruvate)
Amino acids (alanine, serine, glycine, cysteine)
Triacyl glycerol
2,3 bisphosphoglycerate for Hb function

Steps _, _, and __ in glycolysis are regulated and have a very negative delta G.

1, 3, and 10

___-_ is the enzyme involved in the third step of glycolysis.

PFK-1

__ is the enzyme involved in the last step of glycolysis.

PK (Pyruvate Kinase)

Hexokinase has a _____ Km than glucokinase which is found in the liver and pancreatic B cells.

lower (enzyme has higher affinity for substrate)

__________ is inhibited by its product (ATP) while ____________ keeps going in the presence of its product.

Hexokinase; glucokinase

The chief controlling enzyme of glycolysis is ___________________-_ because it regulates the first unique step of glycolysis.

phosphofructokinase-1 (PFK-1)

PFK-1 is allosterically inhibited by _______ and ___

citrate, ATP

PFK-1 is allosterically activated by ___, ___, and ________ _,_-___________

AMP; ADP; fructose 2,6-bisphosphate

Fructose-2,6-bisphosphate is a product of ___-_ which links glycolysis to ________ control (insulin).

PFK-1; hormonal

Fructose-2,6-biphosphate __________ glycolysis and ________ gluconeogenesis.

stimulates; inhibits

_______ activates PFK-2 by dephosphorylating it which increases production of F26BP which then stimulates glycolysis, causing breakdown of glucose in order to synthesize lipids after glycogen storage is full.

Insulin

________ ______ controls the outflow from the glycolysis pathway. It is the last irreversible step which yields ___ and ________.

Pyruvate kinase; ATP; pyruvate

Under conditions of low glucose, pyruvate kinase is phosphorylated which ___________ it.

inactivates

Under conditions of high glucose, pyruvate kinase is dephosphorylated which _________ it.

activates

Galactose is a _-_ epimer of glucose.

C-4

Mannose is a _-_ epimer of glucose.

C-2

Other ______ ______ enter into glycolysis and are broken down into pyruvate.

hexose sugars (galactose, mannose, fructose)

The _______ of gluconeogenesis are different than those used in glycolysis, because the reactions are taking place in reverse.

enzymes

_______-_-___________ is an enzyme of gluconeogenesis that is found in the ER.

Glucose-6-phosphatase

________ ___________ and _____ are enzymes used in gluconeogenesis which are found in the mitochondria.

Pyruvate carboxylase; PEPCK

Pyruvate can be converted to _______ and used in the cytosol for the synthesis of fatty acids.

citrate

Pyruvate can be converted to ____________ for gluconeogenesis.

oxaloacetate

___-_ is a hormonal enzyme which is regulated by insulin and glucagon.

PFK-2

The irreversible steps in glycolysis are the same as the irreversible (regulated) steps in _______________

gluconeogenesis

_______-_,_-______________ is an enzyme that catalyzes the dephosphorylation of fructose 1,6-bisphosphate in gluconeogenesis.

Fructose-1,6-bisphosphatase

F16BPase is inhibited by _____, ___, and ___.

F26BP; ADP; AMP

F16BPase is activated by _______

citrate

The process of gluconeogenesis is most common in the _____ because it absorbs glucose after all other organs.

liver

_______-_-___________ is an enzyme which performs the reverse reaction of hexokinase during gluconeogenesis.

Glucose-6-phosphatase

The precursor to pyruvate during glycolysis is ___________________.

phosphoenolpyruvate

Low blood glucose leads to an increase in glucagon, which leads to an increase in ____ which activates a cAMP dependent protein kinase A. This kinase ______________ transcription factors to induce expression of _____ (enzyme catalyzes oxaloacetate to phosphoenolpyruvate)

cAMP; phosphorylates; PEPCK

________ ___________ catalyzes the reaction of pyruvate to oxaloacetate in gluconeogenesis.

Pyruvate carboxylase

_____ catalyzes the reaction of oxaloacetate to phosphoenolpyruvate in gluconeogenesis.

PEPCK (phosphoenol-pyruvate carboxykinase)

______ ___ is an allosteric activator of pyruvate carboxylase.

Acetyl CoA

Any metabolite that can be converted to ________ or ____________ can be a glucose precursor. (ex. lactate, amino acids)

pyruvate; oxaloacetate

________ can enter into glycolysis or gluconeogenesis after being released from triglycerides.

Glycerol

During the ____ _____, lactate produced from glucose via glycolysis and lactic acid fermentation in the blood is converted back to glucose via gluconeogenesis in the liver.

Cori cycle

Red blood cells lack ____________ so they use _________ respiration which causes the production of _______ that has to be turned back into glucose by the liver.

mitochondria; anaerobic; lactate

__________ increases glucose availability between meals, usually via the breakdown of ________ and ____.

Catabolism; glycogen; fats

Glycogen is stores in the _____, ______, and _______.

liver; muscle; kidneys

____ have the highest amount of energy per molecule.

Fats

Glycogen releases _______-_-_________ which has to be converted to _______-_-_________ for further metabolism.

glucose-1-phosphate; glucose-6-phosphate

________ regulation of glycogen metabolism leads to the reversible phosphorylation of enzymes.

Hormonal

In order to synthesize glycogen, ___-_______ (activated) is added to the nonreducing end on glycogen.

UDP-glucose

All glucose cannot be stored in the form of glycogen because sugars are ___________ and too much water is needed for all glucose to be stored this way (swelling).

hydrophilic

Glycogen bonds are _____ _-_, with _____ _-_ branching every 8-14 residues.

alpha 1-4; alpha 1-6

________ _______ adds glucose to the non-reducing end of glycogen.

Glycogen synthase

Glycogen stores in the ______ can only be used within that cell, while stores in the _____ are sent out to other tissues.

muscle; liver

________ regulate the mobilization and synthesis of glycogen.

Hormones (insulin, glucagon, epinephrine)

_______-_-_________ is a positive regulator of glycogen synthesis. (cell needs to store glucose)

Glucose-6-phosphate

_______-_-_________ and ___ are negative regulators of glycogen phosphorylase which catalyzes glycogen buildup. (no need to break down glucose if there is a lot present)

Glucose-6-phosphate; ATP

_______ ________ is caused by a defective enzyme which causes a large increase in glycogen. Enzyme replacement therapy is used to treat this which is very expensive.

Pompe's disease

When glucose is metabolized to lactate in skeletal muscle, how is ATP generated?

Substrate-level-phosphorylation

How are glycolysis, ethanol fermentation and lactic acid fermentation related?

Can occur in the absence of oxygen

How is glucose kept inside the cell, against a concentration gradient?

By conversion to glucose-6-phosphate

What is the source of gluconeogenic precursor lactate?

Lactate comes from anaerobic glycolysis from muscle and red blood cells

Fructose 2,6-bisphosphate and AMP are both negative allosteric effectors of which enzyme?

F16BPase

Most gluconeogenic enzymes are found in the cytoplasm. Where is the enzyme glucose-6-phosphatase located?

ER