M2C Unit 2 Lesson 8 and 9

What is Gluconeogenesis?

synthesis of glucose from noncarbohydrate precursors

Gluconeogenic Substrates

• Lactate • Glycerol • Amino acids

biotin is not carboxylated unless __ is bound to the enzyme.

acetyl-CoA

ABC Carboxylase

A for ATP, B for Biotin and C is carbon dioxide

Bicarbonate + Pyruvate with the enxyme pyruvate carboxylase yields?

Oxaloacetate

Bicarbonate + Pyruvate → Oxaloacetate with what enzyme?

pyruvate carboxylase

Bicarbonate + Pyruvate → Oxaloacetate requires what cofactor?

biotin

What is Phosphoenolpyruvate carboxykinase?

PEPCK

Oxaloacetate → phosphoenolpyruvate (PEP) enzyme

Phosphoenolpyruvate carboxykinase (PEPCK)

Most enzymes of gluconeogenesis are?

cytossolic

Glucose 6-phosphatase location

ER

Pyruvate carboxylase location

mitochondria

PEPCK location

cytosol and/or mitochondria

F1,6BPase is allosterically inhibited by?

AMP and fructose 2,6-bisphosphate

Precursors for Gluconeogenesis

• lactate

• most AA

• glycerol

What is The Cori Cycle?

The interaction of glycolysis and gluconeogenesis

What is teh The glucose-alanine cycle?

(1) Transamination of pyruvate yields alanine which travels to the liver

(2) Transamination of alanine in the liver yields pyruvate for gluconeogenesis

(3) Glucose is released to the bloodstream

__ of the 20 common amino acids are able to donate their carbon skeletons to gluconeogenesis

18

Which two AA are unable to donate their carbon skeletons to gluconeogenesis?

leucine and lysine (breakdown is limited to acetyl-CoA)

Glycerol enters glycolysis by converting to?

DHAP

What is Propionate converted to?

acetyl-CoA

How is Propionate is converted to succinyl CoA?

propionyl-CoA carboxylase then methylmalonyl-CoA epimerase and finally the vitamin B12 requiring enzyme, methylmalonyl-CoA mutase

Stoichiometry of Gluconeogenesis

2 Pyruvate + 2 NADH + 4 ATP + 2 GTP + 6 H2O → Glucose + 2 NAD+ + 4 ADP + 2 GDP + 6 Pi + 2 H+

Gluconeogenesis activators

citrate and acetyl-CoA

Gluconeogenesis inhibitors

F2,6-BP, AMP, and ADP

glucagon which is high in starvation activates what enzyme?

PEPCK and fructose 1,6-bisphosphotase

What is another name for the Pentose Phosphate Pathway?

hexose monophosphate (HMP) shunt

How can Glucose enter PPP?

after converting to Glucose 6-phosphate

PPP products

NADPH and Ribose 5-phosphate (NO ATP generated)

Which tissues is PPP active in?

tissues that synthesize fatty acids or steroids (liver, mammary and adrenal glands, and adipose tissue) and RBC to produce NADPDH to maintain reduced iron

PPP is split into what two stages?

Oxidative and Non-oxidative

Which stage of PPP is irreversible?

Oxidative stage

PPP requires what cofactor and when?

TPP (Thiamin/B1) with the enzyme Transketolase

End product of Oxadative stage of PPP

Ribose 5-Phosphate

The activity of the PPP is high/low in tumor cells, which are constantly replicating their DNA as tumors grow.

high

What is ribose 5-phosphate used for?

in nucleic acid formation

What is NADPH?

reduced form of nicotinamide adenine dinucleotide phosphate (NADP+) and the second player in the PPP with its own unique roles.

Non-oxidative stage of PPP has what two major enzymes?

transketolase and transaldolase

NADPH is a product of what stage of PPP?

Oxidative Stage

What Is the Role of NADPH in Cholesterol Synthesis?

NADPH is essential in the synthesis of cholesterol,

• Cholesterol precursor to

  • corticosteroids,

  • sex hormones,

  • bile acids,

  • vitamin D.

What is HMG-CoA reductase?

(the rate-limiting enzyme and also the site of action of statins) is involved in the conversion of HMG-CoA to mevalonate. in cholesterol synthesis

HMG-CoA reductase requires which cofactor?

NADPH

Role of NADPH in the Cytochrome P450 Monooxygenase System

The cytochrome P450 (CYP) monooxygenase consists of a family of CYP enzymes that contain heme.

• The CYP monooxygenase system catalyzes the reaction between a substrate and oxygen (O2).

How Does NADPH Handle Oxidative Stress?

NADPH helps neutrophils destroy microbes that invade our body in the respiratory burst system.

• This process that requires NADPH, powerful oxygen metabolites, superoxide and hydrogen peroxide, help kill microbes

Role of Glutathione Peroxidase?

compound that helps cells detoxify a ROS by converting it to a harmless metabolite of water

G6PD deficiency aggrivators

oxidative stressors such as fava beans, sulfa drugs, and infections

G6PD deficiency manifestations

hemolytic anemia leading to unconjugated hyperbilirubinemia

What is Chronic granulomatous disease?

deficiency of NADPH oxidase, leading to a decrease in production of ROS and absent respiratory burst

• leads to an increased susceptibility to catalase-positive organisms like Pseudomonas, Listeria, Aspergillus, Candida, Staphylococcus aureus, Escherichia coli, and Serratia

Final products of PPP (non-oxidative/final stage)

Glyceraldehyde 3-phosphate (GAP) and Fructose 6-phosphate (x2)