CHEM 1050 Flashcards

Flashcards for metabolism and hormonal regulation, glycolysis and the TCA cycle, glycogenolysis and GNG, PPP and Monosaccharide Metabolism

Endocrine

Cells secrete the hormone into the blood, exerting action on target cells that can be very far away, usually at high concentrations.

Paracrine

Substance is secreted from cells that are not normally thought of as endocrine cells and perform actions on nearby cells.

Autocrine

Act on the cell from which it is secreted or on nearby cells that are the same type of cell as the secreting cell.

Cellular signaling

Begins with the release of a chemical messenger

Intracellular receptors

Bind hydrophobic chemical messengers and usually elicit a transcriptional response.

Membrane receptors

Bind hydrophilic chemical messengers and usually directly change enzyme activity thru protein-protein interactions.

Cortisol

Released from the adrenal cortex and diffuses into the bloodstream, binding to serum albumin and steroid hormone binding globulin.

Hormone response element (HRE)

A portion of the DNA that the hormone-receptor complex binds to, resulting in either an increase or decrease in gene transcription.

G-Protein-Coupled Receptor cascade

Hormone binds to an extracellular domain of a 7-helix receptor, causing a conformational change in the receptor.

Adenylyl cyclase

Catalyzes synthesis of cAMP.

Phosphodiesterase

Degrades cAMP and terminates the signal

Gαs

Increases cAMP

Gαi

Decreases cAMP

Gαq

Increases phospholipase C activity

Insulin signaling

Amplify signals through kinase cascades.

Receptor Tyrosine Kinase

Receptors are in the cell membrane and dimerize upon ligand binding.

Autophosphorylation

Occurs on the inner side of the membrane upon binding of hormone to the receptor.

Insulin Receptor Substrate (IRS)

Binds other proteins to amplify the signal when phosphorylated

Phosphatidylinositide metabolism

Provides a connection between the hormone receptor and intracellular calcium

Phospholipase C

Cleavage of PIP2 yields inositol-1,4,5-trisphosphate (IP3) and diacylglycerol (DG)

Inositol-1,4,5-trisphosphate (IP3)

Enhances Ca2+ release from the endoplasmic reticulum

Diacylglycerol (DG)

Activates Protein kinase C

Kinases

Catalyze sequential transfer Pi from ATP to hydroxyl groups at positions 5 & 4 of the inositol ring of phosphatidylinositol, to yield phosphatidylinositol-4,5-bisphosphate (PIP2)

FED state

Insulin levels are elevated, glucagon, cortisol, and epinephrine are low

Fuel used by the liver in the FED state

Dietary glucose

Fuel used by the skeletal muscle in the FED state

Dietary glucose (insulin-sensitive)

Fuel used by the red blood cells in the FED state

Dietary glucose

Fuel used by the brain in the FED state

Dietary glucose

Fuel used by the adipose tissue in the FED state

Dietary glucose (insulin-sensitive)

FASTED state

Insulin levels are low, glucagon, cortisol, and epinephrine are elevated

Fuel used by the liver in the FASTED state

Free fatty acids

Fuel used by the skeletal muscle in the FASTED state

Free fatty acids

Fuel used by the red blood cells in the FASTED state

Glucose

Fuel used by the brain in the FASTED state

Glucose

Fuel used by the adipose tissue in the FASTED state

Fatty acids

Pathways in the liver enhanced by insulin

Glycolysis, TCA, Glycogen synthesis, Fatty acid synthesis, Protein synthesis

Pathways in the liver enhanced by glucagon

Lipolysis, β-oxidation of fatty acids

Pathways in the liver enhanced by epinephrine

Glycogenolysis (via alpha-agonist pathway), Lipolysis, β-oxidation of fatty acids

Pathways in the liver enhanced by cortisol

Glycogenolysis, Gluconeogenesis

Pathways in the skeletal muscle enhanced by insulin

Glucose uptake through GLUT4, Protein synthesis, Glygogen synthesis

Pathways in the skeletal muscle enhanced by epinephrine

Glycogenolysis

Pathways in the skeletal muscle enhanced by cortisol

Promotes protein catabolism to provide amino acids for gluconeogenesis occurring in the liver

Pathways in the Adipose enhanced by insulin

Triacylglycerol synthesis, Glucose uptake through GLUT4

Pathways in the Adipose enhanced by epinephrine

Lipolysis

Glycolysis

Cytosolic pathway where glucose is broken down.

Energy-requiring phase of glycolysis

Requires 2 ATP, rearranges the starting molecule of glucose, and attaches two phosphate groups.

Energy-releasing phase of glycolysis

Produces 4 ATP and 2 NADH by converting each three-carbon sugar into pyruvate.

Aerobic pathway

Glucose is oxidized to pyruvate and oxidation continues in the mitochondria to generate acetyl-CoA.

Anaerobic pathway

Glucose is oxidized to lactate, occurring in the absence of oxygen or in cells lacking mitochondria.

Isozymes

Catalyze the same enzymatic reaction but differ in amino acid sequence.

Hexokinase

Has a low Km for glucose and is found in tissues other than the liver; rapidly saturated.

Glucokinase

Has a high Km for glucose and is found in the liver or pancreas; not rapidly saturated.

Phosphofructokinase-2 (PFK2)

Catalyzes the conversion of Fructose 6-phosphate to Fructose 2,6-bisphosphate and is not considered part of glycolysis but is a shunt of the pathway

Fructose 2,6-bisphosphate

Enhances the activity of PFK1 (allosteric activator)

Fructose 1,6-bisphosphate

A FEEDFORWARD activator of Pyruvate kinase

Pyruvate Kinase (PK)

Catalyzes the irreversible reaction of PEP to pyruvate

Pyruvate

Can either enter the TCA cycle through the pyruvate dehydrogenase complex, be converted to lactate under anaerobic conditions, or be transaminated to alanine.

GKRP

Regulator of Glucokinase (liver)

Hexokinase

Inhibited by Glucose 6P

PFK-1

Activated by Fructose 2,6-BP and AMP, inhibited by Citrate

Pyruvate kinase

Activated by Fructose 1,6-BP, inhibited by ATP and alanine

Pyruvate dehydrogenase complex PDC

Activated by Pyruvate and NAD+, inhibited by Acetyl-CoA, NADH, and ATP

Pyruvate dehydrogenase complex regulation

-Acetyl CoA, -NADH -phosphorylation by the pyruvate dehydrogenase kinase

Pyruvate dehydrogenase kinase regulation

Phosphorylation by pyruvate dehydrogenase kinase inactivates the complex

Aconitase

Inhibited by fluoroacetate

Isocitrate dehydrogenase regulation

-NADH +ADP +Ca2+. Physiologically unidirectional step in the TCA

α-ketoglutarate dehydrogenase regulation

-NADH +Ca2+. Physiologically unidirectional step in the TCA. Inhibited by arsenite

Succinate thiokinase

Substrate level phosphorylation

Succinate dehydrogenase

Only enzyme of TCA embedded in the mitochondrial membrane (it is also Complex II in the ETC and will oxidize FADH2)

Malate dehydrogenase

Oxaloacetate also produced from aspartic acid. Oxaloacetate production is dependent on the ratio of NADH/NAD+

Fatty acid synthesis connection to the TCA

Citrate is shuttled out of the TCA and is cleaved by citrate lyase to generate: acetyl-CoA and oxaloacetate (OAA).

Anaplerotic reactions

Reactions that transfer net carbon into the TCA cycle

Anaplerotic reaction

Carboxylation of pyruvate → oxaloacetate (by pyruvate carboxylates)

Transamination reactions (specifics of this reaction are covered in Unit 4)

Glutamate → alpha-ketoglutarate, Alanine → pyruvate, Aspartate → oxaloacetate

Glycerophosphate shuttle (Glycerol 3-phosphate shuttle)

Moves reducing equivalents of NADH from the cytosol to an FAD in the mitochondrion

FAD is a required cofactor

Glycerol 3-phosphate dehydrogenase

Malate-Aspartate shuttle

Oxaloacetate is REDUCED to malate by cytosolic malate dehydrogenase

TRANSAMINATION REACTION with glutamate generates

Alpha-ketoglutarate and aspartate

Glycogen

Stored primarily in the liver and skeletal muscle.

Phosphoglucomutase

Glucose 6-P is isomerized → Glucose 1-P

UDPGlc pyrophosphorylase

Glucose 1-P + UTP → UDPGlc

Glycogen synthase

Adds UDPGlc →terminal end of glycogen (1→4 linkage)

Glycogen phosphorylase

Releases glucose 1-P from glycogen

Glucose 6-Phosphatase

Glucose 6-P → Free Glucose

Enzyme is required to de-phosphorylate glucose to be released from the liver

Key difference in liver vs. muscle glycogenolysis

Glucagon activation of GPCR

Activation of Adenylate cyclase → increases cAMP

cAMP activates Protein kinase A (PKA)

cAMP activates Protein kinase A (PKA) →phosphorylates phosphorylase kinase → phosphorylated phosphorylase kinase → phosphorylates glycogen phosphorylase→ glycogen degradation

cAMP activates PKA

cAMP activates PKA → phosphorylates glycogen synthase → inactivates

Epinephrine binds α-adrenergic

Cleavage of PIP → IP3 and DAG

IP3

Stimulates Ca2+ release from ER

DAG

Activates protein kinase C (PKC)

Skeletal muscle

Muscle is NOT impacted by GLUCAGON

↑, ↓

Increases activity, decreases activity

Gluconeogenesis

Predominantly occurs in the liver

Gluconeogenesis substrates

Substrates: Lactate, Glycerol, Amino acids

NOT a substrate for Gluconeogenesis

FATTY ACIDS or KETOGENIC amino acids

Pyruvate carboxylase (PC)

Carboxylates pyruvate to OAA

Phosphoenol pyruvate carboxykinase (PEPCK)

Converts cytosolic OAA → phosphoenol pyruvate

Fructose 1,6-bisphosphatase (FBP-1)

Converts fructose 1,6-bisphosphate to fructose 6-phosphate

Glucose 6-phosphatase

Dephosphorylates glucose 6-phosphate to free glucose that can be released from the liver