Liver Metabolism Fed State I

Front 1

Location of glycolysis

Back 1

cytosolic pathway, so in the cytosol (the only source of ATP from the cytosol)

Front 2

Aerobic glycolysis costs and yields

Back 2

2 ATP + 2 NAD+

yields

2 pyruvate + 4 ATP (2 net ATP) + 2 NADH

Front 3

Anaerobic glycolysis costs and yields

Back 3

2 ATP + 2 NAD+ + 2 NADH

yields

2 lactate + 4 ATP (2 net ATP)

no NADH, but NAD+ is regenerated

Front 4

Glucose 6 phosphate (G-6-P) can be used to run concurrently through which three pathways?

Back 4

glycolysis (energy creation), glycogenesis (energy storage), hexose monophosphate (HMP) shunt

Front 5

How is pyruvate (produced via glycolysis) used aerobically and anaerobically?

Back 5

Mitochondrial TCA cycle (aerobic) and lactate (anaerobic) via lactate dehydrogenase

Front 6

GLUTs allow transport of glucose. Is this passive or active transport?

Back 6

passive, and so glucose flows down concentration gradient

Front 7

Normal blood glucose concentration is...

Back 7

70-140 mg/dL or 4-8 mM

Front 8

GLUT4 tissue distribution

Back 8

muscle, adipose tissue; this GLUT is recruited to membrane when glucose is available, insulin is the signal that prompts their recruitment (thus it is insulin dependent)

Front 9

GLUT2 tissue distribution

Back 9

Liver, kidney, intestine, pancreatic ß cells

Front 10

What are the 2 irreversible reactions in glycolysis that we need to know (there are 3 total)?

Back 10

Step 1: the sugar trap where hexokinase/glucokinase makes glucose into glucose 6-phosphate

Step 3: the rate-limiting step that uses phosphofructokinase-1 (PFK-1) to make fructose 6-phosphate into fructose 1,6-bisphosphate

Front 11

Hexokinase and glucokinase make glucose into glucose 6-phosphate, why is this important?

Back 11

GLUT is not an active transporter, and so glucose can flow into or out of the cell via this channel, phosphorylating glucose prevents this and forces it to be used in one of the metabolic pathways

Front 12

Where can you find hexokinase and glucokinase?

Back 12

hexokinase is in most tissues, glucokinase is in liver and pancreatic ß cells

Front 13

Glucokinase has a high Km and high Vmax, why is this important (think about where you find glucokinase)?

Back 13

Glucokinase is found in the liver, having a high Km and a high Vmax allows glucokinase to "trap" a large amount of glucose in the liver to prevent hyperglycemia

Front 14

PFK-1 inhibited by

Back 14

high levels of ATP and/or citrate (since you have a lot of ATP, that means you have a lot of energy, so you can slow down glycolysis; high citrate, think lipogenesis since you have enough ATP, thus glucose 6-phosphate can be used by HMP shunt)

Front 15

PFK-1 activated by

Back 15

high levels of AMP or fructose 2,6-bisphosphate (AMP is low energy version of ATP, so you want glycolysis to run to produce energy, fructose 2,6-bisphosphate is produced by PFK-2/FBP-2 which is regulated by I/G ratio)

Front 16

What does it mean that the enzymes in the 3 irreversible reactions of glycolysis are transcriptionally regulated?

Back 16

High insulin upregulates transcription of enzyme mRNA and subsequent protein synthesis, so the more glucose we take into our body, the better we become at catabolizing it

Front 17

3 enzymes that act on pyruvate

Back 17

lactate dehydrogenase to lactate (anaerobic glycolysis in cytosol), pyruvate dehydrogenase (aka PDHC) to acetyl CoA (mitochondria), and pyruvate carboxylase to oxaloacetate (OAA; mitochondria)

Front 18

Pyruvate gets made into acetyl CoA by what enzyme?

Back 18

pyruvate dehydrogenase (PDHC)

Front 19

Pyruvate carboxylase converts pyruvate into...

Back 19

oxaloacetate (OAA)

Front 20

Coenzymes for PDHC

Back 20

TPP, FAD, CoA, NAD+, lipoic acid

Front 21

TPP, FAD, CoA, NAD+, Lipoic Acid (coenzymes for PDHC) have vitamin precursors, what are they in order?

Back 21

thiamine (B1), riboflavin (B2), pantothenate (B5), niacin (B3), lipoic acid as no precursors

Front 22

PDH kinase phosphorylates PDHC, inactivating it. What acts on PDH kinase?

Back 22

NADH, acetyl CoA, and ATP activate PDH, which means PDHC is ultimately inactivated.

Pyruvate deactivates PDH kinase, which lowers phosphorylation of PDHC

Front 23

If PDHC is phosphorylated by PDH kinase, rendering it inactive, what enzyme dephosphorylates it? What ion activates this enzyme?

Back 23

PDH phosphatase; Ca2+

Front 24

Aside from being inactivated by PDH kinase, the products of PDHC (or later pathways) also inactivate it (product inhibition). What are these two products and their significance?

Back 24

NADH accumulates if ETC can't accept more (saturation or because O2 is limited); acetyl CoA accumulates if not used by TCA cycle

this allows pyruvate to be used to make lactate or oxaloacetate

Front 25

TCA cycle is amphibolic, true or false? Define amphibolic.

Back 25

True! It participates in both anabolic and catabolic pathways

Front 26

TCA cycle is regenerative, define regenerative.

Back 26

product becomes substrate for next reaction and is renewed each time cycle is completed

Front 27

What energy is produced in TCA cycle?

Back 27

1 GTP, 3 NADH, 1 FADH2 per complete cycle

Front 28

TCA cycle is always on, but its rate changes. Which state is it found to be higher in activity, fed or fasting?

Back 28

Fed