Biochemistry 9 Mcat

Front 1

The hyperketonemia in diabetic ketoacidosis is the result of insulin deficiency and unregulated glucagon secretion from α-cells of the pancreas. Circulating glucagon stimulates the adipose tissue to release fatty acids stored in triglycerides. The free fatty acids enter the circulation and are taken up primarily by the liver where they undergo fatty acid oxidation to acetyl-CoA. Normally, acetyl CoA is completely oxidized to CO2 and water in the TCA cycle.

Back 1

However, the level of fatty acid oxidation is in excess of the livers' ability to fully oxidize the excess acetyl CoA and, thus, the compound is diverted into the ketogenesis pathway. The ketones (ketone bodies) are β-hydroxybutyrate and acetoacetate with β-hydroxybutyrate being the most abundant. Acetoacetate will spontaneously (non-enzymatic) decarboxylate to acetone. Acetone is volatile and is released from the lungs giving the characteristic sweet smell to the breath of someone with hyperketonemia. The ketones are released into the circulation and because they are acidic, lower the pH of the blood resulting in metabolic acidosis.

Front 2

Glycolysis occurs in the cytoplasm of all cells, and does not require _____. It yields __ ATP per molecule of glucose.

Back 2

Glycolysis occurs in the cytoplasm of all cells, and does not require oxygen. It yields 2 ATP per molecule of glucose.

Front 3

Glucokinase (only in liver and pancreas), converts glucose to _____. It is present in pancreatic β-islet cells as part of the glucose sensor. Phosphorylating glucose keeps it in the cell and does not let it exit through a GLUT transporter.

Back 3

glucose-6-phosphate

Front 4

______ converts glucose to G-6-P in peripheral tissues

Back 4

Hexokinase converts glucose to G-6-P in peripheral tissues

Front 5

Phosphofructokinase F-6-P to F-1,6-BP (rate limiting step) of glycolysis.

-It is activated by AMP and inhibited by ATP and citrate, why?

Back 5

The cell should turn on when ATP is needed, and turn off when energy is sufficient.

Front 6

Glyceraldehyde-3-Phosphate dehydrogenase produces NADH, which can feed into the ETC

(GA3P)-> 1,3-bisphosphoglycerate

Back 6

3-phosphoglycerate kinase and pyruvate kinase each perform substrate-level phosphorylation, ADP->ATP (2 ATP produced)

Front 7

DHAP (dihydroxyacetone phosphate) can isomerize to G-3-P which can convert to glycerol. Glycerol is the backbone of TAG's.

Back 7

In RBC's, the only source of ATP is glycolysis (no mitochondria)

Front 8

If oxygen or mitochondria are absent (RBC), the NADH produced in glycolysis is oxidized by lactate dehydrogenase. Pyruvate is converted to _____. Why is this significant?

Back 8

Lactate; this is significant because w/o this, there'd be no NAD+ and there'd be no e- carriers available to take e- for glycolysis.

Front 9

2,3-BPG can bind to RBC's and ________ its affinity for oxygen. Fetal hemoglobin does not bing 2,3-BPG; which keeps its affinity ____ for oxygen.

Back 9

2,3-BPG can bind to RBC's and decrease its affinity for oxygen. Fetal hemoglobin does not bing 2,3-BPG; which keeps its affinity high for oxygen.

Front 10

What does pyruvate dehydrogenase do?

Back 10

It is a complex of enzymes which convert pyruvate to acetyl-CoA.

-It is an irreversible reaction and thus acetyl-CoA can't go back to pyruvate (can't make sugars from fat)

-Stimulated by insulin (stores glucose as fat), inhibited by acetyl-CoA

Front 11

Key Concept: B/c DHAP and glyceraldehyde (products of fructose metabolism), are downstream from the key regulatory and rate-limiting enzyme of glycolysis, a high-fructose drink supplies a quick source of energy in both aerobic and anaerboic cells

Back 11

Key Concept: The glycogen in the liver and in skeletal muscle serve two quite different roles. Liver glycogen is broken down to maintain a constant level of glucose in the blood; muscle glycogen is broken down to provide glucose to the muscle during vigorous exercise

Front 12

Glycogenesis is glycogen synthesis using two main enzymes.

-______ synthase, which createsα-1,4 glycosidic links. Activated by: insulin. Inhibited by: epinephrine and glucagon

-_____ enzyme: moves oligoglucose to create new brance in aα-1,6 glycosidic link

Back 12

-Glycogen synthase, which creates α-1,4 glycosidic links. Activated by: insulin. Inhibited by: epinephrine and glucagon

-Branching enzyme: moves oligoglucose to create new brance in a α-1,6 glycosidic link

Front 13

Glycogenolysis is the breakdown of glycogen using two main enzymes:

-Glycogen __________: cleave α-1,4 bond in glycogen to glucose 1-phosphate. Activated by glucagon in liver, and AMP or epinephrine in muscle

-_______ enzyme: breaks α-1,6 glycosidic link and adds to chain and makes aα-1,4 link.

Back 13

-Glycogen phosphorylase: cleave α-1,4 bond in glycogen to glucose 1-phosphate. Activated by glucagon in liver, and AMP or epinephrine in muscle (insulin activate PP1 and it dephosphorylates to inactivate)

-Debranching enzyme: breaks α-1,6 glycosidic link and adds to chain and makes a α-1,4 link.

Front 14

Gluconeogenesis occurs in both ____ and ____, predominantly in the liver. It is the reverse of glycolysis, but uses a few different enzyme for the irreversible steps of glycolysis.

Back 14

Gluconeogenesis occurs in both cytoplasm and mitochondria, predominantly in the liver. It is the reverse of glycolysis, but uses a few different enzyme for the irreversible steps of glycolysis.

Front 15

Pyruvate carboxylase converts pyruvate to OAA, which is converted to PEP

Back 15

Front 16

-Fructose-1,6-bisphosphatase converts F-1,6-BP to F-6-P, bypassing phophofructokinase.

-Glucose-6-phosphatase converts G-6-P to free glucose, bypassing glucokinase. (not hexakinase, glucneogenesis does not occur in muscle)

Back 16

Front 17

Key Concept: Insulin acts to lower blood sugar levels; the counter regulatory hormones are glucagon, epinephrine, cortisol, and growth hormone (all can increase blood sugar level by stimulating glycolysis (glycogenolysis) and gluconeogenesis)

Back 17

Key Concept: B/c gluconeogenesis requires acteyl-CoA, it is inextricably linked to FA oxidation- the source of actely-CoA cannot be glycolyis because this would just burn glucose that is being generated in gluconeogenesis.

Front 18

Low blood sugar can cause release of TAG from adipose tissue. Glycerol->Glycerol-3-phosphate-> which enters glycolysis.

-Acteyl-CoA's from B-oxidation of FA can also form ketone bodies which contributes to energy source in times of starvation.

Back 18

Note: Odd-chain FA can contribute to glucose because propinyl- CoA can convert to Succinyl-CoA and enter CAC.

Front 19

The pentose phosphate pathway (PPP) occurs in the _____ of cells. It generates ____ and sugars for nucleotide biosynthesis (derived from ribulose-5-phosphate)

Back 19

The pentose phosphate pathway (PPP) occurs in the cytoplasm of cells. It generates NADPH and sugars for nucleotide biosynthesis (derived from ribulose-5-phosphate)

Front 20

The second part (non-oxidative phase) of the PPP creates a pool of sugars (F-6-P and G-3-P). These can feed back into glycolysis.

Back 20

Key Concept: of all the enzymes the MCAT is most likely to test you on, the rate-limiting enzymes for each process are at the top of the list.

Front 21

Key Concept: NADPH and NADH are not the same thing. NAD+ is an e- carrier; NADPH is used in biosynthesis, in the immune system and to help prevent oxidative damage (reduces glutathione)

Back 21

Free radicals and superoxides cause DNA damage, or weaken membranes which cause lyses. Glutathione is a reducing agent which helps reverse radical formation.

Front 22

The rate limiting step of PPP is G-6-P dehydrogenase. It is activated by NADP+ and insulin, and inhibited by NADPH.

Back 22

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