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MBChB 4 > Biochemistry > Flashcards

Biochemistry Flashcards

1
Q

In a non-starving state, how is glucose metabolised?

A

Glycolysis

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2
Q

What is gluconeogenesis?

A

Synthesis of glucose from pyruvate (end product of glycolysis) Reversal of glycolysis ( uses other enzymes)

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3
Q

What are the steps of glycolysis?

A

1. Glucose → glucose 6-phosphate (G6P)

Enzyme: Hexokinase: in all tissues (inhibited by G6P)

Glucokinase: in β-cells of the pancreas, and liver tissue (inhibited by fructose 6-phosphate)

Requires ATP

2. G6P → fructose 6-phosphate (F6P)

Enzyme: G6P isomerase

3. F6P → fructose 1,6-biphosphate

Enzyme: PKF-1

Requires ATP

4. Fructose 1,6-biphosphate → glyceraldehyde 3-phosphate (GAP)

Enzyme: aldolase

5. GAP → 1,3-Biphosphoglycerate (1,3-BPG)

Enzyme: GAP dehydrogenase

Produces NADH + H+

1,3-BPG → 3-phosphoglycerate

6. Enzyme: phosphoglycerate kinase

Produces ATP

7. 3-phosphoglycerate → 2-phosphoglycerate

Enzyme: phosphoglycerate mutase

8. 2-phosphoglycerate → phosphoenolpyruvate (PEP)

Enzyme: enolase

9. PEP → pyruvate

Enzyme: pyruvate kinase

Produces ATP

Stimulated by fructose 1,6-biphosphate

Inhibited by ATP and alanine

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4
Q

What is glycolysis? What does it yield?

A

A metabolic pathway that breaks down glucose by substrate-level phosphorylation and oxidation, yielding 2 pyruvate molecules and 2 ATP.

2 ATP molecules are consumed in this process

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5
Q

What regulates glycolysis?

A

Hexokinase enzyme:

Role: converts glucose -> G6P

Stimulated by insulin

Inhibited by: G6P formation / glucagon

Phosphofructokinase 1:

Role: Convert F6P -> Fructose 1,6 phosphate

Stimulated by: AMP, Frctuose2,6 phosphate (feed forward mechanism, insulin

Inhibited by: ATP (as energy is plentiful), Citrate (indicated glycolysis intermediates, therefore slows glycolysis), glucagon action in liver

Pyruvate kinase:

Converts PEP to pyruvate

Stimulated by: Fructose 1,5 phosphate (glycolysis intermediate

Inhibited: ATP (indicates plnety of energy), Alanine ( indicates biosynthesis)

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6
Q

What is phosphofuctase 2 and what is its role?

A

It is a bi-directional enzyme that may act as a phosphatase or a kinase

As a kinase –> it creates fuctose 2,6 phosphate which stimulates glycolysis

As a phosphatase –> stimulates gluconeognesis and reduces glycolysis

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7
Q

What are the phosphatase and kinases domains of phosphofructokinase -2

A

Phosphatase domain: Fructose-1,6-bisphosphatase

Kinase domain: Phosphofructokinase-1 (PFK-1)

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8
Q

Under what circumstances does phosphofructoasekinase 1 stimulate glycolysis?

A

Pro-prandial phase

(Acts as a feed forward mechanism)

Postprandial state:

High blood glucose → increased circulating insulin levels (indicate a high abundance of blood glucose available for glycolysis) → decreased levels of cAMP → decreased PKA activity → inhibition of FBPase-2 (phosphatase) and stimulation of PFK-2 domain (kinase)→ increased production of F-2,6-P2 → F-2,6-P2 activates PFK-1→ more glycolysis + less gluconeogenesis

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9
Q

What determines of phosphofructokinase acts as a kinase or phosphatase?

A

Activity of Protein Kinase A

Post-prandial state: PKA is inhibited by low cAMP

Starving state: PKA activated by high cAMP

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10
Q

Under what circumstances of phosphofructokinase inhibit glycolysis

A

Fasting State

Fasting state: low blood glucose → increased circulating glucagon levels → increased levels of cAMP → increased protein kinase A (PKA) activity → stimulation of FBPase-2 and inhibition of PFK-2 domain → decreased production of F-2,6-P2 → less glycolysis + more gluconeogenesis

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11
Q

Does glycolysis occur in anaerobic conditions?

A

Yes

Pyruvate may be used in the kreb cycle or gluconeogenesis

Pyruvate is the final product of glycolysis - which may be converted into lactic acid in anaerobic respiration

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12
Q

How may pyruvate be metabolised?

A

Lactic acid -> Gluconeogenesis (anaerobic respiration)

Acetyl Co-A -> Krebs cycle (aerobic respiration)

Oxaloacetate -> involved in aerobic and anaerobic resp

Alanine -> Gluconeogenesis

liver converts pyruvate -> alanine via cahill cycle for gluconeogenesis -> produces ammonia (sign of anaerobic resp)

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13
Q

What is gluconeogenesis?

A

A series of metabolic events that allows for the production of glucose from noncarbohydrate precursors.

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14
Q

When is gluconeogenesis used?

A

During fasting

After glucogen stores have been used (e.g. 1-3 days after fasting)

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15
Q

What substates can be used for gluconeogenesis?

A

Amino acids

Lactate (cori cycle)

Fatty acids (e.g. propional Co A)

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16
Q

What is the pentose phosphate pathway?

A

Alternative metabolic pathway that creates ribose and NADPH from glucose 6 phosphate which may converted into other products

17
Q

Function of pentose phosphate pathway?

A

Production of ribose sugar for DNA and RNA

Production of NADPH required for:

  • fatty acid synthesis
  • cholesterol synthesis
  • reduction of glutathione
18
Q

Where is gluconeogenesis carried out?

A

Primarily carried out in the liver

Renal cortex

Intestinal epithelium

Skeletal muscle cannot participate in gluconeogenesis due to absent glucose-6-phosphatase

19
Q

What is a monosaccharide?

A

A simple carbohydrate that cannot be broken down any further

e.g. glucose, fructose and galatose

20
Q

What is a disaccharide?

A

Two mono-saccharides bonded by a glycosidic bond

e.g. sucrose, maltose, lactose

21
Q

What is a polysaccharide?

A

Many monosaccharides bonded together?

e.g. starch, glycogen

22
Q

What are the two forms of glycosidic bond and why is this important?

A

1,4 - alpha glycosidic bond (OH group below the plane of the ring)

1,4 - beta glycosidic bond (OH group above the plane of the ring)

Lactase is the only enzyme in the body capable of cleaving a 1,4 beta glycosidic bond

23
Q

What are examples of sugars with a 1,4- beta glycosidic bond?

A

Lactose

Cellulose

24
Q

What monosaccharides make up maltose?

A

Glucose + Glucose

25
Q

What monosacchardies make up lactose?

A

Galatose + glucose

26
Q

What monosaccharides make up sucrose?

A

Glucose + fructose

27
Q

How do intestines absorb carbohydrates?

A

Absorb them as monosaccharides

Therefore: carbohydrates need to be broken down

28
Q

What enzymes are important for digestion of carbohydrates?

A

Alpha-amylase: Mouth + Pancreas

Lactase: Intestinal microvilli

Surcase: Interstinal microvilli

Maltase: Intestinal microvilli

29
Q

How is glucose abosrbed in the body?

A
  1. GLUT receptor on cells
  2. Na+ Glucose transporter in intestinal epithelium and proximal renal tubule

- SGLT1 in intestinal cells

- SGLT2 in proximal renal tubule cells

30
Q

How is glucose abosrbed in intestinal epithelial cells?

A

Sodium-dependent glucose cotransporter 1 (SGLT1)

Transporter on the luminal side of mucosa cells

Sodium concentration gradient, which is maintained by basal Na+/K+ ATPase by transporting sodium out of the cell (secondary active transport).

SGLT1 also absorbs galatose

31
Q

How is glucose absorbed at the kidneys?

A

Glucose is filtered into the kidneys at the glomerulus and must be reabsorbed

Complete reabsorption in the proximal tubules via 2 types of SGLT → urine normally glucose free

SGLT2: reabsorbs ∼ 98% of urinary glucose in the proximal convoluted tubule (PCT)

One molecule of glucose is absorbed together with one molecule of sodium

SGLT1: reabsorbs the remaining glucose (∼ 2%) as well as galactose in the PST

One molecule of glucose is absorbed together with two molecules of sodium.

Fructose is absorbed via GLUT5 (glucose transporter).

Reabsorption also relies on a sodium concentration gradient via Na+/K+ ATPase.

32
Q

What is the function of GLUT1 and where is it found?

A

Location: Most human cells, RBC, CNS, Cornea, Placenta

Function: Allows entry of glucose into cell

33
Q

What is the function of GLUT2

A
  1. Transports all monosaccharide from the basolateral membrane of enterocytes into the blood
  2. Measures levels of glucose in pancreatic islet Beta cells
  3. Bidirectional transport of glucose in hepatocytes -> excretion of glucose in gluconeogenesis and takes in glucose for glycolysis
34
Q

Where is GLUT 2 receptor located?

A

Hepatocytes

Pancreatic β-islet cells

Kidney

Small intestine

35
Q

What is the function of GLUT4?

A

Very important role in glucose metabolism

Insulin stimulates incorportation of GLUT 4 into cell membrane –> allows glucose entry into cell

36
Q

What is the only insulin dependent GLUT receptor

A

GLUT4

37
Q

What is the function of GLUT5?

A

Fructose transporter

Located: small intestine enterocytes + spermatocytes

38
Q
A

MBChB 4 (9 decks)

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